Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects.
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Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. / Santer, René; Muhle, H; Suormala, T; Baumgartner, E R; Duran, M; Yang, X; Aoki, Y; Suzuki, Y; Stephani, U.
In: MOL GENET METAB, Vol. 79, No. 3, 3, 2003, p. 160-166.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects.
AU - Santer, René
AU - Muhle, H
AU - Suormala, T
AU - Baumgartner, E R
AU - Duran, M
AU - Yang, X
AU - Aoki, Y
AU - Suzuki, Y
AU - Stephani, U
PY - 2003
Y1 - 2003
N2 - We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.
AB - We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.
M3 - SCORING: Zeitschriftenaufsatz
VL - 79
SP - 160
EP - 166
JO - MOL GENET METAB
JF - MOL GENET METAB
SN - 1096-7192
IS - 3
M1 - 3
ER -
