Myocardial Dysfunction in Maternally Inherited Diabetes and Deafness

The pattern and degree of myocardial involvement in maternally inherited diabetes and deafness (MIDD) is unclear (1–3). A recent French multicenter study that examined 54 patients with MIDD described left ventricular hypertrophy (LVH) in 8 and congestive heart failure (CHF) in 2 patients (2). Here, we reported a patient with mtDNA 3243 mutation who developed the full clinical, echocardiographic, and radiologic picture of CHF.

A 54-year-old man with diabetes since age 23 years was diagnosed as having MIDD based on the findings of deafness, familial history of diabetes, and short stature involving his younger brother and mother. His older brother also presented diabetes but not short stature or deafness. Insulin was started when the patient was age 38 years, and he never presented ketosis. On physical examination, blood pressure was normal. Right hemiparesy was present as sequelae of a previous cerebrovascular accident. Autonomic and peripheral neuropathy were detected. Fundoscopy disclosed nonproliferative diabetic retinopathy. Laboratorial evaluation included a glucagon test that displayed decreased pancreatic insulin secretion (baseline and 6-min C-peptide values of 1.2 and 1.3 ng/ml, respectively). Urinary albumin excretion was 1,112 mg/24 h, and serum creatinine was 1.6 mg/dl. The younger brother and mother, but not the older brother, also presented macroalbuminuria. The analysis of mitochondrial DNA obtained from peripheral leukocytes revealed an A→G mutation at position 3243 in the patient and in his mother. The older and younger brother were not affected. Cerebral MRI revealed multiple hyperintense areas in cortex, globus pallidus, and cortical atrophy. Blood lactate concentration was 1.45 mmol/l at baseline (n = 0.3–1.3 mmol/l) and increased to 2.26 mmol/l after a carbohydrate-rich meal. Thyroid hormone concentrations were T4 = 2.6 μg/dl (normal range 4.5–12.5 μg/dl), thyroid-stimulating hormone = 16.4 μUI/ml (upper limit 4.5 μUI/ml). Anti-thyroperoxidase was normal, and oral thyroxine was started. An echocardiogram was performed and revealed a diffuse pattern of birefringence, which is suggestive of myocardial infiltration with an ejection fraction of 54% and LVH. The blood cell count found 20,000 leukocytes, with 34% of eosinophils. The patient’s records confirmed eosinophilia (exceeding 1,500/μl) in the previous 6 months, which persisted after antiparasitic treatment. The presumptive diagnosis of eosinophilic myocardial dysfunction was assumed and prednisone therapy (60 mg/day) was started.

The patient visited the emergency unit 4 months later presenting resting dyspnea and pronounced bilateral lower-limb edema. A chest X-ray revealed the presence of pulmonary effusion. The electrocardiogram showed possible lateral ischemia and atrial enlargement. The echocardiogram disclosed a small pericardial effusion, a diffuse birefringence pattern, and an ejection fraction of 41%, suggesting myocardiopathy. Cardiac catheterization was performed and revealed a 50% segmental lesion on the anterior descendent artery. A myocardial biopsy was indicated and demonstrated muscle fiber hypertrophy and degenerative changes, features consistent with the presence of dilated cardiomyopathy, eliminating the diagnosis of eosinophilic myocardiopathy.

Previous cases of cardiac dysfunction in mitochondrial diabetes have been described (2–4). A Japanese group showed the fast progressive nature of cardiac involvement in a diabetic patient who developed mitochondrial cardiomyopathy, with diffuse left ventricle hypokinesis. The endomyocardial biopsy described mild hypertrophy and myofibrils disarrangement with vacuolar degeneration, a pattern similar to our findings. Accordingly, our patient also presented a fast progression to heart failure, with deterioration of cardiac function over a period of 4 months. Momiyama et al. (5) studied 12 diabetic patients with mtDNA 3243 mutation and pointed out that they have a significantly higher proportion of LVH as compared with ordinary diabetic patients (33 vs. 7%). We believe that the present report contributes to characterize the myocardial involvement in the mitochondrial syndrome, providing clues to understanding the related disease mechanisms.