THE CLINICAL PHENOTYPE OF SUCCINIC SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY (4-HYDROXYBUTYRIC ACIDURIA) - CASE-REPORTS OF 23 NEW PATIENTS

Objectives. 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 pati ents with (idiopathic) mental retardation and emphasize the need for a ccurate, quantitative organic acid analysis in such patients. Patients . The clinical features of 23 patients (20 families) with SSADH defici ency (4-hydroxybutyric aciduria) are presented. The age at diagnosis r anged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): mot or delay, including fine-motor skills, 78%; language delay, 78%; hypot onia, 74%; mental delay, 74%; seizures, 48%; decreased or absent refle xes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; ne onatal 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 deg rees 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 dev elopment. Our recommendation would be that accurate, quantitative orga nic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, moto r, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis c an be confirmed by determination of enzyme activity in white cells fro m whole blood. We think that increased use of organic acid determinati on will lead to increased diagnosis of SSADH deficiency and a more acc urate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metaboli c and clinical profiles of SSADH deficiency.