The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients.
OBJECTIVE
To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients.


METHODS
The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families.


METHODS
The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients.


CONCLUSIONS
Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.
Gibson
K M
KM
Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX 75226, USA.
Christensen
E
E
Jakobs
C
C
Fowler
B
B
Clarke
M A
MA
Hammersen
G
G
Raab
K
K
Kobori
J
J
Moosa
A
A
Vollmer
B
B
Rossier
E
E
Iafolla
A K
AK
Matern
D
D
Brouwer
O F
OF
Finkelstein
J
J
Aksu
F
F
Weber
H P
HP
Bakkeren
J A
JA
Gabreels
F J
FJ
Bluestone
D
D
Barron
T F
TF
Beauvais
P
P
Rabier
D
D
Santos
C
C
Lehnert
W
W
D000293:Adolescent; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology; D003937:Diagnosis, Differential; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology*; D007805:Language Development Disorders / Q000209:etiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000145:classification / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D009048:Motor Skills; D012978:Sodium Oxybate / Q000652:urine*; D050644:Succinate-Semialdehyde Dehydrogenase; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase; D020888:Vigabatrin