SEPIAPTERIN REDUCTASE DEFICIENCY: A CONGENITAL DOPA-RESPONSIVE MOTOR AND COGNITIVE DISORDER

We have described 7 patients with this apparently rare congenital motor disorder within 4 families in Malta with an identical autosomal recessively inherited novel mutation in the tetrahydrobiopterin pathway involving sepiapterin reductase (SR), with no abnormality in the gene encoding guanosine triphosphate cyclohydrolase1 (GTPCHI). Two patients with similar presentation with different abnormalities in the same gene are in the literature. The clinical features include primary severe tetraplegic motor delay dominated by hypotonia but with Parkinsonian tremor in 2, chorea in 4, and 5 out of 7 had dystonia. Oculogyric crisis were an early feature. Diurnal variation was seen and all showed a dramatic through not complete response to L-dopa. All had significant cognitive impairment which did not appear to be influenced by L-dopa treatment. However that issue has not been examined in detail in this group and there is one report of a rise in IQ on treatment with L-dopa and 5-HTP therapy. This disorder presents a quite distinct phenotype to classical Segawa disease but in physical manifestation resembles the small number of children reported with GTPCH 1 deficiency who have primary motor delay and who, like those with SR deficiency, may be diagnosed as having cerebral palsy. This disorder reinforces the need to investigate, including giving a trial of L-dopa, children with an unexplained congenital motor disorder.