Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients.
BACKGROUND
Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology.


METHODS
We overview the phenotype of 33 adolescents and adults (10.1-39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data.


RESULTS
Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14% from 2-4 years of age, mean age at first symptoms was 11+/-12 months. However, mean age at diagnosis was 6.6+/-6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had >or=3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized.


CONCLUSIONS
The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.
Knerr
Ina
I
Department of Neurology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC, USA.
Gibson
K Michael
KM
Jakobs
Cornelis
C
Pearl
Phillip L
PL
D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D001259:Ataxia / Q000209:etiology; D001526:Behavioral Symptoms / Q000209:etiology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000209:etiology; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology; D007805:Language Development Disorders / Q000209:etiology; D008297:Male; D012640:Seizures / Q000209:etiology; D012893:Sleep Wake Disorders / Q000209:etiology; D012978:Sodium Oxybate / Q000652:urine*; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency*; D011795:Surveys and Questionnaires; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; D050644:Succinate-Semialdehyde Dehydrogenase