Biotinidase Deficiency
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.Incidence
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 1:120Prenatal 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
- Contact the family and evaluate the infant for poor feeding, lethargy, or hypotonia.
- Provide emergency treatment/referral if symptoms are present (see the ACT Sheet for Biotinidase deficiency).
- To confirm the diagnosis, work with the following service(s): Newborn Screening Services (see ID providers [23]).
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Genetics (see ID providers [4]).
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
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, and links to support.
Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; 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)
Clearinghouse for local, state, and national newborn screening education, programs, policies, and resources. Also, provides
many ways for people to connect and share their viewpoints and questions about newborn screening; supported by the U.S. Department
of Health and Human Services.
Tools
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (
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 for Patients & Families in Idaho (ID)
| Service Categories | # of providers* in: | ID | NW | Other states (5) (show) | | MT | NM | NV | RI | UT |
|---|---|---|---|---|---|---|---|---|---|---|
| Newborn Screening Services | 23 | 1 | 4 | 2 | 2 | 1 | 3 | |||
| Pediatric Genetics | 4 | 1 | 7 | 4 | 4 | 4 | 6 | |||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Helpful Articles
PubMed search on biotinidase deficiency and neonatal screening, last 8 years.
Wolf B.
Clinical issues and frequent questions about biotinidase deficiency.
Mol Genet Metab.
2010;100(1):6-13.
PubMed abstract