Molecular Diagnosis of Primary Hyperoxaluria Type 1 and Distal Renal Tubular Acidosis in Moroccan Patients With Nephrolithiasis and/or Nephrocalcinosis.

Abstract

Nephrolithiasis (NL) and urolithiasis (UL) are usual reasons for hospitalization and presentation in pediatric outpatient departments and their incidence continues to rise worldwide. In Morocco, a previous epidemiological study done in the Fez region between January 2003 and November 2013 reported a prevalence of 0.83% of childhood UL. In two studies, heritability accounted for almost half of all NL or nephrocalcinosis (NC) prevalence. Genetic factors must be considered in the etiological diagnosis of urinary lithiasis in Morocco since the frequency of consanguineous marriages is high. Hereditary tubular disorders, especially distal renal tubular acidosis (dRTA) and Dent disease, and metabolic disorders like idiopathic hypercalciuria and hyperoxaluria are the most common causes of medullary NC. Primary hyperoxaluria type 1 (PH1), which can generate an early onset of NC, and often chronic kidney disease (CKD) should always be considered and thoroughly diagnosed. The aim of this work was to establish a molecular diagnosis of PH1 and dRTA and, thus, to predict and explain the disease phenotype in a cohort of 44 Moroccan patients with NL and/or NC by analyzing the AGXT and ATP6V1B1 genes that cause NL and/or NC when mutated. Disease phenotype was molecularly explained and solved in six of 44 individuals with NL and/or NC (13.6%). In the pediatric subgroup of individuals, a causative mutation in 16.2% was identified, whereas in the adult cohort no pathogenic mutation was detected. In our patients, PH1 was objectified in 67% of cases followed by dRTA in 33% of cases. We suggest that prompt detection and prophylactic treatment of UL are necessary to limit the risk of everlasting renal damage and thus prevent or delay the progression to CKD.