Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency

E. Holme, Jun Kudo, N. Shimizu, Y. Suzuki, O. Sakamoto, X. Li, Y. Aoki, M. Hiratsuka, K. Narisawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabolism characterised by metabolic ketoacidosis and skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this disease is usually between the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the patient developed his first episode of acidosis at age 8 years and had an exceptionally slow response to biotin therapy. A homozygous mutation was identified at the +5 position of the splice donor site in intron 10 of the HCS gene (IVs10 + 5(g → a)), resulting in abnormal splicing of HCS mRNA. A moderate decrease in the amount of normal HCS mRNA may account for the atypical, late-onset phenotype of this patient. Conclusion: Molecular analysis is a useful tool for understanding the phenotypic variations in holocarboxylase synthetase deficiency.

Original languageEnglish
Pages (from-to)18-22
Number of pages5
JournalEuropean Journal of Pediatrics
Volume159
Issue number1-2
Publication statusPublished - 2000

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Holocarboxylase Synthetase Deficiency
biotin carboxylase
Biotin
Messenger RNA
RNA Splice Sites
Ketosis
Acidosis
Introns
Phenotype
Skin
Mutation
Genes
holocarboxylase synthetases

Keywords

  • Biotin
  • Holocarboxylase synthetase
  • Multiple carboxylase deficiency
  • Splice error

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Holme, E., Kudo, J., Shimizu, N., Suzuki, Y., Sakamoto, O., Li, X., ... Narisawa, K. (2000). Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. European Journal of Pediatrics, 159(1-2), 18-22.

Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. / Holme, E.; Kudo, Jun; Shimizu, N.; Suzuki, Y.; Sakamoto, O.; Li, X.; Aoki, Y.; Hiratsuka, M.; Narisawa, K.

In: European Journal of Pediatrics, Vol. 159, No. 1-2, 2000, p. 18-22.

Research output: Contribution to journalArticle

Holme, E, Kudo, J, Shimizu, N, Suzuki, Y, Sakamoto, O, Li, X, Aoki, Y, Hiratsuka, M & Narisawa, K 2000, 'Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency', European Journal of Pediatrics, vol. 159, no. 1-2, pp. 18-22.
Holme E, Kudo J, Shimizu N, Suzuki Y, Sakamoto O, Li X et al. Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. European Journal of Pediatrics. 2000;159(1-2):18-22.
Holme, E. ; Kudo, Jun ; Shimizu, N. ; Suzuki, Y. ; Sakamoto, O. ; Li, X. ; Aoki, Y. ; Hiratsuka, M. ; Narisawa, K. / Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. In: European Journal of Pediatrics. 2000 ; Vol. 159, No. 1-2. pp. 18-22.
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