Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Amino Acid Metabolism, Inborn Errors: Disorders affecting amino acid metabolism. The majority of these disorders are inherited and present in the neonatal period with metabolic disturbances (e.g., ACIDOSIS) and neurologic manifestations. They are present at birth, although they may not become symptomatic until later in life.Lipid Metabolism, Inborn Errors: Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.Neonatal Screening: The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates (INFANT, NEWBORN) from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic.Purine-Pyrimidine Metabolism, Inborn ErrorsSteroid Metabolism, Inborn Errors: Errors in metabolic processing of STEROIDS resulting from inborn genetic mutations that are inherited or acquired in utero.Carbohydrate Metabolism, Inborn ErrorsUrea Cycle Disorders, Inborn: Rare congenital metabolism disorders of the urea cycle. The disorders are due to mutations that result in complete (neonatal onset) or partial (childhood or adult onset) inactivity of an enzyme, involved in the urea cycle. Neonatal onset results in clinical features that include irritability, vomiting, lethargy, seizures, NEONATAL HYPOTONIA; RESPIRATORY ALKALOSIS; HYPERAMMONEMIA; coma, and death. Survivors of the neonatal onset and childhood/adult onset disorders share common risks for ENCEPHALOPATHIES, METABOLIC, INBORN; and RESPIRATORY ALKALOSIS due to HYPERAMMONEMIA.Brain Diseases, Metabolic, Inborn: Brain disorders resulting from inborn metabolic errors, primarily from enzymatic defects which lead to substrate accumulation, product reduction, or increase in toxic metabolites through alternate pathways. The majority of these conditions are familial, however spontaneous mutation may also occur in utero.Argininosuccinic Aciduria: Rare autosomal recessive disorder of the urea cycle which leads to the accumulation of argininosuccinic acid in body fluids and severe HYPERAMMONEMIA. Clinical features of the neonatal onset of the disorder include poor feeding, vomiting, lethargy, seizures, tachypnea, coma, and death. Later onset results in milder set of clinical features including vomiting, failure to thrive, irritability, behavioral problems, or psychomotor retardation. Mutations in the ARGININOSUCCINATE LYASE gene cause the disorder.Hyperammonemia: Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).Smith-Lemli-Opitz Syndrome: An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and INTELLECTUAL DISABILITY.Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus.Infant, Newborn: An infant during the first month after birth.Homogentisate 1,2-Dioxygenase: A mononuclear Fe(II)-dependent oxygenase, this enzyme catalyzes the conversion of homogentisate to 4-maleylacetoacetate, the third step in the pathway for the catabolism of TYROSINE. Deficiency in the enzyme causes ALKAPTONURIA, an autosomal recessive disorder, characterized by homogentisic aciduria, OCHRONOSIS and ARTHRITIS. This enzyme was formerly characterized as EC and EC Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of CYSTATHIONINE BETA-SYNTHASE and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall slender habitus, SCOLIOSIS, arachnodactyly, MUSCLE WEAKNESS, genu varus, thin blond hair, malar flush, lens dislocations, an increased incidence of MENTAL RETARDATION, and a tendency to develop fibrosis of arteries, frequently complicated by CEREBROVASCULAR ACCIDENTS and MYOCARDIAL INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, p979)Candidiasis, Chronic Mucocutaneous: A clinical syndrome characterized by development, usually in infancy or childhood, of a chronic, often widespread candidiasis of skin, nails, and mucous membranes. It may be secondary to one of the immunodeficiency syndromes, inherited as an autosomal recessive trait, or associated with defects in cell-mediated immunity, endocrine disorders, dental stomatitis, or malignancy.Pyruvate Metabolism, Inborn Errors: Hereditary disorders of pyruvate metabolism. They are difficult to diagnose and describe because pyruvate is a key intermediate in glycolysis, gluconeogenesis, and the tricarboxylic acid cycle. Some inherited metabolic disorders may alter pyruvate metabolism indirectly. Disorders in pyruvate metabolism appear to lead to deficiencies in neurotransmitter synthesis and, consequently, to nervous system disorders.alpha-Galactosidase: An enzyme that catalyzes the hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-galactosides including galactose oligosaccharides, galactomannans, and galactolipids.Fabry Disease: An X-linked inherited metabolic disease caused by a deficiency of lysosomal ALPHA-GALACTOSIDASE A. It is characterized by intralysosomal accumulation of globotriaosylceramide and other GLYCOSPHINGOLIPIDS in blood vessels throughout the body leading to multi-system complications including renal, cardiac, cerebrovascular, and skin disorders.Australian Capital Territory: A territory of Australia consisting of Canberra, the national capital and surrounding land. It lies geographically within NEW SOUTH WALES and was established by law in 1988.Ornithine Carbamoyltransferase Deficiency Disease: An inherited urea cycle disorder associated with deficiency of the enzyme ORNITHINE CARBAMOYLTRANSFERASE, transmitted as an X-linked trait and featuring elevations of amino acids and ammonia in the serum. Clinical features, which are more prominent in males, include seizures, behavioral alterations, episodic vomiting, lethargy, and coma. (Menkes, Textbook of Child Neurology, 5th ed, pp49-50)Argininosuccinic Acid: This amino acid is formed during the urea cycle from citrulline, aspartate and ATP. This reaction is catalyzed by argininosuccinic acid synthetase.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Isovaleryl-CoA Dehydrogenase: A mitochondrial flavoprotein, this enzyme catalyzes the oxidation of 3-methylbutanoyl-CoA to 3-methylbut-2-enoyl-CoA using FAD as a cofactor. Defects in the enzyme, is associated with isovaleric acidemia (IVA).Hypophosphatasia: A genetic metabolic disorder resulting from serum and bone alkaline phosphatase deficiency leading to hypercalcemia, ethanolamine phosphatemia, and ethanolamine phosphaturia. Clinical manifestations include severe skeletal defects resembling vitamin D-resistant rickets, failure of the calvarium to calcify, dyspnea, cyanosis, vomiting, constipation, renal calcinosis, failure to thrive, disorders of movement, beading of the costochondral junction, and rachitic bone changes. (From Dorland, 27th ed)Methylmalonic Acid: A malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA.Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures.Brain Diseases, Metabolic: Acquired or inborn metabolic diseases that produce brain dysfunction or damage. These include primary (i.e., disorders intrinsic to the brain) and secondary (i.e., extracranial) metabolic conditions that adversely affect cerebral function.Hydroxocobalamin: Injectable form of VITAMIN B 12 that has been used therapeutically to treat VITAMIN B 12 DEFICIENCY.Pentanoic AcidsMethylmalonyl-CoA Mutase: An enzyme that catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA by transfer of the carbonyl group. It requires a cobamide coenzyme. A block in this enzymatic conversion leads to the metabolic disease, methylmalonic aciduria. EC Acting on CH-CH Group Donors: A subclass of enzymes which includes all dehydrogenases acting on carbon-carbon bonds. This enzyme group includes all the enzymes that introduce double bonds into substrates by direct dehydrogenation of carbon-carbon single bonds.Carnitine: A constituent of STRIATED MUSCLE and LIVER. It is an amino acid derivative and an essential cofactor for fatty acid metabolism.Metal Metabolism, Inborn ErrorsMetabolism: The chemical reactions that occur within the cells, tissues, or an organism. These processes include both the biosynthesis (ANABOLISM) and the breakdown (CATABOLISM) of organic materials utilized by the living organism.Fructose Metabolism, Inborn Errors: Inherited abnormalities of fructose metabolism, which include three known autosomal recessive types: hepatic fructokinase deficiency (essential fructosuria), hereditary fructose intolerance, and hereditary fructose-1,6-diphosphatase deficiency. Essential fructosuria is a benign asymptomatic metabolic disorder caused by deficiency in fructokinase, leading to decreased conversion of fructose to fructose-1-phosphate and alimentary hyperfructosemia, but with no clinical dysfunction; may produce a false-positive diabetes test.GlutaratesMaple Syrup Urine Disease: An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids (AMINO ACIDS, BRANCHED-CHAIN). These metabolites accumulate in body fluids and render a "maple syrup" odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. (From Adams et al., Principles of Neurology, 6th ed, p936)Amidinotransferases: Enzymes of a subclass of TRANSFERASES that catalyze the transfer of an amidino group from donor to acceptor. EC 2.1.4.Metabolic Diseases: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed)Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Porphyria, Erythropoietic: An autosomal recessive porphyria that is due to a deficiency of UROPORPHYRINOGEN III SYNTHASE in the BONE MARROW; also known as congenital erythropoietic porphyria. This disease is characterized by SPLENOMEGALY; ANEMIA; photosensitivity; cutaneous lesions; accumulation of hydroxymethylbilane; and increased excretion of UROPORPHYRINS and COPROPORPHYRINS.Glutaryl-CoA Dehydrogenase: A flavoprotein enzyme that is responsible for the catabolism of LYSINE; HYDROXYLYSINE; and TRYPTOPHAN. It catalyzes the oxidation of GLUTARYL-CoA to crotonoyl-CoA using FAD as a cofactor. Glutaric aciduria type I is an inborn error of metabolism due to the deficiency of glutaryl-CoA dehydrogenase.Hyperargininemia: A rare autosomal recessive disorder of the urea cycle. It is caused by a deficiency of the hepatic enzyme ARGINASE. Arginine is elevated in the blood and cerebrospinal fluid, and periodic HYPERAMMONEMIA may occur. Disease onset is usually in infancy or early childhood. Clinical manifestations include seizures, microcephaly, progressive mental impairment, hypotonia, ataxia, spastic diplegia, and quadriparesis. (From Hum Genet 1993 Mar;91(1):1-5; Menkes, Textbook of Child Neurology, 5th ed, p51)Failure to Thrive: A condition of substandard growth or diminished capacity to maintain normal function.Iron Metabolism Disorders: Disorders in the processing of iron in the body: its absorption, transport, storage, and utilization. (From Mosby's Medical, Nursing, & Allied Health Dictionary, 4th ed)Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase: An NAD-dependent 3-hydroxyacyl CoA dehydrogenase that has specificity for acyl chains containing 8 and 10 carbons.Alkaptonuria: An inborn error of amino acid metabolism resulting from a defect in the enzyme HOMOGENTISATE 1,2-DIOXYGENASE, an enzyme involved in the breakdown of PHENYLALANINE and TYROSINE. It is characterized by accumulation of HOMOGENTISIC ACID in the urine, OCHRONOSIS in various tissues, and ARTHRITIS.Rare Diseases: A large group of diseases which are characterized by a low prevalence in the population. They frequently are associated with problems in diagnosis and treatment.Citrullinemia: A group of diseases related to a deficiency of the enzyme ARGININOSUCCINATE SYNTHASE which causes an elevation of serum levels of CITRULLINE. In neonates, clinical manifestations include lethargy, hypotonia, and SEIZURES. Milder forms also occur. Childhood and adult forms may present with recurrent episodes of intermittent weakness, lethargy, ATAXIA, behavioral changes, and DYSARTHRIA. (From Menkes, Textbook of Child Neurology, 5th ed, p49)Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Multiple Acyl Coenzyme A Dehydrogenase Deficiency: An autosomal recessive disorder of fatty acid oxidation, and branched chain amino acids (AMINO ACIDS, BRANCHED-CHAIN); LYSINE; and CHOLINE catabolism, that is due to defects in either subunit of ELECTRON TRANSFER FLAVOPROTEIN or its dehydrogenase, electron transfer flavoprotein-ubiquinone oxidoreductase (EC Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Adenylosuccinate Lyase: An enzyme that, in the course of purine ribonucleotide biosynthesis, catalyzes the conversion of 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole to 5'-phosphoribosyl-4-carboxamide-5-aminoimidazole and the conversion of adenylosuccinic acid to AMP. EC Dehydrogenase: A flavoprotein oxidoreductase that has specificity for medium-chain fatty acids. It forms a complex with ELECTRON TRANSFERRING FLAVOPROTEINS and conveys reducing equivalents to UBIQUINONE.Pyruvate Dehydrogenase Complex Deficiency Disease: An inherited metabolic disorder caused by deficient enzyme activity in the PYRUVATE DEHYDROGENASE COMPLEX, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. Two clinical forms are recognized: neonatal and juvenile. The neonatal form is a relatively common cause of lactic acidosis in the first weeks of life and may also feature an erythematous rash. The juvenile form presents with lactic acidosis, alopecia, intermittent ATAXIA; SEIZURES; and an erythematous rash. (From J Inherit Metab Dis 1996;19(4):452-62) Autosomal recessive and X-linked forms are caused by mutations in the genes for the three different enzyme components of this multisubunit pyruvate dehydrogenase complex. One of the mutations at Xp22.2-p22.1 in the gene for the E1 alpha component of the complex leads to LEIGH DISEASE.Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.Ornithine-Oxo-Acid Transaminase: A pyridoxal phosphate enzyme that catalyzes the formation of glutamate gamma-semialdehyde and an L-amino acid from L-ornithine and a 2-keto-acid. EC Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Neuroaxonal Dystrophies: A nonspecific term referring both to the pathologic finding of swelling of distal portions of axons in the brain and to disorders which feature this finding. Neuroaxonal dystrophy is seen in various genetic diseases, vitamin deficiencies, and aging. Infantile neuroaxonal dystrophy is an autosomal recessive disease characterized by arrested psychomotor development at 6 months to 2 years of age, ataxia, brain stem dysfunction, and quadriparesis. Juvenile and adult forms also occur. Pathologic findings include brain atrophy and widespread accumulation of axonal spheroids throughout the neuroaxis, peripheral nerves, and dental pulp. (From Davis & Robertson, Textbook of Neuropathology, 2nd ed, p927)Hyperoxaluria, Primary: A genetic disorder characterized by excretion of large amounts of OXALATES in urine; NEPHROLITHIASIS; NEPHROCALCINOSIS; early onset of RENAL FAILURE; and often a generalized deposit of CALCIUM OXALATE. There are subtypes classified by the enzyme defects in glyoxylate metabolism.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Homozygote: An individual in which both alleles at a given locus are identical.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Renal Tubular Transport, Inborn Errors: Genetic defects in the selective or non-selective transport functions of the KIDNEY TUBULES.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Argininosuccinate Lyase: An enzyme of the urea cycle which splits argininosuccinate to fumarate plus arginine. Its absence leads to the metabolic disease ARGININOSUCCINIC ACIDURIA in man. EC The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Uroporphyrinogen III Synthetase: An enzyme that catalyzes the cyclization of hydroxymethylbilane to yield UROPORPHYRINOGEN III and water. It is the fourth enzyme in the 8-enzyme biosynthetic pathway of HEME, and is encoded by UROS gene. Mutations of UROS gene result in CONGENITAL ERYTHROPOIETIC PORPHYRIA.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Tandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Phlebotomy: The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda.Critical Pathways: Schedules of medical and nursing procedures, including diagnostic tests, medications, and consultations designed to effect an efficient, coordinated program of treatment. (From Mosby's Medical, Nursing & Allied Health Dictionary, 4th ed)Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Blood Specimen Collection: The taking of a blood sample to determine its character as a whole, to identify levels of its component cells, chemicals, gases, or other constituents, to perform pathological examination, etc.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Diet, Protein-Restricted: A diet that contains limited amounts of protein. It is prescribed in some cases to slow the progression of renal failure. (From Segen, Dictionary of Modern Medicine, 1992)Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Urea: A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC The magnitude of INBREEDING in humans.Glycolysis: A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.Acyl-CoA Dehydrogenases: Enzymes that catalyze the first step in the beta-oxidation of FATTY ACIDS.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Technology Assessment, Biomedical: Evaluation of biomedical technology in relation to cost, efficacy, utilization, etc., and its future impact on social, ethical, and legal systems.Kinetics: The rate dynamics in chemical or physical systems.Vitamin B 12: A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Intellectual Disability: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.Liver Diseases: Pathological processes of the LIVER.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)Heterozygote: An individual having different alleles at one or more loci regarding a specific character.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Immunologic Deficiency Syndromes: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Carbon: A nonmetallic element with atomic symbol C, atomic number 6, and atomic weight [12.0096; 12.0116]. It may occur as several different allotropes including DIAMOND; CHARCOAL; and GRAPHITE; and as SOOT from incompletely burned fuel.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Lactates: Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.Arginine: An essential amino acid that is physiologically active in the L-form.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.

*  Inborn errors of metabolism: Classification

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*  14-Rinaldo-Newborn Screening for Inborn Errors of Metabolism in the 21st Century -

Home // Store // 14-Rinaldo-Newborn Screening for Inborn Errors of Metabolism in the 21st Century ... 14-Rinaldo-Newborn Screening for Inborn Errors of Metabolism in the 21st Century. * ... 14 Rinaldo Newborn Screening for Inborn Errors of Metabolism in the 21st Century ... 14 13001 Newborn Screening for Inborn Errors of Metabolism in the 21st Century ...

*  Screening for inborn errors of metabolism among newborns with...

Screening for inborn errors of metabolism among newborns with metabolic disturbance and/or neurological manifestations without ... Screening for inborn errors of metabolism among newborns with metabolic disturbance and/or neurological manifestations without ... The selection of 9% of the studied cases for outpatient follow-up confirms that Inborn Errors of Metabolism must be suspected ...

*  Gene Therapy to Heal Scar Tissue

Inborn Errors of Metabolism. Inborn errors of metabolism are genetic disorders that hamper the body s metabolism resulting in ... DNA Finger Printing Reiki and Pranic Healing Genetic Testing of Diseases Pancreas Weaver Syndrome Inborn Errors of Metabolism ...

*  Simultaneous occurrence of xanthine oxidase and sulfite oxidase deficiency. A molybdenum dependent inborn error of metabolism?

Simultaneous occurrence of xanthine oxidase and sulfite oxidase deficiency. A molybdenum dependent inborn error of metabolism ...

*  GTA-Glyceryltriacetate for Canavan Disease - Full Text View -

Genetic Diseases, Inborn. Metabolism, Inborn Errors. Metabolic Diseases. processed this record on September ... Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases. Nervous System ...

*  The Effect of Diflunisal on Familial Transthyretin Amyloidosis - Full Text View -

Genetic Diseases, Inborn. Metabolism, Inborn Errors. Diflunisal. Anti-Inflammatory Agents, Non-Steroidal. Analgesics, Non- ...

*  AMPED Outcomes Registry of Post-ED Pain Management - Full Text View -

Purine-Pyrimidine Metabolism, Inborn Errors. Metabolism, Inborn Errors. Genetic Diseases, Inborn. Metabolic Diseases. Nervous ...

*  Inherited Metabolic Disease Clinic | Children's Hospital & Medical Center

The Inherited Metabolic Disease Clinic at Children's Hospital & Medical Center provides specialized medical expertise for the diagnosis and treatment of pediatric inherited metabolic diseases in Nebraska and the surrounding region. Inherited metabolic diseases are genetic disorders of metabolism, also known as inborn errors of metabolism.

*  Rajiv Gandhi Centre for Biotechnology

RGCB is looking for a Program Scientist to lead and support development of mass spectrometry (MS) based clinical biochemical assays. This is an exciting opportunity to join the RGCB Medical Laboratory Services Program. The Program Scientist will be primarily responsible for establishing MS based clinical assays for Inherited Metabolic Diseases, Newborn Screening Services, Endocrine markers, stone analysis (FT-IR) and an Anti-TNF therapeutic drug monitoring service. The Program Scientist will devote 70% of time developing the above described and related assays and 30% time teaching and training personnel and students.. ...

*  Learn more about Metabolic defects | (e) Science News

in two of the genes have already been implicated in other rare metabolic disorders also involved in cell recycling, while ... . A long-term goal is to use these findings to determine how this metabolic defect affects structures within the brain ...

Journal of Inherited Metabolic Disease: The Journal of Inherited Metabolic Disease is a peer-reviewed medical journal covering inherited metabolic disorders. It was established in 1978 and is the official journal of the Society for the Study of Inborn Errors of Metabolism.Lysinuric protein intoleranceNeutral lipid storage disease: Neutral lipid storage disease (also known as Chanarin–Dorfman syndrome) is an autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes, muscle, liver, fibroblasts, and other tissues.Freedberg, et al.HyperammonemiaIndex of energy articles: This is an index of energy articles.Lipotoxicity: Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle.Hyperphenylalaninemia: (also includes non-classic PKU)Smith–Lemli–Opitz syndromeAutorefractor: An autorefractor or automated refractor is a computer-controlled machine used during an eye examination to provide an objective measurement of a person's refractive error and prescription for glasses or contact lenses. This is achieved by measuring how light is changed as it enters a person's eye.Low-sulfur diet: A low-sulfur diet is a diet with reduced sulfur content. Sulfur containing compounds may also be referred to as thiols or mercaptans.Chronic mucocutaneous candidiasisBeano (dietary supplement): Beano is an enzyme-based dietary supplement that is used to reduce gas in the digestive tract, thereby improving digestion and reducing bloating, discomfort, and flatulence caused by gas. It contains the enzyme alpha-galactosidase.Fabry disease: (ILDS E75.25)Giralang, Australian Capital TerritoryOrnithine transcarbamylase: Ornithine transcarbamylase (OTC) (also called ornithine carbamoyltransferase) is an enzyme that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (Pi). In plants and microbes, OTC is involved in arginine (Arg) biosynthesis, whereas in mammals it is located in the mitochondria and is part of the urea cycle.Argininosuccinic acidSilent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GIHypophosphatasiaMethylmalonic acidPrescription cascade: Prescription cascade refers to the process whereby the side effects of drugs are misdiagnosed as symptoms of another problem resulting in further prescriptions and further side effects and unanticipated drug interactions. This may lead to further misdiagnoses and further symptoms.HydroxocobalaminIsovaleric acidemiaMethylmalonyl-CoASystemic primary carnitine deficiencySotolonArginine:glycine amidinotransferaseGlucose transporterErythropoietic porphyriaGlutaryl-CoA dehydrogenase: Glutaryl-CoA dehydrogenase (GCDH) is an enzyme encoded by the GCDH gene on chromosome 19. The protein belongs to the acyl-CoA dehydrogenase family (ACD).Argininemia: Argininemia, also called arginase deficiency, is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood.Flux (metabolism): Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway.NitisinoneRDCRN Contact Registry: The Rare Diseases Clinical Research Network (RDCRN) Contact Registry is an international patient contact registry sponsored by the National Institutes of Health. This registry collects basic data (i.CitrullinemiaColes PhillipsMatrix model: == Mathematics and physics ==AdenylosuccinateMedium-chain acyl-coenzyme A dehydrogenase deficiencyOrnithine aminotransferase deficiency: Ornithine aminotransferase deficiency (also known as gyrate atrophy of the choroid and retina) is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase. Biochemically, it can be detected by elevated levels of ornithine in the blood.Spin–lattice relaxation in the rotating frame: Spin–lattice relaxation in the rotating frame is the mechanism by which Mxy, the transverse component of the magnetization vector, exponentially decays towards its equilibrium value of zero, under the influence of a radio frequency (RF) field in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). It is characterized by the spin–lattice relaxation time constant in the rotating frame, T1ρ.Neurodegeneration with brain iron accumulation: Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurological disorders in which iron accumulates in the basal ganglia, resulting in progressive dystonia, Parkinsonism, spasticity, optic atrophy or retinal degeneration and neuropsychiatric abnormalities.Hereditary Disease Foundation: The Hereditary Disease Foundation (HDF) aims to cure genetic disorders by supporting basic biomedical research.Heptadecanoic acidPhenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.Atomic mass: right |thumb|200px|Stylized [[lithium-7 atom: 3 protons, 4 neutrons, & 3 electrons (total electrons are ~1/4300th of the mass of the nucleus). It has a mass of 7.Pedigree chart: A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next,pedigree chart Genealogy Glossary -, a part of The New York Times Company.Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingSymmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Biotransformation: Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation.Gas chromatography–mass spectrometry: right|300 px|Example of a GC-MS instrument|thumbDermal fibroblast: Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers.Gunther diseaseGlucose-methanol-choline oxidoreductase family: In molecular biology, the glucose-methanol-choline oxidoreductase family (GMC oxidoreductase) is a family of enzymes with oxidoreductase activity.Tandem mass spectrometry: 300 px|right|thumb|A [[Quadrupole mass analyzer|quadrupole time-of-flight hybrid tandem mass spectrometer.]]OrnithineAmmonia transporterMicrosome: In cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.American Society of Phlebotomy Technicians: American Society of Phlebotomy Technicians (ASPT) is the second oldest certifying agency for Phlebotomy. The ASPT was founded in 1983.GetWellNetworkTable of standard reduction potentials for half-reactions important in biochemistry: The values below are standard reduction potentials for half-reactions measured at 25°C, 1 atmosphere and a pH of 7 in aqueous solution.Vacutainer: A Vacutainer blood collection tube is a sterile glass or plastic tube with a closure that is evacuated to create a vacuum inside the tube facilitating the draw of a predetermined volume of liquid. Most commonly used to collect blood samples in venipuncture, they are also used as urine collection tubes and as serum separator tubes.Generalizability theory: Generalizability theory, or G Theory, is a statistical framework for conceptualizing, investigating, and designing reliable observations. It is used to determine the reliability (i.Low-protein diet: A low-protein diet is a diet in which people reduce their intake of protein. A low-protein diet is prescribed for those with inherited metabolic disorders, such as Phenylketonuria and Homocystinuria and reduced protein levels have been used by people with kidney or liver disease.CholesterolUrea reduction ratio: For the Scottish river see: Urr WaterCousin couple: A cousin couple is a pair of cousins who are involved in a romantic or sexual relationship.

(1/628) Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis.

Cytosolic and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthases were first recognized as different chemical entities in 1975, when they were purified and characterized by Lane's group. Since then, the two enzymes have been studied extensively, one as a control site of the cholesterol biosynthetic pathway and the other as an important control site of ketogenesis. This review describes some key developments over the last 25 years that have led to our current understanding of the physiology of mitochondrial HMG-CoA synthase in the HMG-CoA pathway and in ketogenesis in the liver and small intestine of suckling animals. The enzyme is regulated by two systems: succinylation and desuccinylation in the short term, and transcriptional regulation in the long term. Both control mechanisms are influenced by nutritional and hormonal factors, which explains the incidence of ketogenesis in diabetes and starvation, during intense lipolysis, and in the foetal-neonatal and suckling-weaning transitions. The DNA-binding properties of the peroxisome-proliferator-activated receptor and other transcription factors on the nuclear-receptor-responsive element of the mitochondrial HMG-CoA synthase promoter have revealed how ketogenesis can be regulated by fatty acids. Finally, the expression of mitochondrial HMG-CoA synthase in the gonads and the correction of auxotrophy for mevalonate in cells deficient in cytosolic HMG-CoA synthase suggest that the mitochondrial enzyme may play a role in cholesterogenesis in gonadal and other tissues.  (+info)

(2/628) Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study.

BACKGROUND: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. METHODS: We used 1H NMR spectroscopy to study serum and urine from the patient. RESULTS: The concentration of N, N-dimethylglycine (DMG) was increased approximately 100-fold in the serum and approximately 20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography-mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. CONCLUSIONS: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.  (+info)

(3/628) 1H-NMR spectroscopy of body fluids: inborn errors of purine and pyrimidine metabolism.

BACKGROUND: The diagnosis of inborn errors of purine and pyrimidine metabolism is often difficult. We examined the potential of 1H-NMR as a tool in evaluation of patients with these disorders. METHODS: We performed 1H-NMR spectroscopy on 500 and 600 MHz instruments with a standardized sample volume of 500 microL. We studied body fluids from 25 patients with nine inborn errors of purine and pyrimidine metabolism. RESULTS: Characteristic abnormalities could be demonstrated in the 1H-NMR spectra of urine samples of all patients with diseases in the pyrimidine metabolism. In most urine samples from patients with defects in the purine metabolism, the 1H-NMR spectrum pointed to the specific diagnosis in a straightforward manner. The only exception was a urine from a case of adenine phosphoribosyl transferase deficiency in which the accumulating metabolite, 2,8-dihydroxyadenine, was not seen under the operating conditions used. Similarly, uric acid was not measured. We provide the 1H-NMR spectral characteristics of many intermediates in purine and pyrimidine metabolism that may be relevant for future studies in this field. CONCLUSION: The overview of metabolism that is provided by 1H-NMR spectroscopy makes the technique a valuable screening tool in the detection of inborn errors of purine and pyrimidine metabolism.  (+info)

(4/628) Inborn errors of metabolism: medical and administrative "orphans".

CONTEXT: Inborn errors of metabolism are genetic conditions that affect the normal biochemical functions of the body in any organ and at any age. More than 500 metabolic diseases are known; almost all are classified as orphan diseases under the US Food and Drug Administration guidelines (incidence < 200,000 persons) and each has its own requirements for diagnosis and treatment. Management of these complex, lifelong, multisystem disorders often requires a coordinated, multidisciplinary approach involving several subspecialists and which may include complex laboratory evaluations, genetic counseling, nutritional therapy, and unusual therapeutic approaches that have been used in only a small number of cases. RESULTS: Not infrequently, inborn errors of metabolism fall outside current standard diagnostic and treatment guidelines of managed care plans. This results in delays in diagnosis and appropriate management, with increased costs to patients and to society. CONCLUSIONS: Patients with inborn errors of metabolism should not be discriminated against and all health plans should specify that access to specialists and metabolic centers are a covered benefit of the plan. The acceptance of treatment guidelines, the development of international disease classification codes for the disorders, and the performance of cost-benefit analyses would all greatly facilitate this process. However, without recognition that these disorders require such services, and steps to provide them by the insurance industry, the care of children with metabolic disorders and other chronic diseases will continue to be a source of frustration and anger among the caregivers and the families they serve.  (+info)

(5/628) Pancreatic cancer and fibrinogen storage disease.

BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. METHODS: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. Immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.  (+info)

(6/628) An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets.

Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. Bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised.  (+info)

(7/628) Dialysis in neonates with inborn errors of metabolism.

BACKGROUND: Certain inborn errors of metabolism become manifest during the neonatal period by acute accumulation of neurotoxic metabolites leading to coma and death or irreversible neurological damage. Outcome critically depends on the immediate elimination of the accumulated neurotoxins. Recent technological progress provides improved tools to optimize the efficacy of neonatal dialysis. METHODS: We report our experience with continuous venovenous haemodialysis (CVVHD) in six neonates with hyperammonaemic coma due to urea-cycle disorders or propionic acidaemia and in one child with leucine accumulation due to maple-syrup urine disease (MSUD), in comparison with five patients managed by peritoneal dialysis (PD) (2 hyperammonaemia, 3 MSUD). Application of a new extracorporeal device specifically designed for use in small children permitted the establishment of stable blood circuits utilizing small-sized catheters, and the tight control of balanced dialysate flows over wide flow ranges. RESULTS: Plasma ammonia or leucine levels were reduced by 50% within 7.1 +/- 4.1 h by CVVHD and within 17.9 +/- 12.4 h by PD (P<0.05). Also, total dialysis time was shorter with CVVHD (25 +/- 21 h) than with PD (73 +/- 35 h, P<0.02). A comparison of the CVVHD results with published literature confirmed superior metabolite removal compared to PD, and suggested comparable efficacy as achieved with continuous haemofiltration techniques. Apart from accidental pericardial tamponade during catheter insertion in one case, no major complications were noted with CVVHD. In three of the five PD patients, dialysis was compromised by mechanical complications. None of the MSUD patients but four children with urea-cycle disorders died, two during the acute period and two later during the first year of life, with signs of severe mental delay. Of the eight children presenting with hyperammonaemic coma, the four with the most rapid dialytic ammonia removal rate (50% reduction in < 7 h) survived with no or moderate mental retardation, whereas slower toxin removal was always associated with a lethal outcome. Simulation studies showed that the efficacy of neonatal CVVHD is limited mainly by blood-flow restrictions. CONCLUSIONS: While CVVHD is the potentially most efficacious dialytic technique for treating acute metabolic crises in neonates, utmost care must be taken to provide an adequately sized vascular access.  (+info)

(8/628) Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme.

Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free N-acetylneuraminic acid (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac). We report the cloning and characterization of human UDP-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with sialuria. Their heterozygote mutations, R266W, R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266. The heterozygous nature of the mutant allele in all three patients reveals a dominant mechanism of inheritance for sialuria.  (+info)


  • See 'Inborn errors of metabolism: Metabolic emergencies' and 'Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features' and 'Inborn errors of metabolism: Identifying the specific disorder' . (
  • See 'Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features' and 'Inborn errors of metabolism: Metabolic emergencies' . (
  • Screening for inborn errors of metabolism among newborns with metabolic disturbance and/or neurological manifestations without determined cause. (
  • The selection of 9% of the studied cases for outpatient follow-up confirms that Inborn Errors of Metabolism must be suspected whenever a patient presents metabolic disturbances or neurological manifestations without a determined cause. (


  • Inborn errors of metabolism are genetic disorders that hamper the body s metabolism resulting in severe clinical manifestations. (


  • The traditional classification system for IEM groups the disorders according to the general type of metabolism involved. (
  • Disorders of purine and pyrimidine metabolism. (


  • The major classes of inborn errors of metabolism (IEM) and their characteristic clinical and biochemical features are described below. (