Clinical, Biochemical, and Radiologic Profiles of Filipino Patients with 6-Pyruvoyl-Tetrahydrobiopterin Synthase
Leniza G de Castro-Hamoy1,2,3, Ma Anna Lourdes A Moral1, Loudella V Calotes-Castillo1
1Department of Pediatrics, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.
Insights
Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is a metabolic disorder causing hyperphenylalaninemia. Despite early newborn screening and treatment, neurodevelopmental outcomes for affected children remain unsatisfactory.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder.
- It leads to tetrahydrobiopterin (BH4) deficiency, resulting in hyperphenylalaninemia.
Purpose of the Study:
- To describe the clinical, biochemical, radiologic, and neurodevelopmental profiles of patients with 6-PTPS deficiency.
- To evaluate outcomes in patients diagnosed via newborn screening and confirmed through specific tests.
Main Methods:
- A single-center descriptive case series study.
- Involved nine patients aged 1 year 2 months to 14 years 5 months.
- Data collected included clinical, biochemical, radiologic profiles, and neurodevelopmental evaluations.
Main Results:
- Common clinical manifestations included hypotonia, poor suck, and seizures, with seizures persisting post-treatment.
- Phenylalanine levels significantly decreased after treatment initiation.
- Eight of nine patients exhibited developmental delay or intellectual disability; two had posterior lobe brain atrophy.
Conclusions:
- Newborn screening is vital for early identification and management of 6-PTPS deficiency.
- Diagnostic confirmation via DHPR activity, urine pterins, or molecular analysis is crucial.
- Despite early treatment, neurodevelopmental outcomes in 6-PTPS deficiency patients are often unsatisfactory.
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.
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