BIOTINIDASE DEFICIENCY

BTD sequencing

MITOCHONDRIAL DNA ANALYSIS

Also see: Biotinidase - Biochemical Analysis

Biotin is the essential coenzyme for four biotin-dependent carboxylases in humans: pyruvate carboxylase, propionyl CoA carboxylase, b -methylcrotonyl CoA carboxylase, and acetyl CoA carboxylase. These enzymes have important roles in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotinidase deficiency (MIM 253260), also known as late-onset (juvenile) multiple carboxylase deficiency, is a disorder of biotin recycling. In the untreated state, profound biotinidase deficiency is usually initially characterized by seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities such as alopecia, skin rash, and tendency to fungi infection. With age, motor limb weakness, spastic paresis, and decreased visual acuity occur. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress. Biotinidase deficiency can be diagnosed by demonstrating deficient enzyme activity in serum. BTD gene sequencing is most useful when the results of enzymatic testing are ambiguous, such as in differentiating profound biotinidase deficiency from partial biotinidase deficiency or heterozygous carriers. BTD1 gene maps to chromosome 3p25.1. It contains 4 coding exons, and encodes for a protein of 543 amino acids.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing

Testing Methodology:

The exons and flanking intronic regions of the BTD gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc.
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83891, 83904x8, 83898x4, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition

References:

Pindolia K, Jensen K, Wolf B. Three dimensional structure of human biotinidase: computer modeling and functional correlations. Mol Genet Metab. 2007; 92: 13-22.
Wolf B, Jensen KP, Barshop B, et al. Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. Hum Mutat. 2005; 25 (4):413.
László A, Schuler EA, Sallay E, et al. Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies. J Inherit Metab Dis. 2003; 26 (7):693-8.

Test Codes:

Index: 3495
Known Familial Mutation: 3496