Long-term follow-up of Chinese patients who received delayed treatment for 6-pyruvoyl-tetrahydropterin synthase deficiency.
OBJECTIVE
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.


METHODS
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.
Lee
Ni-Chung
NC
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Cheng
Ling-Yee
LY
Liu
Tze-Tze
TT
Hsiao
Kwang-Jen
KJ
Chiu
Pao-Chin
PC
Niu
Dau-Ming
DM
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001708:Biopterins / Q000031:analogs & derivatives / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy*; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency* / Q000235:genetics; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors
D001708:Biopterins; D007980:Levodopa; D010649:Phenylalanine; D006916:5-Hydroxytryptophan; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin