Clinical characteristics, genetic profile and short-term outcomes of children with primary hyperoxaluria type 2 : a nationwide experience
© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Pediatric nephrology (Berlin, Germany) - 39(2024), 4 vom: 02. Feb., Seite 1093-1104 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Krishnasamy, Sudarsan [VerfasserIn] |
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| Links: |
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| Themen: |
C.494 g > a |
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| Anmerkungen: |
Date Completed 28.02.2024 Date Revised 28.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00467-023-06200-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364068582 |
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| 100 | 1 | |a Krishnasamy, Sudarsan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical characteristics, genetic profile and short-term outcomes of children with primary hyperoxaluria type 2 |b a nationwide experience |
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| 500 | |a Date Revised 28.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Review | |
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| 650 | 4 | |a Nephrocalcinosis | |
| 650 | 4 | |a Nephrolithiasis | |
| 650 | 4 | |a Primary hyperoxaluria type 2 | |
| 650 | 4 | |a c.494 g > a | |
| 650 | 4 | |a c.735-1G > A | |
| 700 | 1 | |a Deepthi, Bobbity |e verfasserin |4 aut | |
| 700 | 1 | |a Kamath, Nivedita |e verfasserin |4 aut | |
| 700 | 1 | |a Iyengar, Arpana |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Christy Cathreen |e verfasserin |4 aut | |
| 700 | 1 | |a Uthup, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Saha, Anshuman |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Georgie |e verfasserin |4 aut | |
| 700 | 1 | |a Agarwal, Indira |e verfasserin |4 aut | |
| 700 | 1 | |a Tiewsoh, Karalanglin |e verfasserin |4 aut | |
| 700 | 1 | |a Bhat, Nowneet Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Mandal, Kausik |e verfasserin |4 aut | |
| 700 | 1 | |a Krishnamurthy, Sriram |e verfasserin |4 aut | |
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