Clinical, biochemical, and radiologic profiles of Filipino patients with 6-Pyruvoyl-Tetrahydrobiopterin Synthase (6-PTPS) deficiency and their neurodevelopmental outcomes
https://doi.org/10.47895/amp.vi0.9439
- Author:
Leniza G. de Castro-Hamoy
1
,
2
,
3
;
Ma. Anna Lourdes A. Moral
1
;
Loudella V. Calotes-Castillo
1
;
1Mary Ann R. Abacan
1
,
2
;
Cynthia P. Cordero
4
;
Maria Lourdes C. Pagaspas
1
,
5
;
Ebner Bon G. Maceda
1
,
2
;
Sylvia C. Estrada
1
,
2
;
Mary Anne D. Chiong
1
,
6
Author Information
1. Department of Pediatrics, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines
2. Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Manila, Philippines
3. The Royal Childrens Hospital, Melbourne, VIC, Australia
4. Department of Clinical Epidemiology, College of Medicine, University of the Philippines Manila, Manila, Philippines
5. Department of Pediatrics, Manilamed-Medical Center Manila, Manila, Philippines
6. Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines
- Publication Type:Journal Article
- Keywords:
6-PTPS deficiency;
Hyperphenylalaninemia;
Tetrahydrobiopterin
- From:
Acta Medica Philippina
2024;58(Early Access 2024):1-6
- CountryPhilippines
- Language:English
-
Abstract:
Background:Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia.
Objective:This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team.
Methods:The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described.
Results:Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder.
Conclusion:Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.
- Full text:9439-Other-154975-1-10-20240424.pdf
