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Guanosine triphosphate cyclohydrolase I deficiency: early diagnosis by routine urine pteridine screening
Insights
Early screening for guanosine triphosphate cyclohydrolase I deficiency in infants with hyperphenylalaninemia is crucial. This genetic disorder can be detected before symptoms appear, enabling timely dietary intervention.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Newborn screening programs often identify hyperphenylalaninemia, typically managed as phenylketonuria.
- Guanosine triphosphate cyclohydrolase I (GTPCH I) deficiency is a rare genetic cause of hyperphenylalaninemia, affecting tetrahydrobiopterin synthesis.
Observation:
- A 4-month-old infant with elevated serum phenylalanine underwent diagnosis for phenylketonuria.
- Subsequent urinary pteridine analysis revealed critically low neopterin and biopterin levels.
- This finding prompted further investigation into cofactor variant disorders.
Findings:
- Confirmatory assays, including pteridine profiling and liver biopsy, confirmed GTPCH I deficiency.
- The diagnosis was established before the manifestation of significant clinical symptoms.
- Tetrahydrobiopterin-loading studies supported the diagnosis.
Implications:
- Highlights the importance of routine cofactor variant screening in infants diagnosed with hyperphenylalaninemia.
- Early detection of GTPCH I deficiency allows for prompt initiation of dietary therapy.
- Prevents severe neurological complications associated with untreated tetrahydrobiopterin deficiencies.
Abstract:
A deficiency of hepatic guanosine triphosphate cyclohydrolase I is reported in a 4-month-old infant in whom positive results on a Guthrie phenylketonuria test in the neonatal period were found. Because of the significantly elevated serum phenylalanine levels a diagnosis of classical phenylketonuria was made, and dietary therapy was started. Urinary pteridine screening for cofactor variants, however, revealed extremely low levels of both neopterin and biopterin. This suggested the possibility of guanosine triphosphate cyclohydrolase I deficiency and led to additional confirmatory assays. Repeat urine, serum, and CSF pteridine profiles, combined with tetrahydrobiopterin-loading studies and the assay of guanosine triphosphate cyclohydrolase I activity in a liver biopsy, confirmed the defect. It is significant to note that the diagnosis was made before the onset of major clinical symptoms. This case illustrates the need for routine cofactor variant screening of all infants in whom hyperphenylalaninemia is diagnosed in the neonatal period.