Multiple carboxylase deficiency
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
Holocarboxylase synthetase deficiency and defects in the other carboxylases are often detected by neonatal screening programs analyzing organic acids.
D81.819 – Biotin-dependent carboxylase deficiency, unspecified
8808004 – Biotinidase deficiency
- 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
- Infantile psoriasis
- Atopic dermatitis
- Netherton syndrome – Should be considered because of extensive skin involvement and alopecia.
- Langerhans cell histiocytosis
- Necrolytic migratory erythema (see glucagonoma syndrome) – Almost never occurs in children.
- Staphylococcal scalded skin syndrome
- 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.
Metabolic findings include consideration of other enzyme deficiencies such as those of urea cycle enzymes.