Biotinidase Deficiency

Other Names

Multiple carboxylase deficiency, late-onset

Diagnosis Coding

D81.810, biotinidase deficiency

Disorder Category

An organic acidemia

Screening

Finding

Decreased activity of biotinidase, an enzyme that releases biotin (vitamin H) from proteins

Tested By

Colorimetric, semiquantitative enzyme assay; false positives may occur in premature infants and in samples placed in plastic before sufficient drying or exposed to excessive heat.

Overview

An inherited disorder in which the body is unable to reuse and recycle biotin, a B vitamin found in foods such as liver, egg yolks and milk. The BTD gene is responsible for making biotinidase which, in turn, is responsible for extraction of biotin from ingested dietary sources and recycling of biotin from endogenous sources (breakdown of endogenous proteins). Biotin is an essential cofactor for several carboxylase enzymes that are required to process proteins, fats, or carbohydrates. The developing brain is particularly sensitive to biotin deficiency. Patients usually appear perfectly normal at birth, but can develop irreversible hearing and vision loss if untreated.

Prevalence

Prevalence is 1:60,000 overall; 1 :130,000 for profound deficiency and 1:110,00 for partial deficiency; carrier (heterozygous for BTD mutation) frequency is about 1:120

Inheritance

Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

Other Testing

Genetic testing is possible for at-risk family members. Carriers can be diagnosed with 95% accuracy by enzyme assay, but DNA testing is superior for this purpose being less affected by temperature or sample handling.

Clinical Characteristics

With treatment, clinical outcomes are excellent. Without treatment, outcomes depend on the inherent severity of disease in the affected patient. In the severe form, with profound biotinidase deficiency (enzyme activity <10% of normal), neurologic injury, hearing loss, blindness, and death may result. Symptoms may develop as soon as the first week of life or as late as 10 years of age (mean age of 3 1/2 months).

Initial signs/symptoms may include:
  • seizures
  • hypotonia
  • hyperventilation, laryngeal stridor, and/or apnea
  • eczematoid rash
  • alopecia
  • conjunctivitis
  • candidiasis
  • ataxia

Older children may manifest:
  • limb weakness
  • paresis
  • developmental delay
  • neurosensory hearing loss
  • optic atrophy and scotomata
  • recurrent viral and fungal infections

Children with untreated partial biotinidase deficiency may manifest any of the above symptoms, though generally they will be mild and occur only with concomitant stressors, such as prolonged infection.

Follow-up Testing after Positive Screen

Quantitative enzyme assay on serum/plasma specimen. Testing of siblings of affected patients to identify those at risk for late onset symptoms. A panel of five common BTD mutations detects approximately 60% of disease-causing mutations and can identify a specific mutation responsible for partial biotinidase deficiency (p.D444H). Full-gene sequencing is available and can identify up to 99% of causative mutations.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill.
  • Start oral biotin at 5mg bid and assure continuation for life in patients with profound biotinidase deficiency. Patients with partial deficiency might require lower doses after the first year of life.
  • For those identified after irreversible consequences, assist in management, particularly with low vision aids, hearing aids or cochlear implants, developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration if the child is affected. Genetic counseling for the family. Periodic vision and hearing evaluation if indicated.

Resources

Information & Support

For Professionals

Revealing Biotinidase (UDOH) (PDF Document 226 KB)
Five pages of detail on biotinidase deficiency, including screening, pathophysiology, management, and Quick Facts; from the Utah Newborn Screening Program, Utah Department of Health

Biotinidase Deficiency (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information for the condition; National Center for Biotechnology Information, U.S. National Library of Medicine.

Resources for Biotinidase Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

Biotinidase Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

Biotinidase Deficiency Family Support Group
Support group site with information, links, and a "Family Center" with an email forum, chance to meet other families, and read stories.

Baby's First Test (Genetic Alliance)
A clearinghouse for newborn screening information. Provides resources about screening at the local, state, and national levels and ways for people to share their viewpoints and questions about newborn screening.

Tools

ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (PDF Document 400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search on biotinidase deficiency and neonatal screening, last 10 years.

Wolf B.
Clinical issues and frequent questions about biotinidase deficiency.
Mol Genet Metab. 2010;100(1):6-13. PubMed abstract

Authors

Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2007
Content Last Updated: 11/2015