title: Sepiapterin reductase deficiency: Report of 5 new cases.
abstract: BACKGROUND
  Sepiapterin reductase deficiency is a rare, under-recognized, autosomal recessively inherited disorder of neurotransmitter metabolism.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Our cases illustrate the difficulties in the diagnosis of sepiapterin reductase deficiency in infancy, and the importance of early recognition and management.
authors.affiliation: Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Sarah
authors.initials: S
authors.lastname: AlSubhi
authors.affiliation: Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Saad
authors.initials: S
authors.lastname: AlShahwan
authors.affiliation: Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: AlMuhaizae
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hamed
authors.initials: H
authors.lastname: AlZaidan
authors.affiliation: Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Electronic address: btabarki@hotmail.com.
authors.forename: Brahim
authors.initials: B
authors.lastname: Tabarki
mesh_terms: D000293:Adolescent; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D001708:Biopterins / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D002648:Child; D057210:Delayed Diagnosis; D004421:Dystonia / Q000134:cerebrospinal fluid / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000235:genetics*; D009154:Mutation; D011596:Psychomotor Disorders / Q000134:cerebrospinal fluid / Q000235:genetics*; D011622:Pterins / Q000134:cerebrospinal fluid
chemical_list: D011622:Pterins; D001708:Biopterins; C017226:7,8-dihydrobiopterin; C016727:sepiapterin; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase
keywords: CSF neurotransmitters; Hypotonia; Oculogyric crisis; Sepiapterin reductase deficiency