title: Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency.
abstract: This study aimed to investigate the clinical variability and factors implied in the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency (PTPSd). Biochemical and clinical phenotype, treatment variables, and 6-pyruvoyl-tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19 Italian patients (12 males and 7 females, aged 4 months to 33 years). According to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis, the patients were classified as mild (6) (normal level) or severe (13) (abnormal low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053 micromol/l in MF (mean +/- SD: 698 +/- 403) and 342-2120 micromol/l in SF (mean +/- SD: 1175 +/- 517) (p = 0.063). Patients with MF showed a normal neurological development (a transient dystonia was detected in one), while all SF patients except one presented with severe neurological impairment and only four had a normal neurological development. The outcome of the SF was influenced by the precocity of the treatment. Serial CSF examinations revealed a decline of 5-hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17 different mutations (seven so far unreported) (only one affected allele was identified in three subjects). A good correlation was found between genotype and clinical and biochemical phenotype. The occurrence of brain neurotransmitter deficiency and its early correction (by the therapy) are the main prognostic factors in PTPSd.
authors.affiliation: Department of Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. vincenzo.leuzzi@uniroma1.it
authors.forename: V
authors.initials: V
authors.lastname: Leuzzi
authors.forename: C A
authors.initials: CA
authors.lastname: Carducci
authors.forename: C L
authors.initials: CL
authors.lastname: Carducci
authors.forename: S
authors.initials: S
authors.lastname: Pozzessere
authors.forename: A
authors.initials: A
authors.lastname: Burlina
authors.forename: R
authors.initials: R
authors.lastname: Cerone
authors.forename: D
authors.initials: D
authors.lastname: Concolino
authors.forename: M A
authors.initials: MA
authors.lastname: Donati
authors.forename: L
authors.initials: L
authors.lastname: Fiori
authors.forename: C
authors.initials: C
authors.lastname: Meli
authors.forename: A
authors.initials: A
authors.lastname: Ponzone
authors.forename: F
authors.initials: F
authors.lastname: Porta
authors.forename: P
authors.initials: P
authors.lastname: Strisciuglio
authors.forename: I
authors.initials: I
authors.lastname: Antonozzi
authors.forename: N
authors.initials: N
authors.lastname: Blau
mesh_terms: D000293:Adolescent; D000328:Adult; D001679:Biogenic Amines / Q000134:cerebrospinal fluid; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010661:Phenylketonurias / Q000175:diagnosis; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001679:Biogenic Amines; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase