MON-057 MODY diagnosis: Missed opportunity to avert insulin therapy. A case series
Paediatrics and Child Health
Background: Prevalence of MODY is 1.2% in pediatric diabetes population. SEARCH study reported most of these patients were misdiagnosed as T1DM or T2DM up to 36% and 51% respectively (1). GCK (MODY 2) and HNF1A/HNF4A (MODY3) are the most common forms of MODY. Despite improvement in testing strategy (panel testing instead of step-wise approach) and cost, MODY testing remains underutilized. These conditions do not require insulin therapy, and MODY 2 patients may even be discharged from clinic after diagnosis. We present 4 cases and valuable lessons learned.
MODY 2 Case 1. 4 yo M referred for hyperglycemia in the 300s during surgery. A1c 6.4%. FBG at home 150s, asymptomatic. MGM and MGM’s siblings have diabetes. Diabetes autoantibodies (DAA) negative. C-peptide 5.4 (NL 0.78 - 5.19 ng/ml). MODY panel (GeneDx) showed heterozygous mutation in GCK gene (c.70 C>T). Patient remains off insulin, family reassured and advised to undergo genetic testing.
MODY 2 Case 2. 8 yo M diagnosed at local ED with “T1DM” after presenting with polyuria, polydipsia, and random BG 237. A1c 6.7%, C-peptide 1.9, started on basal-bolus insulin. MODY panel (sent a year later when patient was found to have low insulin requirement, negative DAA) showed pathogenic variant in GCK gene. Weaned from insulin, A1c unchanged (6.3–7%). Mother found to have same mutation. MODY 3 Case 1. 16 yo F referred by PCP who started her on insulin a year prior after an incidental finding of hyperglycemia. A1c was 7.5% at diagnosis. Mom, MGM have diabetes, unknown type (MGM thin by report). DAA neg, C-Peptide 1.74. MODY Panel showed HNF1A heterozygous gene mutation for RI31Q. She was switched to Glyburide, blood glucose 90s. MODY 3 Case 2. 10 yo M referred from the ED for “T1DM” (weight loss, fatigue, A1c 7.6%) started on basal-bolus insulin, but lost to follow up for a year. Brother has MODY 3. DAA neg, C-Peptide 3.1. Targeted gene sequencing showed HNF1A gene mutation. He was switched to Glyburide, A1c improved to 6.7%. However, patient became noncompliant as teenager, A1c now 9.3%.
Conclusion: MODY remains underdiagnosed. A high index of suspicion should be maintained in nonobese, DAA-negative patients diagnosed with DM before 25yo. Although DAA and genetic testing can be costly, diagnosis can dramatically alter diabetes management as illustrated in all 4 cases, and overall cost of management may be lower in the end. Patients with MODY 2 do not develop vascular complications associated with diabetes, nor require pharmacotherapy. MODY 3 patients may be safely switched to sulfonylurea monotherapy, though degree of diabetes control depends on compliance with medication. Testing gives relatives previously misdiagnosed the opportunity to improve their own quality of life. More education for health care providers is warranted for prompt diagnosis and appropriate management of this condition.
Journal of the Endocrine Society
Matlock, K. A.,
Bowlby, D. A.,
(2020). MON-057 MODY diagnosis: Missed opportunity to avert insulin therapy. A case series. Journal of the Endocrine Society, 4(Supplement_1), A115-A116.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_women_childhealth_paediatr/1308