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.
