Journal Article

Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder

B. G. R. Neville, R. Parascandalo, R. Farrugia and A. Felice

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 10, pages 2291-2296
Published in print October 2005 | ISSN: 0006-8950
Published online July 2005 | e-ISSN: 1460-2156 | DOI:
Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder

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This study presents the clinical findings on seven children from Malta (population 385 000). All of them had early motor delay and a significant degree of cognitive impairment. Diurnal variation of the motor impairments was clear in six out of seven of the subjects and oculogyric crises occurred from an early stage also in six out of the seven. Five out of seven had clear evidence of dystonia but the early picture was dominated by hypotonia in five. Two had early Parkinsonian tremor and chorea was seen in four, although in two this was attributable to the use of l-dopa. Three had early bulbar involvement. In all, although minor motor problems persisted, the response to l-dopa was dramatic and there was a need to balance improvement in dystonia against aggravation of chorea. The majority were not able to walk until they were treated. Increased doses of l-dopa were required in hot weather, to which they were sensitive. Despite a good response of improved motor ability and abolition of oculogyric crises, there was no obvious change in cognitive function with learning remaining in the moderate impairment range. This report widens the phenotype of dopa-responsive motor disorders and the range of young children with primary motor delay (cerebral palsy) who need a clinical trial of l-dopa. All of the subjects had the same novel mutation in the tetrahydrobiopterin pathway involving sepiapterin reductase, and no abnormality in the gene encoding guanosine triphosphate cyclohydrolase 1. Clinically and molecularly the condition shows autosomal recessive inheritance.

Keywords: cognition; dopa responsive; l-dopa; sepiapterin reductase; ADGTPCH1 = Autosomal dominant guanosine triphosphate cyclohydrolase 1; BH4 = Tetrahydrobiopterin; SR = Sepiapterin reductase

Journal Article.  4951 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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