title: Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up.
abstract: Sepiapterin reductase (SR) catalyses the last step in the tetrahydrobiopterin biosynthesis pathway; it converts 6-pyruvoyl-tetrahydropterin (6-PTP) to BH(4) in an NADPH-dependent reaction. SR deficiency is a very rare autosomal recessive disorder with normal phenylalanine (Phe) concentration in blood and diagnostic abnormalities are detected in CSF. We present a 16-month-old girl with SR deficiency. From the newborn period she presented with an adaptation regulatory disorder. At the age of 3 months, abnormal eye movements with dystonic signs and at 4.5 months psychomotor retardation were noticed. Since that time axial hypotonia with limb spasticity (or rather delayed reflex development), gastro-oesophageal reflux and fatigue at the end of the day has been observed. Brain MRI was normal; EEG was without epileptiform discharges. Analysis of biogenic amine metabolites in CSF at the age of 16 months showed very low HVA and 5-HIAA concentrations. Analysis of CSF pterins revealed strongly elevated dihydrobiopterin (BH(2)), slightly elevated neopterin and elevated sepiapterin levels. Plasma and CSF amino acids concentrations were normal. A phenylalanine loading test showed increased Phe after 1 h, 2 h and 4 h and very high Phe/Tyr ratios. SR deficiency was confirmed in fibroblasts and a novel homozygous g.1330C>G (p.N127K) SPR mutation was identified. On L-dopa and then additionally 5-hydroxytryptophan, the girl showed slow but remarkable progress in motor and intellectual ability. Now, at the age of 3 years, she is able to sit; expressive speech is delayed (to 1 1/2 years), passive speech is well developed. Her visual-motor skills, eye-hand coordination and social development correspond to the age of 2 1/2 years.
authors.affiliation: Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-830, Warsaw, Poland. k_skoczynska@wp.pl
authors.forename: K
authors.initials: K
authors.lastname: Kusmierska
authors.forename: E E W
authors.initials: EE
authors.lastname: Jansen
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: K
authors.initials: K
authors.lastname: Szymanska
authors.forename: E
authors.initials: E
authors.lastname: Malunowicz
authors.forename: D
authors.initials: D
authors.lastname: Meilei
authors.forename: B
authors.initials: B
authors.lastname: Thony
authors.forename: N
authors.initials: N
authors.lastname: Blau
authors.forename: J
authors.initials: J
authors.lastname: Tryfon
authors.forename: D
authors.initials: D
authors.lastname: Rokicki
authors.forename: E
authors.initials: E
authors.lastname: Pronicka
authors.forename: J
authors.initials: J
authors.lastname: Sykut-Cegielska
mesh_terms: D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000429:Alcohol Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D001679:Biogenic Amines / Q000378:metabolism; D002675:Child, Preschool; D004421:Dystonia / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D020125:Mutation, Missense; D011596:Psychomotor Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology
chemical_list: D001679:Biogenic Amines; D007980:Levodopa; D006916:5-Hydroxytryptophan; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase