Systemic primary carnitine deficiency (SPCD) is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. (wikipedia.org)
Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine. (wikipedia.org)
Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency. (wikipedia.org)
Proper follow-up of newborn screening results for low free carnitine includes studies of the mother to determine whether her carnitine deficiency is due to SPCD or secondary to a metabolic disease or diet. (wikipedia.org)
Carnitine deficiency is a metabolic state in which carnitine concentrations in plasma and tissues are less than the levels required for normal function of the organism. (medscape.com)
Carnitine deficiency may be primary or secondary. (medscape.com)
[ 1 ] Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. (medscape.com)
Muscle carnitine deficiency (restricted to muscle) is characterized by depletion of carnitine levels in muscle with normal serum concentrations. (medscape.com)
In secondary carnitine deficiency, which is caused by other metabolic disorders (eg, fatty acid oxidation disorders, organic acidemias), carnitine depletion may be secondary to the formation of acylcarnitine adducts and the inhibition of carnitine transport in renal cells by acylcarnitines. (medscape.com)
Preterm newborns also may be at risk for developing carnitine deficiency because immature renal tubular function combined with impaired carnitine biosynthesis renders them strictly dependent on exogenous supplies to maintain normal plasma carnitine levels. (medscape.com)
Valproic acid may cause an acquired type of secondary carnitine deficiency by directly impairing renal tubular reabsorption of carnitine. (medscape.com)
In a Japanese study, primary systemic carnitine deficiency was estimated to occur in 1 per 40,000 births. (medscape.com)
In order to abate the mortality and morbidity of undiagnosed primary carnitine deficiency, this condition has been included in the expanded newborn screening program in several states within the United States. (medscape.com)
Carefully review diet compliance in secondary carnitine deficiency, considering avoidance of fasting, intake of fat-restricted, high-carbohydrate diet, and other dietary supplements that may be needed, such as riboflavin or glycine. (medscape.com)
Admit patients with carnitine deficiency for medical management of acute metabolic decompensation. (medscape.com)
Provide intravenous (IV) carnitine if the patient is known to have carnitine deficiency and a defect affecting the oxidation of long chain fatty acids has been excluded. (medscape.com)
Medications include carnitine for primary and secondary carnitine deficiency, as well as other cofactors that may be needed for different conditions associated with secondary carnitine deficiency (eg, riboflavin, coenzyme Q, biotin, hydroxocobalamin, betaine, glycine). (medscape.com)
Avoid exercise and dehydration with warm temperatures because attacks of rhabdomyolysis may occur with certain conditions that cause secondary carnitine deficiency. (medscape.com)
Prognosis of secondary carnitine deficiency depends on the nature of the disorder. (medscape.com)
Translocase deficiency and the infantile form of carnitine palmitoyltransferase II (CPT-II) deficiency have very poor prognosis regardless of treatment. (medscape.com)
Other metabolic disorders that cause secondary carnitine deficiency, such as organic acidemias, require lifelong diet modification and nutritional supplements. (medscape.com)
Family members should receive education once the work-up initiated after newborn screening results suggests primary carnitine deficiency in the newborn or in the mother. (medscape.com)
Functional genomics of OCTN2 variants informs protein-specific variant effect predictor for Carnitine Transporter Deficiency. (ucsfbenioffchildrens.org)
Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. (medscape.com)
Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. (medscape.com)
Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of beta-oxidation. (medscape.com)
On the other hand, rhabdomyolysis triggered by fasting, fever, or physical activity usually occurs in patients with disorders affecting intramitochondrial fatty acid transport and β-oxidation, such as carnitine palmitoyltransferase II deficiency (CPT2), mitochondrial trifunctional protein deficiency and very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD). (ac.ir)
Long-term follow-up of bezafibrate treatment in patients with the myopathic form of carnitine palmitoyltransferase 2 deficiency. (ac.ir)
SLC22A54
The specific transporter involved with SPCD is OCTN2, coded for by the SLC22A5 gene located on chromosome 5. (wikipedia.org)
The gene responsible for the OCTN2 carnitine transporter is SLC22A5, located at 5q31.1-32. (wikipedia.org)
SLC22A5 mutations can affect carnitine transport by impairing maturation of transporters to the plasma membrane. (medscape.com)
Tamai I. Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21). (medscape.com)
Offered carnitine supplementation1
Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well. (wikipedia.org)
Palmitoyltransferase1
With cefepime exposure, all treatment groups maintained the same levels of ATP, carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA, and lower levels of heart L-carnitine. (interesjournals.org)
Defect3
Evidence indicates that the causal factor is a defect in the muscle carnitine transporter. (medscape.com)
Wilcken B, Wiley V, Sim KG, Carpenter K. Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry. (medscape.com)
Vijay S, Patterson A, Olpin S, Henderson MJ, Clark S, Day C. Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants. (medscape.com)
Supplementation5
Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life. (wikipedia.org)
Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life. (wikipedia.org)
Hypoglycemia or sudden deaths from arrhythmias (even without cardiomyopathy) have been reported in patients who stop their carnitine supplementation against medical advice. (medscape.com)
Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates. (medscape.com)
Tandem mass spectro2
Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry. (wikipedia.org)
High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and next-generation sequencing (NGS) were used to detect the concentrations of carnitine in the blood spots and for diagnosis. (bvsalud.org)
Reabsorption1
The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption. (wikipedia.org)
Biochemical1
The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels. (wikipedia.org)
Mutations1
Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. (medscape.com)
Secondary2
Carefully monitor adequate carnitine dose in primary and secondary carnitine deficiencies by evaluating plasma carnitine levels during follow-up visits. (medscape.com)
De Vivo D, Tein I. Primary and secondary disorders of carnitine metabolism. (medscape.com)
MRNA1
The time and duration of exposure to cefepime affected the qualitative and quantitative changes in hepatic -butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA. (interesjournals.org)
Long chain1
Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA. (wikipedia.org)
Cardiomyopathy1
When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. (wikipedia.org)
Uptake1
When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts. (wikipedia.org)
Normal serum1
However, rats with normal serum L-carnitine levels showed changes in other high energy phosphate substrates and decreased phosphocreatine/ATP ratios. (interesjournals.org)
Tissue2
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Organic Cation/Ergothioneine Transporter (OCTN1) in Tissue homogenates, cell lysates and other biological fluids. (therabio.org)
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Organic Cation/Ergothioneine Transporter (OCTN1) in samples from Tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (therabio.org)
Acylcarnitines1
Acylcarnitines are formed in the mitochondria by esterification between carnitine and acyl-CoAs. (bvsalud.org)
Plasma4
SPCD leads to increased carnitine excretion in the urine and low levels in plasma. (wikipedia.org)
Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand. (wikipedia.org)
The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. (wikipedia.org)
Description: A sandwich ELISA kit for detection of Organic Cation/Ergothioneine Transporter from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (therabio.org)
Carnitine is an important amino acid for fatty acid metabolism. (wikipedia.org)
Amino acid1
Carnitine is a naturally occurring hydrophilic amino acid derivative, produced endogenously in the kidneys and liver and derived from meat and dairy products in the diet. (medscape.com)
Levels2
Biologic effects of low carnitine levels may not be clinically significant until they reach less than 10-20% of normal. (medscape.com)
In the postnatal day 1-4, 1-8, and 8-11 groups, cefepime caused severe degenerative changes in the ventricular myocardium and significantly reduced serum and heart L-carnitine levels. (interesjournals.org)
Treatment1
Lifelong treatment with L-carnitine and avoidance of fasting are required. (medscape.com)
Important1
Additionally, the ontogeny of a number of important L-carnitine homeostasis pathways was altered by cefepime. (interesjournals.org)
Carnitine binds acyl residues and helps in their elimination, decreasing the number of acyl residues conjugated with coenzyme A (CoA) and increasing the ratio between free and acylated CoA. (medscape.com)
Cell1
Exogenous LCACs, especially palmitoyl-carnitine and stearoyl-carnitine, inhibited iNKT cell expansion and promoted senescence. (bvsalud.org)