Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency

Abstract

Succinic semialdehyde dehydrogenase (SSADH; E.C. 1.2.1.24) deficiency (MIM#271980) is a rare defect of the gamma-aminobutyric acid (GABA) catabolic pathway, resulting in 4-hydroxybutyric acid (GHB) accumulation.1 We report the occurrence of an unusual paroxysmal movement disorder in two affected siblings born of healthy nonconsanguineous Italian parents. This 18-year-old boy presented during childhood with autism, motor stereotypies (trunk swinging), hyperactivity, clumsiness, and hypotonia. Generalized epilepsy manifested at age 7 years, and sleep disorder (compulsive limb movements) manifested at age 10 years. Starting from age 15 years, he had a transient discomfort in the lower limbs while walking. On examination at age 16 years, he presented severe mental retardation, dysarthria, motor stereotypies (chaotic gesticulation, trunk swinging), mild dystonic postures of upper limbs, and paroxysmal exercise-induced dystonia (PED). PED emerged after approximately 100 steps as large amplitude abductor movements of the legs, gait freezing, frightful expression, and occasionally, falling (video E-1 on the Neurology Web site at www.neurology.org); he was able to walk again after resting 5 to …