Clinical and molecular features of a boy with incomplete WAGR syndrome and succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADH deficiency, MIM 271980) is a rare neurometabolic disorder of GABA metabolism. Its diagnostic hallmark is the accumulation of 4-hydroxy-butyric acid in cerebrospinal fluid and other biological fluids. SSADH is coded on chromosome 6p22 and the defect is inherited autosomal recessively. Patients show a heterogeneous clinical spectrum and may exhibit developmental delay, mental retardation, hypotonia, hyporeflexia, autistic behaviour, ataxia or seizures. As a therapeutic option, vigabatrin may be of value as it is an inhibitor of the GABA transaminase, but the results may also be disappointing possibly due to an accumulation of GABA.

WAGR syndrome is the association between Wilms tumor and aniridia, genitourinary malformations and mental retardation due to a deletion of the chromosomal region 11p13 (MIM 194072).

We describe the clinical course of a 3-year-old boy with psychomotor retardation for whom an extensive diagnostic work-up showed both those rare conditions: SSADH deficiency (no detectable activity of SSADH, novel missense mutation c.587G>A) and incomplete WAGR syndrome [karyotype 46, XY, del (11) (p13p14.2)]. Clinical features of this patient included language delay, autistic features, motor disabilities and disabilities of coordination and dexterity, he had also aniridia in both eyes and a hydrocephalus internus. Interestingly this boy, like other cases described in the literature, was obese, and obesity may be added to the WAGR spectrum. In this patient however, WT1 (Wilms' tumor) gene, functioning as a transcriptional activator or repressor for many growth factor genes, was not affected and differentiation of genitourinary tissues was therefore normal. Treatment options for this patient are limited and include supportive treatment, physiotherapy, special educational needs and, eventually, vigabatrin.