7-8-dihydrobiopterin and Metabolism--Inborn-Errors

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.

Topics: Adolescent; Alcohol Oxidoreductases; Biopterins; Child; Delayed Diagnosis; Dystonia; Female; Humans; Infant; Male; Metabolism, Inborn Errors; Mutation; Psychomotor Disorders; Pterins

For the last 2 years, a program has been developed to screen all hyperphenylalaninemic babies for tetrahydrobiopterin deficiency, by measurement of pterins in urine. High neopterin and low biopterin levels were found in the urine of a 1-month-old girl. Further investigations confirmed an impaired conversion of neopterin to biopterin. No neurological signs were noted, but, in regard to the laboratory data, neurotransmitter replacement therapy was instituted at 2.5 months of age. The most remarkable feature was a rapid increase in the dietetic phenylalanine tolerance, despite the proof that the child was not able to clear a challenging dose of phenylalanine and the record of unchanged pathologically low excretion of biopterin during a 2 month period.

Topics: Biopterins; Female; Humans; Infant; Infant, Newborn; Metabolism, Inborn Errors; Neopterin; Phenylalanine; Pteridines