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Screening & Prevention >> Newborn Screening >> Organic Acidemias >> Biotinidase deficiency

Biotinidase deficiency

Disorder Category

an organic acid disorder

Screening

Finding

genetic inability to unbind 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.

Names

Biotinidase deficiency

Multiple carboxylase deficiency, late-onset

ICD-9

277.6, Deficiency of circulating enzymes

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.

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 1/120

Inheritance

autosomal recessive

Maternal and Family History

Carriers can be diagnosed with 95% accuracy.

Clinical Characteristics

With treatment, clinical outcomes should be excellent. Without treatment, outcomes depend on the inherent severity of disease in the affected patient. In the severe form, with profound biotinidase deficiency (<10% of normal), neurologic injury 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. DNA anyalysis can identify 60% of disease-causing 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 (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

Links

For Professionals

Revealing Biotinidase, Utah Newborn Screening Program Newsletter (pdf 228kb)
Five pages of detail on biotinidase deficiency, including screeing, pathophysiology, management, and Quick Facts.

ACT Sheet for Biotinidase deficiency from ACMG
Developed by the American College of Medical Genetics (ACMG), 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.

ACMG ACT Sheets and Confirmatory Algorithms
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 review, GeneTests.org
Detailed review by Barry Wolf, MD, PhD, including clinical description, natural history, management, and genetics.

For Parents

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, SaveBabies.org
Brief discussion with links to more information and support groups for parents from Save Babies Though Newborn Screening Foundation, Inc.

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, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) 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.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008
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