Primary hyperoxalurias (PH) are devastating, autosomal recessive diseases causing renal stones. Undifferentiated hyperoxaluria is seen in up to 43% of Pakistani paediatric stone patients. High rates of consanguinity in Pakistan suggest significant local prevalence. There is no detailed information regarding number of cases, clinical features, and genetics in Pakistan-origin (P-o) patients. We reviewed available information on P-o PH patients recorded in the literature as well as from two major PH registries (the Rare Kidney Stone Consortium PH Registry (RKSCPHR) and the OxalEurope PH Registry (OxER); and the Aga Khan University Hospital in Pakistan. After excluding overlaps, we noted 217 P-o PH subjects (42 in OxER and 4 in RKSCPHR). Presentations were protean. Details of mutations were available for 94 patients of 201 who had genetic analyses. Unique mutations were noted. Mutation [c.508G>A (p. Gly170Arg)] (present in up to 25% in the West) was reported in only one case. In one series, only 30% had mutations on exons 1,4,7 of AGXT. Of 42 P-o patients in OxER, 52.4% were PH1, 45.2% PH2, and 2.4% PH3. Of concern is that diagnosis was made after renal transplant rejection (four cases) and on bone-marrow aspiration (in five). Lack of consideration of PH as a diagnosis, late diagnosis, and loss of transplanted kidneys mandates that PH be searched for diligently. Mutation analysis will need to extend to all exons and include PH 1,2,3. There is a need to spread awareness and identify patients through a scoring or screening system that alerts physicians to consider a diagnosis of PH.
Keywords: Consanguinity; End-stage renal disease; Mutation analysis; Oxalate crystals; Oxalate stones; Oxalosis; Pakistan origin; Primary hyperoxaluria.