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Biotinidase Deficiency a
Author(s) -
WOLF BARRY,
HEARD GREGORY S.,
McVOY JULIE R. SECOR,
CRIER ROBERT E.
Publication year - 1985
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1985.tb18443.x
Subject(s) - commonwealth , west virginia , medicine , gerontology , library science , history , archaeology , computer science
There are two major types of multiple carboxylasedeficiency (MCD), the neonatal form in which the usual presenting symptoms are vomiting, lethargy and hypotonia, and the late-onset or juvenile form which can have similar symptoms to those of the neonatal disorder, but may also be characterized by skin rash, alopecia, seizures, ataxia and occasionally by developmental delay.'.' However, there have been children with the clinical features of the neonatal disorder who have presented at several months of age and vice ~ e r s a . ~ . ~ Patients with either disorder may exhibit ketolactic acidosis and organic acidemia caused by deficient activities of the biotin-dependent enzymes, propionyl-CoA carboxylase, pyruvate carbox:ylase and 0-methylcrotonyl-CoA carboxylase.'*2 The activities of carboxylases in leukocytes are usually deficient prior to the administration of pharmacologic doses of biotin but become normal or nearly normal after treatment. Differences between the carboxylase activities in extracts of fibroblasts cultured in biotin-depleted medium may be used to distinguish the disorders. Fibroblasts of children with the neonatal form exhibit deficient activities whereas fibroblasts from individuals with the late-onset form have normal activity. Serum biotin concentrations are sometimes helpful in the differential diagnosis. Patients with the late-onset form may have low serum concentrations of biotin, whereas the serum biotin concentrations are normal in the neonatal variant. The neonatal disorder has been shown to result from a deficiency in the activity of biotin holocarboxylase synthetase, the enzyme that links biotin covalently to the various apocarboxylases to form active In the late-onset form of the disorder holocarboxylase synthetase activity is normal,' and several studies have suggested that the defect is due to abnormalities in either intestinal absorption or renal excretion of the vitamin.*-" We have now demonstrated that some of these patients and several other children with late-onset MCD are deficient in biotinidase activity.