Multiple Carboxylase Deficiency

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Clinical Multiple Carboxylase Deficiency

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Synonym

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Biotinidase deficiency

Holocarboxylase synthetase deficiency

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Inheritance


Prenatal

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Both autosomal recessive; holocarboxylase synthetase (HLCS) gene on 21 q22;
biotinidase (BTD) gene on 3p25


CVS/amniocentesis: biotinidase or holocarboxylase synthetase assay

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Incidence

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Biotinidase deficiency: 1:70,000 to 80,000; M=F
Holocarboxylase synthetase deficiency: unknown, rare: M=F

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Age at Presentation

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Biotinidase deficiency: approximately 6 months old
Holocarboxylase synthetase deficiency: first few days to months of life

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Pathogenesis

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Mutations in HLCS or BTD render the patient deficient in holocarboxylase synthetase or biotiniclase respectively, resulting in decreased free serum biotin and metabolic acidosis with resultant phenotype

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Clinical

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Skin
Periorificial/generalized dermatitis with/without candida infection

Hair
Sparse to total alopecia

Central Nervous System
Hypotonia, seizures, ataxia, coma

Gastrointestinal
Vomiting (holocarboxylase synthetase deficiency)

Eyes
Optic atrophy (biotinidase deficiency)

Ear Nose Throat
High frequency hearing loss (biotinidase deficiency)

Metabolism
Metabolic acidosis, hyperammonernia, organic aciduria

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D/Dx

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Atopic dermatitis

Seborrheic dermatitis

Acrodermatitis enteropathica (p. 328)

Mucocutaneous candidiasis

Essential fatty acid deficiency

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Lab

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Screen urine for organic aciduria

Serum biotinidase/holocarboxylase synthetase assay

Screen blood metabolic acidosis, hyperammonemia

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Management

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Biotin 10 mg per day for life

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Prognosis

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If biotin instituted prior to neurologic sequelae, normal life span with normal growth and development