Open AccessMODY5 Hepatocyte Nuclear Factor 1ß (HNF1ß)-Associated Nephropathy: experience from a regional monogenic diabetes referral centre in Singapore
Author(s) -
Chin Tiong Tan,
Su Fen Ang,
Ester Yeoh,
Bing Xing Goh,
Wann Jia Loh,
Cheuk Fan Shum,
M Eng,
Allen Yan Lun Liu,
Lovynn Wan Ting Chan,
Li Xian Goh,
Subramaniam Tavintharan,
Chee Fang Sum,
Su Chi Lim
Publication year - 2022
Publication title -
journal of investigative medicine high impact case reports
Language(s) - English
Resource type - Journals
ISSN - 2324-7096
DOI - 10.1177/23247096211065626
Subject(s) - hnf1b , medicine , maturity onset diabetes of the young , diabetes mellitus , referral , pediatrics , type 2 diabetes , family medicine , endocrinology , genetics , gene , biology , gene expression , homeobox
From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.