Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

Abstract

Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life.

Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information.

Results: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder.

Conclusions: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent.

Figure 1. MRI images

Brain MRI images of a patient with succinic semialdehyde dehydrogenase deficiency at age 62. (A) Axial T2-weighted image showing increased T2 signal intensity in the bilateral dentate nuclei of the cerebellum (arrows). (B, C) Axial T2-weighted sequences showing increased signal intensity of the bilateral globi pallidi (arrows in B and dotted lines in C). Of note, there are dilated perivascular spaces and chronic lacunes in both basal ganglia, left greater than right. (D) Axial fluid-attenuated inversion recovery (FLAIR) sequence showing parenchymal volume loss more than expected for age.

Figure 2. Distribution of current age or age at death and age at diagnosis of patients in SSADH deficiency database (n = 95)

Age distribution of patients in the succinic semialdehyde dehydrogenase (SSADH) deficiency database at time of diagnosis and in February 2015 or at time of death.