Sepiapterin reductase deficiency: Report of 5 new cases

Abstract Sepiapterin reductase deficiency is a rare, under-recognized, autosomal recessively inherited disorder of neurotransmitter metabolism. Five new patients from 3 unrelated Saudi consanguineous families are reported. Symptoms began at 6 months, with delay to diagnosis averaging 8 years. All 5 patients presented with severe symptoms including axial hypotonia, dystonia, and cognitive impairment, associated with hyper-reflexia (4 patients), spasticity (4 patients), bulbar dysfunction (4 patients), and oculogyric crisis (2 patients) with diurnal fluctuation and sleep benefit. Cerebrospinal fluid neurotransmitters analysis showed a typical pattern with increased sepiapterin and increased 7,8-dihydrobiopterin. Analysis of the SPR gene identified 3 novel mutations: c.1A>G, c.370T>C, and c.527C>T. Patient one, with early diagnosis, is currently developing within the normal range. The 4 other patients showed significant improvement in their motor function, but only mild improvement in their cognitive dysfunction. Our cases illustrate the difficulties in the diagnosis of sepiapterin reductase deficiency in infancy, and the importance of early recognition and management.