Biotinidase Deficiency via the BTD Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9551 BTD 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9551BTD81404 81404, 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Multiple carboxylase deficiency (MCD) is an inborn error of metabolism resulting from defective biotin metabolism. Juvenile-onset (also called late-onset) MCD (OMIM #253260) results from profound or partial deficiency of biotinidase, whereas early-onset MCD (OMIM #253270) is caused by holocarboxylase synthetase deficiency. Both forms of MCD are responsive to biotin therapy. Making a distinction between the two types is difficult and relies largely on age of onset rather than clinical features. Clinical signs of juvenile-onset MCD typically appear after 3 months of age, while early-onset MCD is typically evident earlier than 3 months of age (Wolf et al. Ann Neurol 18:614-617, 1985). In vitro enzyme studies are capable of distinguishing between the two disorders. The earliest-presenting sign is usually seizures, but other early non-specific symptoms include hypotonia, respiratory symptoms, developmental delay, and ataxia. Eczema, alopecia, dermatitis, and skin infections are also common findings, and cutaneous presentations in conjunction with neurological symptoms greatly limit the differential diagnosis. Clinical variability is documented. Untreated patients with partial biotinidase deficiency may experience fewer and milder symptoms than patients with complete deficiency (Suormala et al. J Inher Metab Dis 13:76-92, 1990). Asymptomatic adults with profound biotinidase deficiency have also been reported (Wolf et al. Am J Med Genet 73:5-9, 1997).


BTD-related multiple carboxylase deficiency (MCD) is an autosomal recessive disorder. Variants in the BTD gene (OMIM #609019) are the genetic cause of juvenile- or late-onset MCD. Over 100 BTD variants have been reported in children affected with profound biotinidase deficiency. Most pathogenic variants are missense variants, although nonsense, small insertions and deletions, and splice site variants have also been found. Three variants (p.Cys33Phefs*36, p.[Ala171Thr;Asp444His], and p.Gln456His) are commonly found in biotinidase-deficient newborns ascertained by newborn screening in the USA (Cowan et al. Genet Med 12:464-470, 2010). The p.Cys33Phefs*36 variant is found commonly in symptomatic patients (Norrgard et al. Pediatr Res 46:20-27, 1999). One other variant (p.Arg538Cys) is common among symptomatic children but not among newborns with a positive biotinidase screen (Pomponio et al. Hum Genet 99:506-512, 1997). The p.Asp444His variant reduces enzyme activity ~50% and results in a partial biotinidase deficiency when present in trans with a severe variant. The worldwide carrier frequency for BTD variants is thought to be 1 in 120 (Wolf et al. J Inherit Metab Dis 14:923-927, 1991).

Testing Strategy

This test provides full coverage of all coding exons of the BTD gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Pomponio et al. (Pediat Res 42:840-848, 1997) identified variants on each BTD allele in all 30 biotinidase-deficient probands analyzed. The p.Arg538Cys and p.Cys33Phefs*36 variants accounted for over 50% of the mutant alleles in this study.

Indications for Test

Patients suspected of having multiple carboxylase deficiency based on biochemical testing and/or clinical features. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BTD.


Official Gene Symbol OMIM ID
BTD 609019
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Multiple Carboxylase Deficiency, Juvenile Onset AR 253260


  • Cowan, T. M., (2010). "Technical standards and guidelines for the diagnosis of biotinidase deficiency." Genet Med 12(7): 464-70. PubMed ID: 20539236
  • Norrgard, K. J., (1999). "Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children." Pediatr Res 46(1): 20-7. PubMed ID: 10400129
  • Pomponio, R. J., (1997). "Arg538 to Cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children." Hum Genet 99(4): 506-12. PubMed ID: 9099842
  • Pomponio, R. J., (1997). "Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis." Pediatr Res 42(6): 840-8. PubMed ID: 9396567
  • Suormala, T. M., (1990). "Comparison of patients with complete and partial biotinidase deficiency: biochemical studies." J Inherit Metab Dis 13(1): 76-92. PubMed ID: 2109151
  • Wolf, B. (1991). "Worldwide survey of neonatal screening for biotinidase deficiency." J Inherit Metab Dis 14(6): 923-7. PubMed ID: 1779651
  • Wolf, B., (1985). "Biotinidase deficiency: initial clinical features and rapid diagnosis." Ann Neurol 18(5): 614-7. PubMed ID: 4073853
  • Wolf, B., (1997). "Profound biotinidase deficiency in two asymptomatic adults." Am J Med Genet 73(1): 5-9. PubMed ID: 9375914


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

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STAT and Prenatal Test Options are not available with Patient Plus.

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