Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries

Abstract

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\u3eA (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

Still diagnosed too late and under-recognized? A first comprehensive report on primary hyperoxaluria from Poland

“…The paucity of published data on PH1 cases from this region may indirectly support this hypothesis. Other reasons contributing to the lower real world data on PH1 prevalence in Poland may be related to the rarity of consanguineous marriages and historically little emigration from regions with a higher burden of the disease, like North Africa or Pakistan [4,29,30].…”

“…Similarly to PH1, the excess of oxalate is derived from glyoxylate and in addition, the deficiency of GRHPR leads to conversion of hydroxypyruvate to L-glycerate [2]. PH2 accounts for approximately 9% of the PH cases identified in Europe, but is more prevalent in Asian populations [3,4]. PH type 3 (PH3; MIM #613616) is associated with loss of the HOGA1 gene function.…”

Combined liver‐kidney transplantation for primary hyperoxaluria type I in children: Single Center Experience

“…Early diagnosis and aggressive conservative management are reported to delay ESKD and provide the children with better quality of life. Conservative management needs strict follow‐up, where the child should be hyperhydrated, receive citrate as a calcium oxalate crystallization inhibitor and pyridoxine whenever responsive.…”

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up

“…Both PH2 and PH3 are deemed to be extremely rare, although recent evidence suggests that PH3, and to a lesser degree PH2, may in fact be underdiagnosed, particularly in regions where kidney stones are endemic. 1,3 PH2 is caused by a deficiency of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GR/HPR) 4,5 encoded by GRHPR. 6 GR/HPR enzyme activity is highest in the liver but also is demonstrated in leukocytes and the kidney.…”