TY - JOUR
T1 - MULTIPLE BIOTIN-DEPENDENT CARBOXYLASE DEFICIENCIES ASSOCIATED WITH DEFECTS IN T-CELL AND B-CELL IMMUNITY
AU - Cowan, Morton J.
AU - Packman, Seymour
AU - Wara, Diane W.
AU - Ammann, Arthur J.
AU - Yoshino, Makoto
AU - Sweetman, Lawrence
AU - Nyhan, William
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 1979/7/21
Y1 - 1979/7/21
N2 - 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 β-hydroxypropionate, methylcitrate, β-methylcrotonylglycine, and β-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.
AB - 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 β-hydroxypropionate, methylcitrate, β-methylcrotonylglycine, and β-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.
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U2 - 10.1016/S0140-6736(79)90002-3
DO - 10.1016/S0140-6736(79)90002-3
M3 - Article
C2 - 88554
AN - SCOPUS:0018748386
SN - 0140-6736
VL - 314
SP - 115
EP - 118
JO - The Lancet
JF - The Lancet
IS - 8134
ER -