Clinical characteristics, genetic profile and short-term outcomes of children with primary hyperoxaluria type 2: a nationwide experience.

Publisher: Springer International Country of Publication: Germany NLM ID: 8708728 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-198X (Electronic) Linking ISSN: 0931041X NLM ISO Abbreviation: Pediatr Nephrol Subsets: MEDLINE

Publication: Berlin : Springer International
Original Publication: Berlin : Springer International, c1987-

Hyperoxaluria, Primary*/complications ; Hyperoxaluria, Primary*/diagnosis ; Hyperoxaluria, Primary*/genetics ; Nephrolithiasis*/genetics ; Renal Insufficiency, Chronic*; Child ; Humans ; Infant ; Genetic Profile

Background: Three types of primary hyperoxaluria (PH) are recognized. However, data on PH type 2 (PH2), caused by defects in the GRHPR gene, are limited.
Methods: We reviewed the medical records of patients < 18 years of age with genetically-proven PH2 from seven centres across India to identify the age of onset, patterns of clinical presentation, short-term outcomes and genetic profile, and to determine if genotype-phenotype correlation exists.
Results: We report 20 patients (all with nephrolithiasis or nephrocalcinosis) diagnosed to have PH2 at a median (IQR) age of 21.5 (7, 60) months. Consanguinity and family history of kidney stones were elicited in nine (45%) and eight (40%) patients, respectively. The median (IQR) serum creatinine at PH2 diagnosis was 0.45 (0.29, 0.56) mg/dL with the corresponding estimated glomerular filtration rate being 83 (60, 96) mL/1.73 m ² /min. A mutational hotspot (c.494 G > A), rare in Caucasians, was identified in 12 (60%) patients. An intronic splice site variant (c.735-1G > A) was noted in five (25%) patients. Four (20%) patients required surgical intervention for stone removal. Major adverse kidney events (mortality or chronic kidney disease (CKD) stages 3-5) were noted in six (30%) patients at a median (IQR) follow-up of 12 (6, 27) months. Risk factors for CKD progression and genotype-phenotype correlation could not be established.
Conclusions: PH2 should no longer be considered an innocuous disease, but rather a potentially aggressive disease with early age of presentation, and possible rapid progression to CKD stages 3-5 in childhood in some patients. A mutational hotspot (c.494 G > A variant) was identified in 60% of cases, but needs further exploration to decipher the genotype-phenotype correlation.
(© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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BT/PR25805/MED/12/771/2017 Department of Biotechnology (DBT), Government of India

Keywords: GRHPR; Nephrocalcinosis; Nephrolithiasis; Primary hyperoxaluria type 2; c.494 g > a; c.735-1G > A

Primary hyperoxaluria type 2

Date Created: 20231102 Date Completed: 20240228 Latest Revision: 20240228

20240228

10.1007/s00467-023-06200-9

37914965