Propionic acidemia in Mexico: Clinical and genotypic spectrum.

Area of Science:

• Genetics
• Metabolic Disorders
• Pediatrics

Background:

• Propionic acidemia (PA) is a metabolic disorder caused by propionyl-CoA carboxylase deficiency, affecting PCCA and PCCB genes.
• Limited data exists on PA's clinical and genotypic spectrum in Mexico.
• PA is not part of the mandatory Mexican newborn screening (NBS) program.

Purpose of the Study:

• To characterize the clinical and genotypic spectrum of PA in Mexican patients.
• To evaluate the potential inclusion of PA in the Mexican NBS program.

Main Methods:

• Retrospective analysis of 51 Mexican PA patients.
• Clinical data collection including symptom onset, diagnosis, and outcomes.
• Next-generation sequencing (NGS) for PCCA and PCCB gene analysis.
• In silico protein modeling for novel variants.

Main Results:

• Most patients (92.1%) had early symptom onset (mean 21 days) and delayed diagnosis (mean 5.1 months).
• High early mortality rate (66.7%) and significant neurological impairment (60%) were observed.
• NGS identified PCCA-related (46.66%) and PCCB-related (53.3%) cases, including four novel PCCA variants and one novel PCCB variant.

Conclusions:

• PA presents severely in Mexico with high mortality and neurological sequelae.
• PA warrants inclusion in the Mexican NBS program for early detection and management.
• Increased pediatrician awareness of PA clinical signs is crucial for timely diagnosis and intervention.