Long-term follow-up of Chinese patients who received delayed treatment for 6-pyruvoyl-tetrahydropterin synthase deficiency
Journal
Molecular Genetics and Metabolism
Journal Volume
87
Journal Issue
2
Pages
128-134
Date Issued
2006
Author(s)
Abstract
Objectives: 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is the most important type of BH4 deficiency related to hyperphenylalaninemia. PTPS deficiency may not only cause a typical phenylketonuric phenotype, but is also accompanied by various neurological signs and symptoms due to impaired synthesis of catecholamines and serotonin. Reports of the long-term outcomes of these patients, especially after delayed onset of therapy, are few. Study design: We reviewed the characteristics of 10 PTPS-deficient patients whose treatment onset with tetrahydrobiopterin, l-DOPA, and hydroxytryptophan had been delayed. The relationships among clinical manifestations, biochemical findings, genotypes, and long-term outcomes were analyzed. Results: We classified eight patients as having severe forms, and two as having moderate forms of PTPS deficiency. Improvements in neurological status and intelligence/developmental quotient (IQ/DQ) were observed in all patients, up to approximately 15 years of follow-up. One patient began walking and talking after 4 years of treatment. In patients with severe disease, the mean initial IQ/DQ was 45.40 ± 13.94, and the final full-scale intelligence quotient (FIQ) score was 62.8 ± 13.06 (p = 0.042), with a mean increment of 17.4 ± 5.27 over 15.86 ± 4.85 years of follow-up. Two patients with moderately severe disease had FIQ increases from 75 to 77 and from 76 to 80 points, respectively. Conclusions: The administration of neurotransmitters based on clinical response and adverse effects was beneficial in patients whose treatment of PTPS deficiency was delayed. Sustained clinical improvements were observed up to 15 years of follow-up. ? 2005 Elsevier Inc. All rights reserved.
Subjects
6-Pyruvoyl-tetrahydropterin synthase deficiency; Atypical penylketonuria; hydroxytryptophan; Hyperphenylalaninemia; L-DOPA; Tetrahydrobiopterin
SDGs
Other Subjects
5 hydroxytryptophan; 6 pyruvoyltetrahydropterin synthase; carbidopa; catecholamine derivative; levodopa; serotonin; tetrahydrobiopterin; 6 pyruvoyltetrahydropterin synthase deficiency; adolescent; adult; child; China; clinical article; clinical feature; controlled study; diarrhea; disease severity; dose response; enzyme deficiency; enzyme synthesis; female; follow up; genotype; human; hyperphenylalaninemia; infant; insomnia; intelligence quotient; irritability; long term care; male; motor development; motor dysfunction; priority journal; review; side effect; therapy delay; treatment outcome; vomiting
Publisher
Academic Press Inc.
Type
journal article