Biotinidase is the enzyme that cleaves biotin from the final products of the proteolytic degradation of biotin-dependent carboxylases, thus recycling the vitamin. Biotinidase activity is deficient in most children with late-onset multiple carboxylase defeiciency. Affected individuals may exhibit neurologic and cutaneous features including seizures, hypotonia, ataxia, skin rash, alopecia and developmental delay, which may progress to come and ultimately death. All children with biotinidase deficiency who have been treated with biotin have improved clinically. Since the disorder met the major criteria for inclusion in newborn screening programs, we developed a simple test for determining biotinidase activity using the same blood-soaked filter paper samples used in most programs. We have been screening all the newborn infants born in Virginia since January 24, 1984 and have detected three newborns with the deficiency and two affected siblings of one of these infants. Based on our results more than a dozen states and ten foreign countries have started or will start similar newborn screening programs. Several of these programs have already detected newborns with the enzyme deficiency. We proposed to collaborate with designated physicians in states that are currently screening for biotinidase deficiency and physicians who have identified symptomatic individuals to obtain a deficiency and physicians who have identified symptomatic individuals to obtain a better understanding of the initial features and natural history of the disorder. Clinical and biochemical evaluations will be performed at regular intervals on infants and children with biotinidase deficiency detected by newborn screening or who have been identified after developing symptoms. Evaluation of their family members, particularly siblings, should provide insight into the variation of expression of the disorder and the possible existence of benign variants. Moreover, this work will provide information about the possible manifestations in heterozygotes for the disorder and the potential adverse effects of biotin treatment.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD023223-03S1
Application #
3323272
Study Section
Biochemistry Study Section (BIO)
Project Start
1987-08-01
Project End
1992-11-30
Budget Start
1989-08-01
Budget End
1990-11-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Salbert, B A; Pellock, J M; Wolf, B (1993) Characterization of seizures associated with biotinidase deficiency. Neurology 43:1351-5
Bousounis, D P; Camfield, P R; Wolf, B (1993) Reversal of brain atrophy with biotin treatment in biotinidase deficiency. Neuropediatrics 24:214-7
Weissbecker, K A; Wolf, B; Eaves, L J et al. (1993) Combined pedigree and twin family study to determine the sources of variation in serum biotinidase activity: the usefulness of multiple study designs. Am J Med Genet 47:231-40
Salbert, B A; Astruc, J; Wolf, B (1993) Ophthalmologic findings in biotinidase deficiency. Ophthalmologica 206:177-81
Hart, P S; Hymes, J; Wolf, B (1992) Biochemical and immunologic characterization of serum biotinidase in partial biotinidase deficiency. Pediatr Res 31:261-5
Hart, P S; Hymes, J; Wolf, B (1992) Biochemical and immunological characterization of serum biotinidase in profound biotinidase deficiency. Am J Hum Genet 50:126-36
Hart, P S; Barnstein, B O; Secor McVoy, J R et al. (1992) Comparison of profound biotinidase deficiency in children ascertained clinically and by newborn screening using a simple method of accurately determining residual biotinidase activity. Biochem Med Metab Biol 48:41-5
Wolf, B (1991) Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis 14:923-7
Wolf, B; Heard, G S (1991) Biotinidase deficiency. Adv Pediatr 38:1-21
Wolf, B; Heard, G S (1990) Screening for biotinidase deficiency in newborns: worldwide experience. Pediatrics 85:512-7

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