Skip to main content
PMC home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 1992 Jan;67(1):115–119. doi: 10.1136/adc.67.1.115

A biotinidase Km variant causing late onset bilateral optic neuropathy.

V T Ramaekers 1, T M Suormala 1, M Brab 1, R Duran 1, G Heimann 1, E R Baumgartner 1
PMCID: PMC1793569  PMID: 1739323

Abstract

A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a mutant biotinidase with residual activity of 4.4% assayed routinely. Biocytin excretion in urine was only slightly increased. Further investigations on plasma biotinidase revealed biphasic kinetics with two different reduced values for maximum reaction velocity (Vmax) and two for the Michaelis constant (Km), one being almost normal and the other considerably raised. In contrast to this patient, two age matched children with partial biotinidase deficiency (2.8% and 2.9% of normal), but with a normal Km for biocytin, remained asymptomatic. After six months of oral substitution with 10 mg biotin per day the coecocentral and peripheral scotomata regressed, the pyramidal signs in the lower limbs disappeared, and further progression of the motor neuropathy arrested. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease, should include biotinidase deficiency.

Full text

PDF
115

Images in this article

116Figure 1
on p.116

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baumgartner E. R., Suormala T. M., Wick H., Probst A., Blauenstein U., Bachmann C., Vest M. Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. Pediatr Res. 1989 Sep;26(3):260–266. doi: 10.1203/00006450-198909000-00021. [DOI] [PubMed] [Google Scholar]
  2. Frigg M., Brubacher G. Biotin deficiency in chicks fed a wheat-based diet. Int J Vitam Nutr Res. 1976;46(3):314–321. [PubMed] [Google Scholar]
  3. KNAPPE J., BRUEMMER W., BIEDERBICK K. REINIGUNG UND EIGENSCHAFTEN DER BIOTINIDASE AUS SCHWEINENIEREN UND LACTOBACILLUS CASEI. Biochem Z. 1963;338:599–613. [PubMed] [Google Scholar]
  4. McVoy J. R., Levy H. L., Lawler M., Schmidt M. A., Ebers D. D., Hart P. S., Pettit D. D., Blitzer M. G., Wolf B. Partial biotinidase deficiency: clinical and biochemical features. J Pediatr. 1990 Jan;116(1):78–83. doi: 10.1016/s0022-3476(05)81649-x. [DOI] [PubMed] [Google Scholar]
  5. Singh G., Lott M. T., Wallace D. C. A mitochondrial DNA mutation as a cause of Leber's hereditary optic neuropathy. N Engl J Med. 1989 May 18;320(20):1300–1305. doi: 10.1056/NEJM198905183202002. [DOI] [PubMed] [Google Scholar]
  6. Suormala T. M., Baumgartner E. R., Bausch J., Holick W., Wick H. Quantitative determination of biocytin in urine of patients with biotinidase deficiency using high-performance liquid chromatography (HPLC). Clin Chim Acta. 1988 Oct 31;177(3):253–269. doi: 10.1016/0009-8981(88)90070-8. [DOI] [PubMed] [Google Scholar]
  7. Suormala T. M., Baumgartner E. R., Wick H., Scheibenreiter S., Schweitzer S. Comparison of patients with complete and partial biotinidase deficiency: biochemical studies. J Inherit Metab Dis. 1990;13(1):76–92. doi: 10.1007/BF01799335. [DOI] [PubMed] [Google Scholar]
  8. Suormala T., Wick H., Bonjour J. P., Baumgartner E. R. Rapid differential diagnosis of carboxylase deficiencies and evaluation for biotin-responsiveness in a single blood sample. Clin Chim Acta. 1985 Jan 30;145(2):151–162. doi: 10.1016/0009-8981(85)90282-7. [DOI] [PubMed] [Google Scholar]
  9. Sweetman L., Nyhan W. L. Inheritable biotin-treatable disorders and associated phenomena. Annu Rev Nutr. 1986;6:317–343. doi: 10.1146/annurev.nu.06.070186.001533. [DOI] [PubMed] [Google Scholar]
  10. Wastell H. J., Bartlett K., Dale G., Shein A. Biotinidase deficiency: a survey of 10 cases. Arch Dis Child. 1988 Oct;63(10):1244–1249. doi: 10.1136/adc.63.10.1244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wolf B., Grier R. E., Allen R. J., Goodman S. I., Kien C. L. Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta. 1983 Jul 15;131(3):273–281. doi: 10.1016/0009-8981(83)90096-7. [DOI] [PubMed] [Google Scholar]
  12. Wolf B., Heard G. S., Weissbecker K. A., McVoy J. R., Grier R. E., Leshner R. T. Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol. 1985 Nov;18(5):614–617. doi: 10.1002/ana.410180517. [DOI] [PubMed] [Google Scholar]
  13. Zierler K. Misuse of nonlinear Scatchard plots. Trends Biochem Sci. 1989 Aug;14(8):314–317. doi: 10.1016/0968-0004(89)90157-6. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES