|| Biotinidase deficiency; note ability to treat & variable penetrance
|| Carrier of a biotinidase deficiency mutation
|| common in clinvar
rs13078881, also known as c.1330G>C, p.Asp444His and D444H, represents a mutation in the BTD gene on chromosome 3.
Inherited recessively, the rs13078881(C) allele is considered by ClinVar (and BabySeq) as a pathogenic mutation for biotinidase deficiency. However, it appears as if the D444H mutation results in 48% of normal enzyme activity, and if found in combination with a BTD gene mutation associated with profound deficiency, may result in partial biotinidase deficiency.[PMID 9654207]
Note that this condition is treatable; children with biotinidase deficiency identified early enough should remain asymptomatic if biotin therapy is instituted early.
|?|| (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.