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Multiple carboxylase deficiency - Skin
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Multiple carboxylase deficiency - Skin

Contributors: Jeffrey D. Bernhard MD, Craig N. Burkhart MD, Dean Morrell MD, Lowell A. Goldsmith MD, MPH, Nancy Esterly MD
Other Resources UpToDate PubMed

Synopsis

Biotin deficiency due to a recessively inherited genetic defect of biotinidase, genetic defects of several carboxylases, or holocarboxylase synthetase mutations causes profound metabolic defects that can lead to permanent nervous system damage and even death. Biotinidase releases biotin from foods or from endogenous peptides. Free biotin is essential for activating four coenzyme A (CoA)-containing or -dependent carboxylases that have essential roles in protein catabolism, fatty acid synthesis, and gluconeogenesis. Holocarboxylase synthetase incorporates biotin into the four carboxylases. Biotinidase and holocarboxylase synthetase deficiency can be treated with pharmacologic doses of oral biotin.

These deficiencies are screened for in all newborns in the United States and several other countries. Biotinidase deficiency has an overall incidence of about 1:60 000 newborns. In California, biotinidase deficiency has a higher incidence in Hispanics of Mexican descent. The disorder has been found worldwide in all populations and ethnic groups.

Biotinidase deficiency can be profound or partial; profound and partial deficiencies of biotinidase are the most common forms of the multiple carboxylase-related deficiencies.

Profound biotinidase deficiency – Mean age of onset is 3.5 months; onset often occurs by 1 week of age. If untreated, patients may develop the following:
  • Seizures (often myoclonic) and hypotonia
  • Sensorineural deafness, ataxia and optic atrophy, and developmental delay
  • Hyperventilation, respiratory stridor, and apnea
  • Alopecia (rarely, trichorrhexis changes have been reported in remaining hairs)
  • Perioral and periorificial eruptions than can be generalized, cutaneous Candida infections, and conjunctivitis
  • Metabolic changes including keto-lactic acidosis, organic aciduria and increased ammonia levels, and hypoglycemia
Partial biotinidase deficiency – Similar symptoms but to a lesser degree, and later onset or onset only with metabolic stress such as infection.

Holocarboxylase synthetase deficiency and defects in the other carboxylases are often detected by neonatal screening programs analyzing organic acids.

Codes

ICD10CM:
D81.819 – Biotin-dependent carboxylase deficiency, unspecified

SNOMEDCT:
8808004 – Biotinidase deficiency

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Differential Diagnosis & Pitfalls

Skin manifestations require consideration of the following:
  • Essential fatty acid deficiency
  • Acrodermatitis enteropathica
  • Other carboxylase deficiencies such as holocarboxylase synthetase deficiency and isolated carboxylase enzyme deficiencies – Holocarboxylase synthetase binds biotin to the carboxylases, and its autosomal recessive deficiency mimics biotinidase deficiency. Onset is in the first days to weeks of life. Very rarely, patients have the signs and symptoms of biotinidase deficiency but normal biotinidase levels; these patients respond to biotin therapy.
  • Nutritional biotin deficiency from eating large amounts of uncooked egg whites.
  • Seborrheic dermatitis
  • Scabies
  • Infantile psoriasis
Immunodeficiencies:
Other hair defects:
  • Nonscarring alopecia may suggest other genetic defects including atrichia with papular lesions due to mutations in the hairless (HR) gene and type II vitamin D-deficient rickets.
  • Diffuse alopecia may suggest iron deficiency, but iron deficiency does not have the skin changes of biotin deficiencies.
Nervous system findings require consideration of other causes of ataxia, sensorineural deafness, and optic atrophy.

Metabolic findings include consideration of other enzyme deficiencies such as those of urea cycle enzymes.

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Last Updated:11/07/2013
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Multiple carboxylase deficiency - Skin
Multiple carboxylase deficiency : Seizures, Ataxia, Hearing loss, Hypoglycemia, Metabolic acidosis, Optic disc atrophy, Scaly plaque, Alopecia, Stridor
Clinical image of Multiple carboxylase deficiency
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