Effective Newborn Screening for Type 1 and 3 Primary Hyperoxaluria

Area of Science:

• Genetics
• Metabolic Disorders
• Neonatal Screening

Background:

• Newborn screening (NBS) programs are successful but limited in scope.
• Genomic NBS offers expanded detection of treatable genetic disorders.
• Primary hyperoxalurias (PH1-3) are rare, severe autosomal recessive diseases requiring early diagnosis.

Purpose of the Study:

• To evaluate the feasibility of genomic NBS for primary hyperoxalurias (PH1-3).
• To screen newborns for prevalent PH genetic variants.
• To identify carriers and affected infants for timely intervention.

Main Methods:

• Prospective pilot study integrated into the German NBS program.
• Multiplex PCR screening of DNA from dried blood spots for key PH1 and PH3 variants.
• Follow-up urine analysis and Sanger sequencing for identified carriers.

Main Results:

• Screened 77,199 newborns for PH1 and PH3 variants.
• Identified 274 potential carriers for AGXT (PH1) and 287 for HOGA1 (PH3).
• Detected two symptomatic compound heterozygous infants (one PH1, one PH3) and one additional symptomatic PH1 patient through family history.

Conclusions:

• Genomic NBS is effective for detecting primary hyperoxalurias, even in smaller populations.
• This approach enables early identification of at-risk infants.
• Genomic screening holds promise for expanding NBS capabilities for rare genetic diseases.