Adrenoleukodystrophy: An X-linked recessive disorder characterized by the accumulation of saturated very long chain fatty acids in the LYSOSOMES of ADRENAL CORTEX and the white matter of CENTRAL NERVOUS SYSTEM. This disease occurs almost exclusively in the males. Clinical features include the childhood onset of ATAXIA; NEUROBEHAVIORAL MANIFESTATIONS; HYPERPIGMENTATION; ADRENAL INSUFFICIENCY; SEIZURES; MUSCLE SPASTICITY; and DEMENTIA. The slowly progressive adult form is called adrenomyeloneuropathy. The defective gene ABCD1 is located at Xq28, and encodes the adrenoleukodystrophy protein (ATP-BINDING CASSETTE TRANSPORTERS).Diffuse Cerebral Sclerosis of Schilder: A rare central nervous system demyelinating condition affecting children and young adults. Pathologic findings include a large, sharply defined, asymmetric focus of myelin destruction that may involve an entire lobe or cerebral hemisphere. The clinical course tends to be progressive and includes dementia, cortical blindness, cortical deafness, spastic hemiplegia, and pseudobulbar palsy. Concentric sclerosis of Balo is differentiated from diffuse cerebral sclerosis of Schilder by the pathologic finding of alternating bands of destruction and preservation of myelin in concentric rings. Alpers' Syndrome refers to a heterogeneous group of diseases that feature progressive cerebral deterioration and liver disease. (From Adams et al., Principles of Neurology, 6th ed, p914; Dev Neurosci 1991;13(4-5):267-73)Erucic Acids: cis-13-Docosenoic Acids. 22-Carbon monounsaturated, monocarboxylic acids.Peroxisomal Disorders: A heterogeneous group of inherited metabolic disorders marked by absent or dysfunctional PEROXISOMES. Peroxisomal enzymatic abnormalities may be single or multiple. Biosynthetic peroxisomal pathways are compromised, including the ability to synthesize ether lipids and to oxidize long-chain fatty acid precursors. Diseases in this category include ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; rhizomelic chondrodysplasia (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC); hyperpipecolic acidemia; neonatal adrenoleukodystrophy; and ADRENOLEUKODYSTROPHY (X-linked). Neurologic dysfunction is a prominent feature of most peroxisomal disorders.Zellweger Syndrome: An autosomal recessive disorder due to defects in PEROXISOME biogenesis which involves more than 13 genes encoding peroxin proteins of the peroxisomal membrane and matrix. Zellweger syndrome is typically seen in the neonatal period with features such as dysmorphic skull; MUSCLE HYPOTONIA; SENSORINEURAL HEARING LOSS; visual compromise; SEIZURES; progressive degeneration of the KIDNEYS and the LIVER. Zellweger-like syndrome refers to phenotypes resembling the neonatal Zellweger syndrome but seen in children or adults with apparently intact peroxisome biogenesis.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Microbodies: Electron-dense cytoplasmic particles bounded by a single membrane, such as PEROXISOMES; GLYOXYSOMES; and glycosomes.Peroxisomes: Microbodies which occur in animal and plant cells and in certain fungi and protozoa. They contain peroxidase, catalase, and allied enzymes. (From Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2nd ed)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)X Chromosome: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester.Sex Chromosome Aberrations: Abnormal number or structure of the SEX CHROMOSOMES. Some sex chromosome aberrations are associated with SEX CHROMOSOME DISORDERS and SEX CHROMOSOME DISORDERS OF SEX DEVELOPMENT.Addison Disease: An adrenal disease characterized by the progressive destruction of the ADRENAL CORTEX, resulting in insufficient production of ALDOSTERONE and HYDROCORTISONE. Clinical symptoms include ANOREXIA; NAUSEA; WEIGHT LOSS; MUSCLE WEAKNESS; and HYPERPIGMENTATION of the SKIN due to increase in circulating levels of ACTH precursor hormone which stimulates MELANOCYTES.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.Refsum Disease: An autosomal recessive familial disorder that usually presents in childhood with POLYNEUROPATHY; SENSORINEURAL HEARING LOSS; ICHTHYOSIS; ATAXIA; RETINITIS PIGMENTOSA; and CARDIOMYOPATHIES. (From Joynt, Clinical Neurology, 1991, Ch37, p58-9; Rev Med Interne 1996;17(5):391-8) This condition can be caused by mutation in the genes encoding peroxisomal phytanoyl-CoA hydroxylase or proteins associated peroxisomal membrane, leading to impaired catabolism of PHYTANIC ACID in PEROXISOMES.Coenzyme A Ligases: Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1.Chondrodysplasia Punctata: A heterogeneous group of bone dysplasias, the common character of which is stippling of the epiphyses in infancy. The group includes a severe autosomal recessive form (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC), an autosomal dominant form (Conradi-Hunermann syndrome), and a milder X-linked form. Metabolic defects associated with impaired peroxisomes are present only in the rhizomelic form.Lipid Metabolism, Inborn Errors: Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Color Vision Defects: Defects of color vision are mainly hereditary traits but can be secondary to acquired or developmental abnormalities in the CONES (RETINA). Severity of hereditary defects of color vision depends on the degree of mutation of the ROD OPSINS genes (on X CHROMOSOME and CHROMOSOME 3) that code the photopigments for red, green and blue.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Acyl-CoA Oxidase: An enzyme that catalyzes the first and rate-determining steps of peroxisomal beta-oxidation of fatty acids. It acts on COENZYME A derivatives of fatty acids with chain lengths from 8 to 18, using FLAVIN-ADENINE DINUCLEOTIDE as a cofactor.Chemokine CCL22: A CC-type chemokine with specificity for CCR4 RECEPTORS. It has activity towards TH2 CELLS and TC2 CELLS.Spinocerebellar Degenerations: A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.Adrenal Insufficiency: Conditions in which the production of adrenal CORTICOSTEROIDS falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the ADRENAL GLANDS, the PITUITARY GLAND, or the HYPOTHALAMUS.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).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.

*  Proteína ABCD1 - Wikipedia

Feil R; Aubourg P; Mosser J; Douar AM; Le Paslier D; Philippe C; Mandel JL (1992). «Adrenoleukodystrophy: a complex chromosomal ... Kobayashi T; Yamada T; Yasutake T; Shinnoh N; Goto I; Iwaki T (1994). «Adrenoleukodystrophy gene encodes an 80 kDa membrane ... Aubourg P; Mosser J; Douar AM; Sarde CO; Lopez J; Mandel JL (1993). «Adrenoleukodystrophy gene: unexpected homology to a ... Se sugiere usar ,número-autores= (ayuda) Berger J; Molzer B; Faé I; Bernheimer H (1995). «X-linked adrenoleukodystrophy (ALD): ...

* | Expert Pearls - Adrenoleukodystrophy (ALD)

Adrenoleukodystrophy (ALD) - methyl vitamin B12 - 24043. Methyl vitamin B12 1500 mcg/d normalized circadian rhythms. Brain and ...

*  DMOZ - Health: Conditions and Diseases: Neurological Disorders: Demyelinating Diseases: Leukodystrophy: Adrenoleukodystrophy

... also known as X-linked adrenoleukodystrophy; melanodermic leukodystrophy; adrenal leukodystrophy; ALM; ALD. ... Sites dealing with adrenoleukodystrophy, also known as X-linked adrenoleukodystrophy; melanodermic leukodystrophy; adrenal ... "Health ... Adrenoleukodystrophy" search on: AOL - Ask - Bing - DuckDuckGo - Gigablast - Google - ixquick - Yahoo - Yandex - ... X-linked Adrenoleukodystrophy Mutations This database has been initiated to collect data on mutations found in the gene (ABCD1 ...

*  X-linked Adrenoleukodystrophy | West Florida Hospital

Learn more about X-linked Adrenoleukodystrophy at West Florida Hospital DefinitionCausesRisk ... Updated March 31, 2016. Accessed June 6, 2016. ... Adrenoleukodystrophy (ALD) is caused by an inherited defective gene.. In people with ALD, the body cannot properly break down ... X-linked adrenoleukodystrophy (ALD) is a rare inherited genetic disorder. There are 40 subtypes of leukodystrophy. X-linked ALD ...

*  Adrenoleukodystrophy

What Is Adrenoleukodystrophy?. Adrenoleukodystrophy (ALD) refers to several different inherited conditions that affect the ... Adrenoleukodystrophy. Adrenoleukodystrophy refers to several conditions that affect the nervous system and adrenal glands. ... Types of Adrenoleukodystrophy. There are three types of ALD:. *Childhood cerebral ALD mainly affects children who are between 3 ... Treatment of Adrenoleukodystrophy. Treatment methods depend on the type of ALD you have. Steroids can be used to treat ...

*  Effect of Glycerol Trierucate on Clinical Course of Adrenoleukodystrophy - Full Text View -

Adrenoleukodystrophy. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System ... Effect of Glycerol Trierucate on Clinical Course of Adrenoleukodystrophy. This study has suspended participant recruitment. ... Study of Glyceryl Trierucate and Glyceryl Trioleate (Lorenzo's Oil) Therapy in Male Children With Adrenoleukodystrophy. ... Genetic and Rare Diseases Information Center resources: X-linked Adrenoleukodystrophy Adrenomyeloneuropathy Sphingolipidosis ...

*  DMOZ - Health: Conditions and Diseases: Neurological Disorders: Demyelinating Diseases: Multiple Sclerosis: Research

A 501(c)3 non-profit organization focused on improving the quality of life for those living with adrenoleukodystrophy (ALD) and ...

*  Adrenoleukodystrophy unravelled

X-ALD project undertook an initiative to understand the mechanisms responsible for the pathogenesis of adrenoleukodystrophy ( ... Adrenoleukodystrophy unravelled. July 30, 2012 Credit: Thinkstock The European X-ALD project undertook an initiative to ... Using this model, the EU-funded X-linked Adrenoleukodystrophy (X-ALD): pathogenesis, animal models and therapy (X-ALD) project ... understand the mechanisms responsible for the pathogenesis of adrenoleukodystrophy (ALD). The gene therapy approach for ...

*  Adrenoleukodystrophy | Radiology Reference Article |

Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic peroxisomal disorder characterised by a lack of oxidation of very ... Adrenoleukodystrophy: new CT findings. AJNR Am J Neuroradiol. 4 (4): 951-4. AJNR Am J Neuroradiol (abstract) - Pubmed citation ... Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic peroxisomal disorder characterised by a lack of oxidation of very ... X-Linked Adrenoleukodystrophy. 1999 Mar 26 [Updated 2015 Apr 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. ...

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Lenti-D is being evaluated in a phase 2/3 clinical study for treatment of rare genetic disease cerebral adrenoleukodystrophy ( ...

*  Very Long Chain Fatty Acids

These disorders include (A) Zellweger spectrum disorders of peroxisomal biogenesis, (B) X-linked adrenoleukodystrophy (X-ALD) ... These disorders include (A) Zellweger spectrum disorders of peroxisomal biogenesis, (B) X-linked adrenoleukodystrophy (X-ALD) ...

*  Adrenoleukodystrophy Treatment News and Symptoms Information - Comfort Finders

Latest Adrenoleukodystrophy Treatment News and Research. Sunshine from Spain: Minoryx Targets Rare Genetic Diseases. Labiotech. ... What is Adrenoleukodystrophy?. (Symptoms, Causes & Treatment). According to the U.S. National Library of Medicine, ... Abstract: Adrenoleukodystrophy (ALD) is a rare, X-linked peroxisomal disorder of impaired very long-chain fatty-acid metabolism ... Mission: Minoryx Therapeutics is focused on a group of rare genetic diseases like X-Linked Adrenoleukodystrophy (X-ALD) and ...

*  Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy.

To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which ... Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy. Academic ... beneficial effects of antioxidants and enhance the rationale for translation into clinical trials for X-adrenoleukodystrophy. ...

*  Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients.

Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic ... Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients.. ... CONCLUSIONS: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high ... Abstract BACKGROUND: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is ...

*  Pseudoneonatal adrenoleukodystrophy | Genetic and Rare Diseases Information Center (GARD) - an NCATS Program

... and questions answered by our Genetic and Rare Diseases Information Specialists for Pseudoneonatal adrenoleukodystrophy ... Pseudoneonatal adrenoleukodystrophy Title Other Names:. Peroxisomal Acyl-CoA oxidase deficiency; Straight-chain Acyl-CoA ... The following diseases are related to Pseudoneonatal adrenoleukodystrophy. If you have a question about any of these diseases, ... Genetics Home Reference (GHR) contains information on Pseudoneonatal adrenoleukodystrophy. This website is maintained by the ...

*  Adrenoleukodystrophy Appointments - Mayo Clinic

Adrenoleukodystrophy - Comprehensive overview covers diagnosis and treatment of this genetic disorder that affects the brain. ... Accessed Oct. 11, 2014. ... X-linked adrenoleukodystrophy. Genetics Home Reference. ... and others evaluate and treat adults and children who have adrenoleukodystrophy at Mayo Clinic in Rochester, Minnesota. The ...

*  Adrenoleukodystrophy | Health Encyclopedia |

Adrenoleukodystrophy. Definition. Adrenoleukodystrophy describes several closely related inherited disorders that disrupt the ... Your child develops symptoms of X-linked adrenoleukodystrophy. *Your child has X-linked adrenoleukodystrophy and is getting ... X-linked Adrenoleukodystrophy; Adrenomyeloneuropathy; Childhood cerebral adrenoleukodystrophy; ALD; Schilder-Addison Complex. ... Adrenoleukodystrophy is usually passed down from parent to child as an X-linked genetic trait. It therefore affects mostly ...

*  Leukodystrophies - Adrenoleukodystrophy - Renal and Urology News

What are the possible outcomes of X-linked adrenoleukodystrophy?. Boys with X-ALD can have a normal life expectancy and pursue ... "X-linked adrenoleukodystrophy". Nat Clin Pract Neurol. vol. 3. 2007. pp. 140-51. ... Are you sure your patient has X-linked adrenoleukodystrophy? What are the typical findings for this disease?. The most common ... If you are able to confirm that the patient has X-linked adrenoleukodystrophy, what treatment should be initiated?. After the ...

*  X-linked Adrenoleukodystrophy | Medical City Dallas

Learn more about X-linked Adrenoleukodystrophy at Medical City Dallas DefinitionCausesRisk ... Updated March 31, 2016. Accessed June 6, 2016. ... Adrenoleukodystrophy (ALD) is caused by an inherited defective gene.. In people with ALD, the body cannot properly break down ... X-linked adrenoleukodystrophy (ALD) is a rare inherited genetic disorder. There are 40 subtypes of leukodystrophy. X-linked ALD ...

*  Adrenoleukodystrophy (ALD) | Programs and Services | Boston Children's Hospital

Adrenoleukodystrophy (ALD) , Programs and Services. Our team of experts provides specialized care to meet the needs of you or ...

*  Pathology Outlines - Storage diseases, Adrenoleukodystrophy

Storage diseases - Adrenoleukodystrophy. Author: Nat Pernick, M.D. (see Authors page). Revised: 15 January 2016, last major ... Due to mutations of adrenoleukodystrophy protein (ADLP) in peroxisomal membrane at Xq28, which causes defective oxidation of ... Cite this page: Storage diseases, Adrenoleukodystrophy. website. ...

*  Adrenoleukodystrophy | Radiology Case |

Features are consistent with X-linked adrenoleukodystrophy ... Adrenoleukodystrophy. Case contributed by A.Prof Frank Gaillard ...

*  X-linked adrenoleukodystrophy | Holy Cross Hospital

detailed search results - X-linked adrenoleukodystrophy

AdrenoleukodystrophyBalo concentric sclerosisCanola: Canola refers to both an edible oil (also known as canola oil) produced from the seed of any of several varieties of the Brassicaceae family of plants, and to those plants, namely a cultivar of Brassica napus L., Brassica rapa subsp.Peroxisomal biogenesis factor 11: Peroxisomal biogenesis factor 11 (PEX11) are peroxisomal membrane proteins which promote peroxisome division in eukaryotic cells.ZellwegerTransporter associated with antigen processing: Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules.Microbody: A microbody is a type of organelle that is found in the cells of plants, protozoa, and animals. Organelles in the microbody family include peroxisomes, glyoxysomes, glycosomes and hydrogenosomes.Peroxisome: 300px|right|thumb|Basic structure of a peroxisomeHeptadecanoic acidSmith–Fineman–Myers syndrome: Smith–Fineman–Myers syndrome (SFMS1), also called X-linked mental retardation-hypotonic facies syndrome 1 (MRXHF1), Carpenter–Waziri syndrome, Chudley–Lowry syndrome, SFMS, Holmes–Gang syndrome and Juberg–Marsidi syndrome (JMS), is a rare X-linked recessive congenital disorder that causes birth defects. This syndrome was named after 3 men, Richard D.TrioleinAddison's disease in canines: Addison's disease in canines refers to hypoadrenocorticism, or Addison's disease, when it occurs in canines. The first case of Addison's disease in dogs was recorded in 1953, over 100 years after it was described in humans by Thomas Addison.ACSL6: Acyl-CoA synthetase long-chain family member 6 is an enzyme that in humans is encoded by the ACSL6 gene. Long-chain acyl-CoA synthetases such as ACSL6, catalyze the formation of acyl-CoA from fatty acids, ATP, and CoA.Chondrodysplasia punctataNeutral 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.Dermal 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.Gene therapy for color blindness: Gene therapy for color blindness is an experimental gene therapy aiming to convert congenitally colorblind individuals to trichromats by introducing a photopigment gene that they lack. Though partial color blindness is considered only a mild disability and is controversial whether it is even a disorder, it is a condition that affects many people, particularly males.Genetic linkage: Genetic linkage is the tendency of alleles that are located close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Genes whose loci are nearer to each other are less likely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be genetically linked.Critical illness-related corticosteroid insufficiency: Critical illness-related corticosteroid insufficiency (CIRCI) is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.Table 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.

(1/213) Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy.

Inherited defects in the peroxisomal ATP-binding cassette (ABC) transporter adrenoleukodystrophy protein (ALDP) lead to the lethal peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), for which no efficient treatment has been established so far. Three other peroxisomal ABC transporters currently are known: adrenoleukodystrophy-related protein (ALDRP), 70 kDa peroxisomal membrane protein (PMP70) and PMP70- related protein. By using transient and stable overexpression of human cDNAs encoding ALDP and its closest relative ALDRP, we could restore the impaired peroxisomal beta-oxidation in fibroblasts of X-ALD patients. The pathognomonic accumulation of very long chain fatty acids could also be prevented by overexpression of ALDRP in immortalized X-ALD cells. Immunofluorescence analysis demonstrated that the functional replacement of ALDP by ALDRP was not due to stabilization of the mutated ALDP itself. Moreover, we were able to restore the peroxisomal beta-oxidation defect in the liver of ALDP-deficient mice by stimulation of ALDRP and PMP70 gene expression through a dietary treatment with the peroxisome proliferator fenofibrate. These results suggest that a correction of the biochemical defect in X-ALD could be possible by drug-induced overexpression or ectopic expression of ALDRP.  (+info)

(2/213) Retroviral-mediated adrenoleukodystrophy-related gene transfer corrects very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts: implications for therapy.

X-linked adrenoleukodystrophy is a demyelinating disorder of the central nervous system with an impaired very long chain fatty acid metabolism. The adrenoleukodystrophy gene encodes a peroxisomal membrane protein that is part of a family of related ATP-binding transporters including the adrenoleukodystrophy-related protein. The adrenoleukodystrophy protein and adrenoleukodystrophy-related protein show 66% identity and have a mirror expression in most mouse tissues. We show that retroviral-mediated adrenoleukodystrophy-related gene transfer corrects very long chain fatty acid accumulation in adrenoleukodystrophy fibroblasts, irrespective of the presence or absence of adrenoleukodystrophy protein. Pharmacological approaches aiming at overexpressing the adrenoleukodystrophy-related gene in the central nervous system of adrenoleukodystrophy patients might thus offer new therapeutic leads.  (+info)

(3/213) Beyond the disorder: one parent's reflection on genetic counselling.

As a mother of two sons with adrenoleukodystrophy the author of this paper writes about her experiences of genetic counselling following the diagnosis. She discusses the dilemmas, emotions and aftermath this knowledge has brought to her family and the roles she played. Personal concerns are raised about the values guiding genetic counselling which, she found, focused on the technical details without considering the ethical implications arising from the new knowledge or the emotional dilemmas of prenatal testing. Some consequences of choice and the value of hope are discussed. She concludes by challenging genetic counsellors to deliver a service which not only provides technical information but is cognisant of the ethical considerations this information may foist upon a family.  (+info)

(4/213) Preventing neurodegeneration in the Drosophila mutant bubblegum.

The Drosophila melanogaster recessive mutant bubblegum (bgm) exhibits adult neurodegeneration, with marked dilation of photoreceptor axons. The bubblegum mutant shows elevated levels of very long chain fatty acids (VLCFAs), as seen in the human disease adrenoleukodystrophy (ALD). In ALD, the excess can be lowered by dietary treatment with "Lorenzo's oil," a mixture of unsaturated fatty acids. Feeding the fly mutant one of the components, glyceryl trioleate oil, blocked the accumulation of excess VLCFAs as well as development of the pathology. Mutant flies thus provide a potential model system for studying mechanisms of neurodegenerative disease and screening drugs for treatment.  (+info)

(5/213) Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo's oil".

OBJECTIVES: X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal fatty acid oxidation, biochemically characterised by the accumulation of saturated very long chain fatty acids (VLCFAs), particularly hexacosanoic acid (C26:0). Dietary treatment with a 4:1 mixture of glyceroltrioleate and glyceroltrierucate ("Lorenzo's oil") normalises plasma VLCFA concentrations, but neither ameliorates nor arrests the rapid progression of neurological symptoms in the cerebral variants of X-ALD. The efficacy of "Lorenzo's oil" in the milder phenotypes of X-ALD was assessed, as this has been much less investigated. METHODS: Twenty two patients who were treated with "Lorenzo's oil" for at least 12 months for a median period of 2.5 (range 1.0-6.0) years were studied. Two had asymptomatic ALD, four the "Addison only" variant, 13 adrenomyeloneuropathy (AMN), and three were symptomatic female carriers. RESULTS: The plasma C26:0 concentration normalised or near normalised in 19 patients (86%), in the three others it decreased significantly. Nevertheless, disability as measured with the extended disability status scale score increased mildly (0.5 (95% confidence interval (95% CI) 0.25-1.0)) in the 16 patients with neurological symptoms. Furthermore, one "Addison only" patient and one patient with AMN developed cerebral demyelination, and another "Addison only" patient developed AMN. Adrenocortical insufficiency evolved in one patient with AMN, and hypogonadism in one patient with asymptomatic ALD and two patients with AMN. Nerve conduction, evoked potential studies (SEP, BAEP, VEP), and abnormalities on cerebral MRI did not improve. On the other hand, side effects were often noted-namely, mild increases in liver enzymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). We also found a mild decrease in haemoglobin concentration and leucocyte count. CONCLUSIONS: The data suggest that treatment with "Lorenzo's oil" neither improved neurological or endocrine function nor arrested progression of the disease. Furthermore, the oil often induced adverse effects. Therefore, it is advocated that "Lorenzo's oil" should not be prescribed routinely to patients with X-ALD who already have neurological deficits.  (+info)

(6/213) Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation.

We investigated early immunological reconstitution and the production of circulating inflammatory mediators and their relationship to aGVHD in children during the first 100 days following unrelated UCBT. Nine patients had an underlying malignant disease (ALL, ANLL), and two, non-malignant diseases (SAA, ALD). The median age was 10 years (range: 1.25-21). Seven of 11 patients were alive by day 100, two died from regimen-related toxicity, and two died from severe aGVHD (grade >/=III). Myeloid engraftment (ANC >/=500/mm3 x 2 days) occurred at a median of 24 days (range: 14-55), while platelet engraftment (platelet count >/=20 000/mm3 untransfused x 7 days) was delayed and occurred at a median of 52 days (range: 33-95). The mean cell dose of CD34+ cells was 3.3 +/- 3.51 x 10(5)/kg, and of CD34+/CD41+ cells was 3.94 +/- 3.99 x 10(4)/kg. Acute GVHD (grade II-IV) developed in seven patients (77%), and severe aGVHD (grade III-IV) developed in five patients (55%). Serum levels of IL-2Ralpha, IL-2, IL-4, IL-7, IL-12, and IFNgamma were not significantly different between patients with grades 0-I aGVHD and patients with grades II-IV aGVHD. Evaluation of immunological reconstitution on day 90 post UCBT demonstrated an early recovery of the absolute numbers of B cells (CD19+) and NK cells (CD3-/CD56+). Immunoglobulin levels for IgG, IgM and IgA remained normal throughout the study period. PMN functional studies demonstrated normal superoxide generation, bacterial killing (BK), and chemotaxis (CTX). However, both helper (CD3+/CD4+) and suppressor (CD3+/CD8+) T cell subsets remained low during the first 100 days post UCBT with mean +/- s.e.m. values of 120 +/- 29/mm3 and 10 +/- 50/mm3, respectively (normal = 900-2860/mm3 (CD3/CD4), normal = 630-1910/mm3 (CD3/CD8)). Mitogen response studies showed low blastogenesis to PHA and PWM, with a mean c.p.m. +/- s.e.m. value of 1.7 +/- 0.67 x 10(4) for PHA (NL >/= 75 x 10(3)) and 8.42 +/- 4.1 x 10(3) for PWM (NL >/=25 x 10(3)). In conclusion, serum levels of inflammatory mediators were not predictive nor did they correlate with the severity of aGVHD. Recovery of NK cells, B cells, and PMN functions occurred within the first 90 days post transplant. However, T cell subsets, CD3+/CD4+ and CD3+/CD8+, and T cell functional activity remained significantly decreased and may account for the high incidence of infectious morbidity seen during this immediate post UCBT period.  (+info)

(7/213) Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters.

Mammalian peroxisomal proteins adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related protein (ALDRP), and 70-kDa peroxisomal protein (PMP70) belong to the superfamily of ATP-binding cassette (ABC) transporters. Unlike many ABC transporters that are single functional proteins with two related halves, ALDP, ALDRP, and PMP70 have the structure of ABC half-transporters. The dysfunction of ALDP is responsible for X-linked adrenoleukodystrophy (X-ALD), a neurodegenerative disorder in which saturated very long-chain fatty acids accumulate because of their impaired peroxisomal beta-oxidation. No disease has so far been associated with mutations of adrenoleukodystrophy-related or PMP70 genes. It has been proposed that peroxisomal ABC transporters need to dimerize to exert import functions. Using the yeast two-hybrid system, we show that homo- as well as heterodimerization occur between the carboxyl-terminal halves of ALDP, ALDRP, and PMP70. Two X-ALD disease mutations located in the carboxyl-terminal half of ALDP affect both homo- and heterodimerization of ALDP. Co-immunoprecipitation demonstrated the homodimerization of ALDP, the heterodimerization of ALDP with PMP70 or ALDRP, and the heterodimerization of ALDRP with PMP70. These results provide the first evidence of both homo- and heterodimerization of mammalian ABC half-transporters and suggest that the loss of ALDP dimerization plays a role in X-ALD pathogenesis.  (+info)

(8/213) X-linked adrenoleukodystrophy: the role of contrast-enhanced MR imaging in predicting disease progression.

BACKGROUND AND PURPOSE: Early assignment of disease progression among patients with X-linked adrenoleukodystrophy (ALD) is critical for the appropriate selection of effective therapy. We evaluated the association between contrast enhancement on T1-weighted spin-echo MR images and disease progression. METHODS: Clinical charts of patients with X-linked ALD were reviewed for age, availability of MR images of the brain, severity of neurologic impairment, and duration and number of follow-up evaluations. Forty-three male patients with X-linked ALD had undergone multiple MR imaging examinations of the brain that consisted of at least sagittal and axial T1-weighted spin-echo, axial double-echo spin-echo, and contrast-enhanced axial T1-weighted spin-echo imaging. The MR images were reviewed for the presence of contrast enhancement. In addition, global disease burden, as shown by the double-echo spin-echo images, was assessed using a visual scoring method (Loes score). RESULTS: Enhancement was seen on the initial T1-weighted spin-echo MR images of 21 (49%) patients; 18 (86%) of the 21 patients had disease progression revealed by the follow-up evaluations based on MR imaging (Loes) and neurologic scores. No enhancement was seen on the initial T1-weighted spin-echo MR images of 22 (51%) patients; for 18 (82%) of the 22 patients, no evidence of disease progression was revealed by the follow-up evaluations. CONCLUSION: There is a very strong association between the presence of contrast enhancement on T1-weighted MR images and X-linked ALD progression based on clinical evaluation and MR imaging.  (+info)


  • Abstract BACKGROUND: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. (


  • The European X-ALD project undertook an initiative to understand the mechanisms responsible for the pathogenesis of adrenoleukodystrophy (ALD). (
  • Using this model, the EU-funded X-linked Adrenoleukodystrophy (X-ALD): pathogenesis, animal models and therapy (X-ALD) project aimed to prove the role of ALD protein in VLCFA transport. (
  • Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. (

long chain

  • The adrenoleukodystrophy protein (ALDP) helps your body break down very long chain fatty acids (VLCFA). (
  • Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic peroxisomal disorder characterised by a lack of oxidation of very long chain fatty acids (VLCFAs) that results in severe inflammatory demyelination of the periventricular deep white matter with posterior-predominant pattern and early involvement of the splenium of the corpus callosum and parietal white matter changes. (


  • The other peroxisomal disorders should also be discarded, especially neonatal adrenoleukodystrophy (see this term), which presents similar clinical manifestations. (


  • Adrenoleukodystrophy refers to several conditions that affect the nervous system and adrenal glands. (


  • The most common symptoms in X-linked adrenoleukodystrophy (X-ALD) are both neurologic and endocrine in nature. (


  • Genetic counseling is recommended for prospective parents with a family history of X-linked adrenoleukodystrophy. (
  • X-linked adrenoleukodystrophy (ALD) is a rare inherited genetic disorder. (


  • CONCLUSIONS: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1H magnetic resonance spectroscopy in individual patients without the need for sedation. (



  • Abnormal MRI findings precede clinical findings in all forms of adrenoleukodystrophy 13 . (
  • Adrenoleukodystrophy: new CT findings. (


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  • OBJECTIVES: I. Evaluate the clinical efficacy of combination glyceryl trierucate and glyceryl trioleate (Lorenzo's Oil) therapy in boys with X-linked adrenoleukodystrophy. (



  • A specific treatment for X-linked adrenoleukodystrophy is not available, but bone marrow transplantation can be performed and can cure patients of the condition. (
  • Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients. (



  • Our ultimate goal is to develop new therapies for X-linked adrenoleukodystrophy (X-ALD), the most frequent inherited monogenie demyelinating disease of the central nervous system (1:18,000). (


  • (