We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Clinical characteristics, genetic profile and short-term outcomes of children with primary hyperoxaluria type 2: a nationwide experience.
- Authors
Krishnasamy, Sudarsan; Deepthi, Bobbity; Kamath, Nivedita; Iyengar, Arpana; Thomas, Christy Cathreen; Uthup, Susan; Saha, Anshuman; Mathew, Georgie; Agarwal, Indira; Tiewsoh, Karalanglin; Bhat, Nowneet Kumar; Mandal, Kausik; Krishnamurthy, Sriram
- Abstract
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 m2/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.
- Subjects
INDIA; EVALUATION of medical care; STATISTICS; STATISTICAL significance; PEDIATRICS; REGRESSION analysis; INBORN errors of carbohydrate metabolism; SYMPTOMS; KAPLAN-Meier estimator; GENOTYPES; DESCRIPTIVE statistics; RESEARCH funding; DATA analysis software; GENETIC profile; PHENOTYPES
- Publication
Pediatric Nephrology, 2024, Vol 39, Issue 4, p1093
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-023-06200-9