TY - JOUR
T1 - Succinic semialdehyde dehydrogenase deficiency
T2 - an inborn error of gamma-aminobutyric acid metabolism
AU - Gibson, Kenneth M.
AU - Sweetman, Lawrence
AU - Nyhan, William L.
AU - Jakobs, Cornells
AU - Rating, Dietz
AU - Siemes, Hartmut
AU - Hanefeld, Folker
N1 - Funding Information:
This work was supportedi n part by U.S. Public Health ServicesG rant No. HD-04608 from the National Institute of Child Health and Human Development, and Grant No. GM - 17702 from the National Institute of SciencesN, ational Instituteso f Health, BethesdaM, D, USA.
PY - 1983/9/15
Y1 - 1983/9/15
N2 - Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 ±1.9 pmol · min-1 · mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol · min-1 · mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.
AB - Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 ±1.9 pmol · min-1 · mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol · min-1 · mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.
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U2 - 10.1016/0009-8981(83)90018-9
DO - 10.1016/0009-8981(83)90018-9
M3 - Article
C2 - 6627675
AN - SCOPUS:0020620922
SN - 0009-8981
VL - 133
SP - 33
EP - 42
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1
ER -