A Case of Male Siblings with a Mutation in Mitochondrial Gene 3243 tRNA^{Leu (UUR)} Associated with Diabetes and Hypertrophic Cardiomyopathy

Abstract

A 47-year-old man with increasing shortness of breath was admitted to our hospital. Bilateral sensorineural deafness was diagnosed at 21 years of age, and diabetes mellitus was diagnosed at 32 years of age. Proteinuria developd at 38 years of age, and chronic renal failure was diagnosed at 45 years of age. Because of the sensorineural deafness, mitochondrial diabetic and deafness syndrome (MIDD) was suspected. An A to G substitution at nucleotide 3243 in the mitochondrial tRN^{ALeu (UUR)}gene was identified. An echocardiography revealed severe diffuse hypertrophy and asynergy in the left ventricle. Histological examination of the left ventricular wall revealed morphological abnormalities in the mitochondria, leading to a diagnosis of mitochondrial cardiomyopathy. The quadriceps muscle was positive for ragged red fiber, and diffuse cerebral atrophy was detected by brain CT. We then performed ²⁰¹Tl and ¹²³I-BMIPP scintigraphy examinations and discovered a discrepancy, indicating that fatty acid metabolism in the cardiomyocytes had deteriorated but that the perfusion defect was not prominent. These findings were consistent with a diagnosis of mitochondrial cardiomyopathy. The patient's elder brother exhibited a similar clinical phenotype. Sibling cases of mitochondrial cardiomyopathy and diabetes seem to be uncommon.