TY - JOUR
T1 - Long-term follow-up of Chinese patients who received delayed treatment for 6-pyruvoyl-tetrahydropterin synthase deficiency
AU - Lee, Ni Chung
AU - Cheng, Ling Yee
AU - Liu, Tze Tze
AU - Hsiao, Kwang Jen
AU - Chiu, Pao Chin
AU - Niu, Dau Ming
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
KW - 6-Pyruvoyl-tetrahydropterin synthase deficiency
KW - Atypical penylketonuria
KW - Hyperphenylalaninemia
KW - L-DOPA
KW - Tetrahydrobiopterin
KW - hydroxytryptophan
UR - http://www.scopus.com/inward/record.url?scp=32044452704&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2005.09.028
DO - 10.1016/j.ymgme.2005.09.028
M3 - Article
C2 - 16364672
AN - SCOPUS:32044452704
SN - 1096-7192
VL - 87
SP - 128
EP - 134
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 2
ER -