Endocrine Abstracts

JOINT1519

Introduction: MELAS is a rare genetic disorder with multi-system involvement, marked by myopathy, encephalopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA mutations. Mitochondrial disorders are often associated with endocrine abnormalities like diabetes, which results from impaired pancreatic β-cell insulin secretion.

Case Presentation: We present a 63-year-old male diagnosed with MELAS syndrome at the age of 41, following his brother’s diagnosis with encephalopathy and MELAS. He has a significant family history of MELAS. His initial management included Ramipril and Amlodipine for hypertension, along with Co-enzyme Q10 for mitochondrial support. Given the known association of MELAS with diabetes, the patient was referred to endocrinology for an oral glucose tolerance test (OGTT) with showed a fasting glucose of 6.6 mmol/l and a 120-minute level of 17.5 mmol/l, confirming Type 2 diabetes. He was started on repaglinide 500 µg three times daily with meals while avoiding metformin due to the risk of lactic acidosis. During follow-up, his HbA1c was 6.8% (50.8 mmol/mol), and additional testing revealed persistently elevated cholesterol at 10.8 mmol/l, HDL of 1.58 mmol/l, triglycerides of 5.74 mmol/l, and a total cholesterol-to-HDL ratio of 6.8. His creatinine was 124 μmol/l, with an eGFR of 54 mL/min. Despite medication adjustments, his hypertension and diabetes remained sub optimally controlled, necessitating further medications adjustment, His renal function progressively declined, with nephrotic-range proteinuria and creatinine levels rising to 165 μmol/l. Referred to nephrology, he underwent a nephritic workup, renal ultrasound, and biopsy, revealing severe glomerulosclerosis associated with long-term hypertension and diabetes. With CKD progressing to stage 3 (GFR 14 mL/min), he required haemodialysis and, eventually received a left renal transplant. Post-transplant, his glycaemic control became challenging due to persistently elevated glucose levels. He was initiated on Insulatard insulin (18 units in the morning, 16 units in the evening) along with gliclazide 80 mg twice daily. Given the need for frequent glucose monitoring—six times daily—and difficulty using fingerstick testing due to a left-arm fistula, he qualified for the Freestyle Libre continuous glucose monitor. This device significantly improved his quality of life and glycaemic control, with an HbA1c of 55 mmol/mol, glucose levels ranging between 4.9–12 mmol/l, and 63% time-in-range.

Conclusions: This case illustrates the complex challenges of managing diabetes and hypertension in patients with mitochondrial disorders. It emphasizes the importance of early recognition and proactive management of renal and endocrine complications which are essential for improving outcomes.