Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (γ-hydroxybutyric aciduria)

Abstract

Succinic semialdehyde dehydrogenase (SSADH deficiency) (MIM 271980) is a defect in gamma-aminobutyric acid catabolism, resulting in the accumulation of gamma-hydroxybutyric acid (GHB) and causing neurological and cognitive disorders of varying severity. The non-specific nature and the difficulties in detection of urinary GHB explain why this disorder is largely underdiagnosed. Of 350 patients identified worldwide, to date only six adults with SSADH deficiency have been reported in the literature. Here we describe two additional cases in brothers up to ages 26 and 28 years. This retrospective report sheds light on the clinical features of SSADH deficiency in relation to the physiopathological involvement of GHB, and tries to identify the specific neurodevelopmental pattern of this learning disability.* Features of this are: early impaired psychomotor development with hypotonia and disturbances in motor coordination; impaired development of language, mainly due to poor auditory perception; and seizures and psychotic features in late adolescence or adulthood. Moreover, narcolepsy-like symptoms could be a consistent feature of the disease.

Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies

“…Other behavioral signs include self-injurious behaviors, autistic behaviors, and hallucinations. Sleep disturbances are common, including difficulties with initiating or maintaining sleep [43,44]. Polysomnography shows prolonged latency to stage rapid eye movement (REM), decreased percentage stage REM sleep, and decreased mean sleep latency on diurnal multiple sleep latency testing, consistent with excessive daytime somnolence associated with decreased REM sleep [45].…”

Inherited disorders of gamma‐aminobutyric acid metabolism and advances in ALDH5A1 mutation identification

“…Neuropsychiatric problems tend to be the most significant in terms of reducing quality of life, and manifest as inattention and aggression in early childhood, and disabling obsessive-compulsive disorder in adolescence and beyond. 35,36 The most common sleep disturbance experienced by individuals with SSADH deficiency is insomnia. Overnight sleep studies show a decrease in the percentage of rapid eye movement (REM) sleep, and prolonged REM latency; daytime sleep studies demonstrate a decrease in mean sleep latency, consistent with excessive daytime somnolence.…”

GHB receptors - a new trend in psychopharmacology?

“…The disease is characterized mainly by delayed mental, motor and expressive language development, as well as the occurrence of seizures, hypotonia and hyperkinesis [53][54][55]. Case studies show that some of the patients also develop psychosis and/or hallucinations [53][54][55][56].…”

“…Choroba objawia się głównie opóźnionym rozwojem psychicznym, ruchowym i werbalnym, a także występowaniem napadów drgawkowych, hipotonią oraz hiperkinezą [53][54][55]. Wśród dostępnych opisów przypadków u części pacjentów odnotuje się także występowanie psychoz i/lub halucynacji [53][54][55][56].…”