Metabolic Serendipities of Expanded Newborn Screening

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Incidental findings on newborn screening (NBS) are secondary results identified during diagnostic workups for targeted conditions.
• These findings may not impact the newborn immediately but can serve as secondary targets for NBS programs.

Purpose of the Study:

• To describe four case reports of incidental findings on NBS that led to the diagnosis of unexpected metabolic diseases.
• To highlight the importance of investigating incidental findings for comprehensive newborn diagnostics.

Main Methods:

• Retrospective analysis of four case reports with incidental findings on NBS.
• Biochemical and genetic evaluations for differential diagnosis of suspected and incidentally found metabolic disorders.

Main Results:

• Case 1: A novel cationic amino acid transporter-2 (CAT-2) defect initially presented as arginase-1 deficiency.
• Case 2: Maternal glutaric aciduria type 1 (GA-1) mimicked carnitine transporter deficiency in the neonate.
• Case 3: Lysinuric protein intolerance (LPI) presented with elevated citrulline levels.
• Case 4: Maternal homocystinuria was diagnosed during vitamin B12 status assessment.

Conclusions:

• Incidental findings on NBS can lead to the diagnosis of various metabolic diseases beyond the initial suspicion.
• These cases underscore the value of thorough investigation of incidental NBS results for accurate diagnosis and management.
• The presented data offer valuable insights for refining differential diagnostic strategies in newborn metabolic screening.