Midd and Melas: A Spectrum of Phenotypes Due to the Same Underlying Mutation

Presentation Number: SAT 616
Date of Presentation: April 1st, 2017

Karina Szczepanczyk*1, Heenam Goel2 and Faryal Sardar Mirza3
1University of CT Health Center, Farmington, CT, 2University of Connecticut School of Medicine, Farmington, CT, 3University of Connecticut Health Center, Farmington, CT

Abstract

Introduction:

Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes caused by m.3243A>G mutation in mitochondrial DNA. This same mutation can cause a more rare but severe syndrome called mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). We describe a case of MIDD with acute mitochondrial decompensation that progressed to MELAS.

Clinical case:

63 year-old male with MIDD (diabetes diagnosed in his 30's, deafness in 40's) and history of hypoglycemic seizures presented for evaluation of altered mental status with fever of 103.3 F, tachycardia 110/min, hypotension (BP 90/60, baseline SBP in 140s) and somnolence. He had pulled out his foley’s the day prior at the rehab facility where he was admitted after a fall induced sacral fracture. History was significant for deafness and cochlear implants. On examination, he had mild proximal muscle wasting but was able to move all extremities. Initial workup was consistent with sepsis and urinary tract infection with leucocytosis. Liver enzymes (LFTs) were normal, lactic acid (9.5 mmol/l (0.5-1.9)) and ammonia were elevated (38 umol/l (11-32)). Valproic acid level was normal.

He was fluid resuscitated and started on broad spectrum antiobiotic followed by Vancomycin for MRSA UTI and bacteremia, and his mentation improved over the next 4 days. On day 5, he became obtunded and a stroke alert was called. CT head was normal, ammonia level had increased (177 umol/L) and LFTs were significantly deranged with AST and ALT of 3141 and 3892 U/L respectively. Lactic acid level was 3.2 mmol/l. Depakote was withheld due to concern about liver toxicity. With underlying mitochondrial disease, valproic acid use and superimposed sepsis, there was a concern for carnitine deficiency causing a catabolic state and inducing hepatic encephalopathy. Carnitine was supplemented pending levels and insulin drip started for better glucose control. He continued to respond poorly and on day 11, he also developed focal left arm paresis. CT head and EEG were negative for stroke and patient was started on levetiracetam. In the prescence of a negative localizing workup, MELAS was a concern, and he was given arginine with subsequent improvement of the focal weakness. The patient continued to gradually improve and was discharged to rehab on Day 19. His hospital course was complicated by atrial fibrillation, heparin-induced thrombocytopenia and DVT in the left leg.

Conclusion:

Maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) are two clinically distinct entities associated with the same mutation in mitochondrial DNA, which may rarely occur in the same patient. We describe a case of MIDD that developed MELAS in the setting of underlying sepsis, which highlights the need to be aware of this rare development, and of its appropriate management.

 

Nothing to Disclose: KS, HG, FSM