Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries
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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.
KeywordsPrimary hyperoxaluria Consanguinity Oxalate stones Oxalosis End-stage renal disease Pakistan origin Oxalate crystals Mutation analysis
We acknowledge the support and valued critique of earlier drafts of this paper by Professor Dawn S Milliner, Director, Rare Kidney Stone Consortium, and principal investigator, Primary Hyperoxaluria group, Mayo Clinic Hyperoxaluria Center, Rochester. We acknowledge with gratitude the contribution of data from the OxalEurope registry (see http://www.oxaleurope.com) and the sharing of laboratory data by Farooq Ghani, M.B.B.S., M.S., Ph.D., FACB, Diplomate American Board, Service Chief & Director Clinical Laboratories, Associate Professor, Department of Pathology, Aga Khan University.
Compliance with ethical standards
Conflict of interest
All authors have declared that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
This study has not received any grant funding.
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