SSADH deficiency is a rare inherited metabolic disease characterized by the metabolic disorder of GABA. The incidence rate is unknown but has been estimated at 1:100000 [
1]. The first case was reported by Jakobs in 1981 [
13]
. Parental consanguinity has been reported in approximately 40% of affected population [
9]. The median age at diagnosis of SSADH is 2 years old, but underdiagnosis is suspected [
14]. Nearly 80% of patients are diagnosed at the age of 5 years, although a few ones are confirmed in late childhood or adolescence [
14], and sporadic patients are diagnosed during adulthood [
15]. In this study, patient 3 was born to consanguineous parents. These four Chinese patients were diagnosed at the age range of 86 days to 5 years. The signs and symptoms of SSADH deficiency are often non-specific, including developmental delay, hypotonia, hyporeflexia, ataxia, neuropsychiatric problems, and epilepsy. Hypotonia and neuropsychiatric problems each have occurred in 70% of patients, and approximately half of these patients have epilepsy [
16]. Neuropsychiatric symptoms, involving disabling obsessive compulsive disorder and anxiety in addition to inattention, hyperactive behavior, and sleep disturbances, were also noted [
17]. EEG shows generalized spike-waves, photosensitivity discharge, and sleep spindle asynchrony [
18]. In this study, patients 1 and 2 presented with convulsions, and all the patients had the history of developmental delay. Patient 4 displayed hypotonia and hyporeflexia. Patient 2 and 4 exhibited decreased attention and sleep disturbances, respectively. EEG showed the background of epilepsy in patient 1 and the disappearance of sleep spindle in patient 2. The clinical manifestations of these patients are consistent with the signs and symptoms of SSADH deficiency.
SSADH deficiency is diagnosed based on the elevated GHB and 4, 5DHHA by urinary organic acid analysis. SSADH activity or molecular genetic analysis of
ALDH5A1 gene are used to confirm this disorder [
4]. In this study, the GHB in urine was elevated dramatically in these four Chinese patients. Genetic investigation also identified five mutations of
ALDH5A1 gene. Cerebral MRI showed symmetrical hyperintense signal of bilateral globus pallidus and basal ganglia in patient 1; hyperintensity of bilateral frontal-parietal lobe, widened ventricle, and sulci in patient 2; and widened ventricle and sulci in patient 4.