BH₄ deficiency identified in a neonatal screening program for hyperphenylalaninemia

Area of Science:

• Biochemistry
• Genetics
• Neonatal Medicine

Background:

• Tetrahydrobiopterin (BH4) deficiencies are inborn errors of metabolism.
• These deficiencies cause hyperphenylalaninemia and severe neurological impairment if untreated.
• Neonatal screening programs are crucial for early diagnosis.

Purpose of the Study:

• To determine the prevalence and characteristics of BH4 deficiencies in Minas Gerais.
• To evaluate the impact of early diagnosis via neonatal screening on patient outcomes.

Main Methods:

• Descriptive study of BH4-deficient patients identified through the Minas Gerais Neonatal Screening Program.
• Analysis of patient data including diagnosis, clinical presentation, and treatment response.

Main Results:

• Prevalence of BH4 deficiency was 2.1 per 1,000,000 live births.
• Common deficiencies included 6-pyruvoyl-tetrahydropterin synthase, GTP cyclohydrolase I, and dihydropteridine reductase.
• Neonatally screened patients showed significantly better neuropsychomotor development after early treatment compared to those diagnosed later.

Conclusions:

• BH4 deficiency prevalence in Minas Gerais is slightly higher than reported globally.
• Early treatment initiation (before 5 months) is critical for preventing intellectual disability.
• Screening for BH4 deficiencies in newborns with hyperphenylalaninemia is strongly recommended.