Primary hyperoxaluria and genetic linkages: an insight into the disease burden from Pakistan

Area of Science:

• Pediatric Nephrology
• Medical Genetics
• Genomic Medicine

Background:

• Autosomal recessive disorders are common in Pakistan, exacerbated by high rates of consanguineous marriage.
• Nephrocalcinosis and nephrolithiasis in children can stem from various genetic conditions, impacting kidney health.
• Understanding the genetic basis of these conditions is crucial for diagnosis and management, especially in developing countries.

Purpose of the Study:

• To determine the prevalence of monogenic causes of nephrocalcinosis and nephrolithiasis in Pakistani children.
• To identify specific genetic mutations responsible for these kidney conditions in the study cohort.
• To assess the clinical and demographic characteristics associated with these genetic disorders.

Main Methods:

• Retrospective analysis of pediatric patients (1-18 years) with nephrocalcinosis from 2010-2019.
• Collection of demographic, clinical, laboratory, and stone analysis data.
• Next-generation sequencing and Sanger sequencing performed on 112 patients to identify genetic mutations.

Main Results:

• Out of 126 children, 87 were diagnosed with primary hyperoxaluria, with specific gene mutations identified.
• Renal tubular acidosis and Bartter's syndrome were diagnosed in 11 and 3 children, respectively.
• Parental consanguinity was reported in 98% of cases; 64% of patients were male, with significant Chronic Kidney Disease progression observed.

Conclusions:

• Monogenic disorders, particularly primary hyperoxaluria, are a significant cause of nephrocalcinosis and nephrolithiasis in Pakistani children.
• The identified mutations appear more severe than those reported in developed nations, indicating a substantial disease burden.
• Limited access to advanced treatments like combined liver-kidney transplantation in Pakistan exacerbates the challenge of managing these severe genetic kidney diseases.