title: Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and B-cell immunity.
abstract: Three siblings presented in early childhood with central-nervous-system (CNS) dysfunction, candida dermatitis, keratoconjunctivitis, and alopecia. Two were studied immunologically and had absent delayed-hypersensitivity skin-test responses and absent in-vitro lymphocyte responses to candida antigen. One of them had selective IgA deficiency and no antibody response to pneumococcal polysaccharide immunisation, and the other had a subnormal percentage of T lymphocytes in peripheral blood. The first two siblings died with progressive CNS deterioration and overwhelming infection. The third child, who presented with a periorificial candida dermatitis, alopecia, keratoconjunctivitis, and intermittent ataxia at eighteen months of age, had intermittent lactic acidosis and raised excretion of beta-hydroxyproprionate, methylcitrate, beta-methylcrotonylglycine, and beta-hydroxyisovalerate in urine. After four days of oral biotin, 10 mg/per day, the metabolites in her urine were significantly reduced, suggesting a biotin-responsive multiple carboxylase deficiency. These findings, taken with previous reports of immune defects in patients with disorders of branched-chain aminoacid catabolism, suggest a new biochemical basis for primary immunodeficiency disease.
mesh_terms: D000505:Alopecia / Q000209:etiology; D001402:B-Lymphocytes / Q000276:immunology*; D001710:Biotin / Q000627:therapeutic use; D002179:Candidiasis, Cutaneous / Q000209:etiology; D002262:Carboxy-Lyases / Q000172:deficiency*; D002524:Cerebellar Ataxia / Q000209:etiology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D007223:Infant; D007637:Keratoconjunctivitis / Q000209:etiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001710:Biotin; D002262:Carboxy-Lyases