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Skin fibroblast carnitine uptake in secondary carnitine deficiency disorders
Author(s) -
Tein I.,
De Vivo D. C.,
Ranucci D.,
DiMauro S.
Publication year - 1993
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf00711327
Subject(s) - carnitine , fibroblast , medicine , endocrinology , human genetics , biology , biochemistry , genetics , cell culture , gene
Summary Skin fibroblast carnitine uptake studies may identify and differentiate primary and secondary carnitine deficiency disorders. To confirm the specificity of these studies in differentiating primary from secondary carnitine deficiency disorders, we have studied carnitine uptake in the cultured skin fibroblasts from 5 children who have various enzymatic defects in intramitochondrial β‐oxidation including short‐chain, medium‐chain and long‐chain acyl‐CoA dehydrogenase and short‐chain l ‐3‐hydroxyacyl‐CoA dehydrogenase deficiencies, and in 4 children with cytochrome oxidase deficiency. Carnitine uptake was normal in the intramitochondrial β‐oxidation cases, suggesting other mechanisms for their carnitine deficiency. Therefore, intramitochondrial β‐oxidation defects associated with carnitine deficiency can be differentiated from primary carnitine deficiency not only by the presence of an abnormal dicarboxylic aciduria but by normal skin fibroblast carnitine uptake. In contrast to these findings, carnitine uptake in the cultured skin fibroblasts of four children with secondary carnitine deficiency due to cytochrome oxidase deficiency demonstrated a partial decrease in the maximal velocity of uptake (20–47% control V max ), similar to that observed in the primary carnitine deficiency heterozygotes. We propose that this observation may be due to a generalized decrease in intracellular ATP, thus decreasing the efficiency of the energy‐ and sodium‐dependent carnitine transporter. We conclude that carnitine uptake studies in cultured skin fibroblasts will contribute to an understanding of the mechanisms of carnitine depletion in the primary and secondary carnitine deficiency disorders.