Arginase 1 Deficiency: using genetic databases as a tool to establish global prevalence

Area of Science:

• Genetics
• Metabolic Disorders
• Epidemiology

Background:

• Arginase 1 Deficiency (ARG1-D) is a rare, severe inherited metabolic disease.
• Limited newborn screening and diagnostic challenges lead to scarce prevalence data.
• Previous US birth prevalence estimates were 1.1 cases per million live births.

Purpose of the Study:

• To estimate the global birth prevalence of Arginase 1 Deficiency (ARG1-D).
• To utilize genetic population databases for a more accurate prevalence assessment.
• To compare genetic database-derived prevalence with existing newborn screening data.

Main Methods:

• Systematic search of MEDLINE and EMBASE for ARG1-D variants.
• Annotation of variants with allele frequencies from gnomAD.
• Calculation of ethnicity-specific prevalence using Hardy-Weinberg equation and consanguinity rates for 38 countries.

Main Results:

• Global birth prevalence of ARG1-D estimated at 2.8 cases per million live births.
• Country-specific estimates ranged from 0.92 to 17.5 cases per million.
• Population prevalence estimated at 1.4 cases per million people (1/726,000).

Conclusions:

• Genetic database analysis suggests ARG1-D is more frequent than previously indicated by newborn screening.
• Higher confidence in estimates for North America and Europe due to data availability.
• Emphasizes the need for increased disease education, testing, and standardized screening for ARG1-D.