Rare MODY subtypes frequently misdiagnosed

2019-01-21T10:25:32+00:00December 31st, 2018|News report, Paediatric endocrinology|

medwireNews: Rare forms of maturity onset diabetes of the young (MODY) are frequently misdiagnosed as type 1 or even type 2 diabetes, say researchers, despite patients presenting with distinct characteristics.

Katharina Warncke (Technische Universität München, Germany) and co-researchers found that 38% of patients were initially misdiagnosed, even with diagnosis presumably being aided in some cases by a history of MODY in other family members.

The team obtained data on 929 patients under the age of 20 years with a confirmed MODY diagnosis, representing 1.2% of all patients in the DPV Diabetes Registry. The majority of these had GCK-MODY (n=609) or HNF1A-MODY (n=230), but for this analysis the researchers focused on patients with the much rarer HNF4A and HNF1B mutations, comprising 44 and 35 individuals, respectively.

Given the rarity of these conditions, “this represents a large number of cases allowing a comprehensive characterization with a focus on clinical data, treatment and metabolic control”, they write in The Journal of Clinical Endocrinology & Metabolism.

Three-quarters of patients with HNF4A-MODY were classified as having MODY from the time of diabetes diagnosis, but eight were reclassified from an initial diagnosis of type 1 diabetes and three from a type 2 diabetes diagnosis, after an average of 1.3 years.

Fewer (45.7%) patients with HNF1B-MODY had a correct diagnosis from the outset, with 14 initially diagnosed with type 1 diabetes and five with type 2 diabetes and reclassification occurring after an average of 1.6 years.

The researchers stress that the proportions of initial type 1 and type 2 diagnoses do not reflect the actual prevalence rates in this young age group. They say that this highlights the need to revalidate clinical diagnoses of paediatric type 2 diabetes over time, as it is statistically more likely to be MODY.

At the time of diagnosis, MODY patients were older, on average, than type 1 diabetes patients, at 13.8 and 13.5 years for those with the HNF4A and HNF1B mutations, respectively, compared with 8.8 years. Also, glycated haemoglobin levels were significantly lower, at 6.9% (51.9 mmol/mol) in HNF4A-MODY patients and 7.0% (53.0 mmol/mol) in HNF1B-MODY patients, compared with 9.5% (80.33 mmol/mol) in those with type 1 diabetes.

Average C-peptide levels were 0.9 ng/mL in patients with type 1 diabetes; these were significantly higher in those with HNF4A-MODY, at 1.8 ng/mL, and nonsignificantly higher in those with HNF1B-MODY, at 1.5 ng/mL.

An additional characteristic of the HNF4A-MODY patients was that boys had a significantly reduced height standard deviation score of –0.9.

“This finding supports the hypothesis that HNF4A mediates the sex-dependent effect of growth hormone on liver gene expression, which may have an effect on height”, say the researchers.

At diagnosis, 48.1% of HNF4A-MODY patients and 71.4% of HNF1B-MODY patients were put on insulin. This had reduced by the most recent visit, in line with the reclassification of patients to a MODY diagnosis, but only to a respective 36.4% and 65.7%.

“The high proportion of patients on insulin therapy might reflect the fact that some diabetologists may not be aware of the possibility to treat patients with HNF4A-MODY with [oral antidiabetics]/lifestyle therapy, maybe due to the rarity of this disease”, say Warncke and team.

By Eleanor McDermid

J Clinical Endocrinol Metab 2018; doi:10.1210/jc.2018-01696

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