|| common in clinvar
|?|| (C;C) (C;G) (G;G) ||28|
|| AFFECT FUNCTION
| Disease Association
|| Defects in BTD are the cause of biotinidase deficiency (BTD deficiency) (MIM:253260); also called late onset multiple carboxylase deficiency. BTD deficiency is a disease characterized by seizures, hypotonia, skin rash, alopecia, ataxia, hearing loss, and optic atrophy. If untreated, symptoms usually become progressively worse, and coma and death may occur. Profound BTD deficiency has a 10% or less mean normal serum activity. Partial BTD deficiency has a 10%-30% of mean normal serum activity. Children with partial BTD deficiency and who are not treated with biotin do not usually exhibit symptoms unless they are stressed (prolonged infection...). Partial BTD deficiency usually occurs when an individual has one allele that results in nearly total loss of activity in combination with an allele having the ""D424H"" mutation.
[PMID 9375914] Profound biotinidase deficiency in two asymptomatic adults.
[PMID 9654207] Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.
[PMID 10400129] Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.
|| Low clinical importance, pathogenic
|| This variant is implicated in partial and profound biotinidase deficiency. Alone, this variant is estimated to have a 52% loss of enzymatic activity. This variant is often found with A171T, and together they are reported to cause profound deficiency. Notably there is a report of asymptomatic double-mutant adults, so symptoms may have variable penetrance. This variant is found compound heterozygously with more serious mutations in cases of partial biotinidase deficiency.