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Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency.
Eur J Pediatr. 2001 May; 160(5):267-76.EJ

Abstract

The outcome of 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, the most common form of tetrahydrobiopterin (BH4) deficiency, depends on factors such as severity of the disease, type of mutation, time of diagnosis, and mode of treatment. We investigated five patients from four different families, four of them presenting with the severe form of PTPS deficiency and one with the mild peripheral form. In this study, missense (L26F, T67M, P87L, V124L, D136G, D136V) and nonsense (R15-16ins) mutations were detected by reverse transcriptase polymerase chain reaction and sequence analysis. Two patients with the severe form were compound heterozygotes (T67M/P87L and D136G/R15-16ins), two siblings were homozygous for the D136V mutation, and in the patient with the mild form, heterozygous L26F/V124L mutations were present. Two patients are on combined therapy with L-dopa/carbidopa/5-hydroxytryptophan plus BH4, the siblings are on monotherapy with BH4, and the patient with the mild form is now off treatment, presenting with normal plasma phenylalanine levels.

CONCLUSION

Long-term follow-up shows that the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency benefits from treatment started in the first months of life and that the phenotype may change with age. Additionally, depending on the type of mutations, prenatal damage to the fetus may multiply the clinical abnormalities and thus worsen the prognosis of the disease. In patients initially diagnosed with the mild peripheral form of the disease, therapy with tetrahydrobiopterin should be stopped after some time to test whether hyperphenylalaninaemia was only a transient condition.

Authors+Show Affiliations

Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11388593

Citation

Dudesek, A, et al. "Molecular Analysis and Long-term Follow-up of Patients With Different Forms of 6-pyruvoyl-tetrahydropterin Synthase Deficiency." European Journal of Pediatrics, vol. 160, no. 5, 2001, pp. 267-76.
Dudesek A, Röschinger W, Muntau AC, et al. Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. Eur J Pediatr. 2001;160(5):267-76.
Dudesek, A., Röschinger, W., Muntau, A. C., Seidel, J., Leupold, D., Thöny, B., & Blau, N. (2001). Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. European Journal of Pediatrics, 160(5), 267-76.
Dudesek A, et al. Molecular Analysis and Long-term Follow-up of Patients With Different Forms of 6-pyruvoyl-tetrahydropterin Synthase Deficiency. Eur J Pediatr. 2001;160(5):267-76. PubMed PMID: 11388593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. AU - Dudesek,A, AU - Röschinger,W, AU - Muntau,A C, AU - Seidel,J, AU - Leupold,D, AU - Thöny,B, AU - Blau,N, PY - 2001/6/5/pubmed PY - 2001/10/5/medline PY - 2001/6/5/entrez SP - 267 EP - 76 JF - European journal of pediatrics JO - Eur J Pediatr VL - 160 IS - 5 N2 - UNLABELLED: The outcome of 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, the most common form of tetrahydrobiopterin (BH4) deficiency, depends on factors such as severity of the disease, type of mutation, time of diagnosis, and mode of treatment. We investigated five patients from four different families, four of them presenting with the severe form of PTPS deficiency and one with the mild peripheral form. In this study, missense (L26F, T67M, P87L, V124L, D136G, D136V) and nonsense (R15-16ins) mutations were detected by reverse transcriptase polymerase chain reaction and sequence analysis. Two patients with the severe form were compound heterozygotes (T67M/P87L and D136G/R15-16ins), two siblings were homozygous for the D136V mutation, and in the patient with the mild form, heterozygous L26F/V124L mutations were present. Two patients are on combined therapy with L-dopa/carbidopa/5-hydroxytryptophan plus BH4, the siblings are on monotherapy with BH4, and the patient with the mild form is now off treatment, presenting with normal plasma phenylalanine levels. CONCLUSION: Long-term follow-up shows that the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency benefits from treatment started in the first months of life and that the phenotype may change with age. Additionally, depending on the type of mutations, prenatal damage to the fetus may multiply the clinical abnormalities and thus worsen the prognosis of the disease. In patients initially diagnosed with the mild peripheral form of the disease, therapy with tetrahydrobiopterin should be stopped after some time to test whether hyperphenylalaninaemia was only a transient condition. SN - 0340-6199 UR - https://wwww.unboundmedicine.com/medline/citation/11388593/Molecular_analysis_and_long_term_follow_up_of_patients_with_different_forms_of_6_pyruvoyl_tetrahydropterin_synthase_deficiency_ L2 - https://dx.doi.org/10.1007/s004310000722 DB - PRIME DP - Unbound Medicine ER -