Identification of a mitochondrial gene mutation in a systemic disease manifesting primarily as hypertrophic cardiomyopathy
█ Case report
Tringer Annamária1, Grosz Zoltán2, Nagy Viktória1, Gál Anikó2, Csányi Beáta1, Lidia Hategan1, Borbás János1, Gavallér Henriette1, Pálinkás Eszter1, Forster Tamás1, Molnár Mária Judit2, Sepp Róbert1
1Szegedi Tudományegyetem, II. sz. Belgyógyászati Klinika és Kardiológiai Központ, Szeged
2Semmelweis Egyetem, Genomikai Medicina és Ritka Betegségek Intézete, Budapest
Mitochondrial diseases belong to a heterogeneous group of multisystem diseases as rare systemic disorders caused by mutations of the mitochondrial genome (mtDNA) and cc. 1500 nuclear genes which are responsible for the mitochondrial function. The disease primarily affects organs with high energy expenditure as the central nervous system and skeletal muscle, but numerous other forms are known, in which disease-specific symptoms may be present. The disease typically shows maternal inheritance. In our study genetic analysis was performed in a patient presenting with the cardiac phenotype of hypertrophic cardiomyopathy.
A 32-years-old female patient, with short stature (140 cm), came to medical attention at the age of 27 when she presented with exertional dyspnea and chest discomfort. Hearing disorder was known for years, which was attributed to bilateral cochlear lesion. ECG showed short PQ interval and signs of left ventricular hypertrophy. Echocardiographic and MRI examinations confirmed non-obstructive hypertrophic cardiomyopathy, enlarged left atrium, severe concentric left (LVmax: 15 mm) and right ventricular hypertrophy (RVmax: 8 mm). During the course of the disease type I diabetes mellitus developed and then visual disturbances appeared, due to a confirmed retinal dystrophy. Her laboratory findings showed elevated LDH, CK, troponin T, and NTproBNP values. Neurological status was negative. Her brother was known to have stroke, epilepsy, septal hypertrophy, hyperhomocysteinaemia, and he died at age of 17 due to recurrent strokes. Her mother has been known for having hearing disorder and diabetes mellitus.
Genetic screening for sarcomere gene mutations and Fabry disease causing mutations for the GLA gene was negative. Analysis of the mitochondrial genome confirmed a m.3243A>G mutation, most commonly found in MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) syndrome.
Our case points out to a possible mitochondrial disease and the need for genetic testing in cases of hypertrophic cardiomyopathy with systemic involvement.