Home > Newborn Disorders > Biotinidase deficiency
Biotinidase deficiency
Overview
The result of a mutation of the BTD gene which is responsible for making biotinidase which, in turn, is responsible for extraction of biotin from ingested sources and recycling of biotin from endogenous sources. 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.Prevalence
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 1/120Clinical 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; and
- ataxia.
Older children may manifest:
- limb weakness;
- paresis;
- developmental delay;
- neurosensory hearing loss;
- optic atrophy and scotomata; and
- 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 on positive screening test
Quantitative enzyme assay on serum/plasma specimen. Testing of siblings of affected patients to identify those at risk for late onset symptoms. Targeted DNA anyalysis for 5 common mutations can identify a specific mutation responsible for partial biotinidase deficiency (p.D444H) and about 60% of disease-causing mutations. 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;
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-581-8943); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Biotinidase deficiency tutorial for parents, English & Spanish for additional information);
- Start oral biotin at 5mg bid and assure continuation for 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 Management
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, Utah Newborn Screening Program Newsletter
(
226 KB)
Five pages of detail on biotinidase deficiency, including screeing, pathophysiology, management, and Quick Facts.
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG)
( 400 KB)
Developed by the American College of Medical Genetics, includes recommended responses to positive newborn screening test results,
diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory
Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Biotinidase deficiency (GeneReviews)
Detailed review by Barry Wolf, MD, PhD, including clinical description, natural history, management, and genetics.
Resources for Biotinidase deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
For Parents and Patients
Biotinidase deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Biotinidase deficiency tutorial for parents, English & Spanish
From the Iowa Department of Health's Center for Congenital and Inherited Disorders web site, click the link for "Patient Education
Learning Modules" for several tutuorials on congenital conditions from the Patient Education Institute. Please let us know
if this link disappears or no longer works.
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.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (4) 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 in the last 5 years.
Wolf B.
Clinical issues and frequent questions about biotinidase deficiency.
Mol Genet Metab.
2010;100(1):6-13.
PubMed abstract
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 7/2010 |