Succinic semialdehyde dehydrogenase (SSADH) deficiency is arare autosomal recessive disorder of the GABA pathway. Due to the heterogeneity of neurological clinical symptoms, including mental retardation, speech delay, seizures, ataxia, movement disorders, it is often undiagnosed unless organic acids analysis is performed. Vigabatrin may be helpful to reduce the amount of toxic metabolite (4-hydroxybutiric acid, GHB). We describe a 6 years old girl affected by SSADH deficiency from an Italian family in which we found a novel mutation in ALDH5A1 gene. The child presented only mild mental retardation with severe speech delay. Basal neurometabolic work-up, usually performed in our Department for patients with similar picture, showed an increase of GHB excretion (311 μmol/mmol creatine; controls < 5), while the other exams were normal. The diagnosis of SSADH deficiency was suspected and MRI-1H-MRS showed signal abnormalities involving globus pallidus, subcortical white matter and cerebellar dentate nuclei. SSADH activity in patient’s lymphocytes was strongly decreased (48 pmol/min/mg pro; controls 1907–3901 pmol/min/mg pro); two pathogenic mutations have been identified in the ALDH5A1 gene: c.278G>T in exon 1 and a new mutation in exon 10 (c.1557T>G) and in the pedigree. Treatment with Vigabatrin at low doses (25mg/Kg/die) significantly reduced GHB levels in biological fluids including CSF, with a concomitant increase of GABA, and a clinical improvement throughout the two years of follow-up was observed. In conclusion we suggest that SSADH deficiency should be considered in the differential diagnosis of patients with mental retardation and language delay being likely a presentation of mild phenotype.
SSADH deficiency: a new mutation associated to a mild phenotype in an Italian girl
Cioni G;Battini R
2010-01-01
Abstract
Succinic semialdehyde dehydrogenase (SSADH) deficiency is arare autosomal recessive disorder of the GABA pathway. Due to the heterogeneity of neurological clinical symptoms, including mental retardation, speech delay, seizures, ataxia, movement disorders, it is often undiagnosed unless organic acids analysis is performed. Vigabatrin may be helpful to reduce the amount of toxic metabolite (4-hydroxybutiric acid, GHB). We describe a 6 years old girl affected by SSADH deficiency from an Italian family in which we found a novel mutation in ALDH5A1 gene. The child presented only mild mental retardation with severe speech delay. Basal neurometabolic work-up, usually performed in our Department for patients with similar picture, showed an increase of GHB excretion (311 μmol/mmol creatine; controls < 5), while the other exams were normal. The diagnosis of SSADH deficiency was suspected and MRI-1H-MRS showed signal abnormalities involving globus pallidus, subcortical white matter and cerebellar dentate nuclei. SSADH activity in patient’s lymphocytes was strongly decreased (48 pmol/min/mg pro; controls 1907–3901 pmol/min/mg pro); two pathogenic mutations have been identified in the ALDH5A1 gene: c.278G>T in exon 1 and a new mutation in exon 10 (c.1557T>G) and in the pedigree. Treatment with Vigabatrin at low doses (25mg/Kg/die) significantly reduced GHB levels in biological fluids including CSF, with a concomitant increase of GABA, and a clinical improvement throughout the two years of follow-up was observed. In conclusion we suggest that SSADH deficiency should be considered in the differential diagnosis of patients with mental retardation and language delay being likely a presentation of mild phenotype.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
