RARE CASE OF MITOCHONDRIAL CARDIOMYOPATHY IN ADOLESCENT GIRL

. Предизвикват се


Рядък случай на митохондриална кардиомиопатия с дебют в юношеска възраст
The patient is examined by neurologist due to multisystem character of the disease.Electromyography reveals myopathy.Serum lactate and creatine phosphokinase are elevated.Acute inflammation is excluded with endomyocardial biopsy which also discovers complex III deficiency.Genetic testing identified likely pathogenic mutation in mitochondrial DNA with maternal inheritance.Two years after initial presentation patient was referred for cardiac transplantation due to fast progression of the disease.Mitochondrial cardiomyopathies have variable clinical manifestation which impedes the diagnosis and makes impossible the creation of unified criteria.The disease often affects various organs with high oxygen demand.Multiparametric approach and multidisciplinary team are recommended to increase diagnostic accuracy..

Key words:
mitochondrial disease, mitochondrial cardiomyopathy, cardiomyopathies in adolescents

Introduction
Mitochondrial diseases are heterogenous conditions caused by genetic defects in mitochondrial or nuclear DNA.Cardiac manifestation consists of hypertrophic, dilated, left ventricular non-compaction cardiomyopathy frequently accompanied by rhythm disorders [1].Variable clinical manifestation from no symptoms to severe multi-organ failure impedes the diagnosis [2].

Изводи
Представеният клиничен случай е рядък и до точната диагноза се достигна година след началото на симптоматиката.Необходим бе мултипараметричен и мултидисциплинарен подход в съответствие с последните препоръки на Европейското кардиологично дружество [6].mother being asymptomatic carrier.Genetic testing was performed as part of transplantation program and the exact result is not available.Due to progressive clinical worsening patient underwent successful cardiac transplantation 2 years after the initial presentation.Patient's physical capacity remained mildly reduced during follow up which was probably due to myopathy but no further treatment was required.

Discussion
Mitochondrial cardiomyopathies are rare occurring in 38% of adults and up to 21% of children with mitochondrial disease [3,4].Due to their clinical heterogeneity it is impossible to make unified diagnostic criteria.First manifestation and clinical deteriorations are often linked to metabolic crisis following stress, febrile and infectious illness, surgery.Non-specific changes not associated with single cardiomyopathy and multi-organ involvement can be helpful.Endomyocardial biopsy is often needed for diagnostic confirmation which is а complicated and high risk intervention in pediatric population.Genetic testing of the proband and first degree relatives can also be of guidance minding the fact that most adult gene panels do not include mitochondrial DNA.In our case the lack of symptoms in the mother is interesting and could be explained with heteroplasmy bellow the critical value for phenotypic manifestation inherited as homoplasmy.Recent study using data from whole genome sequencing in clinically unselected populations shows that heteroplasmy leads to variable penetrance and expressivity of mitochondrial gene defects so that the latter could be accidental findings [5].

Conclusion
We present a rare and difficult case which took a year to be diagnosed correctly.Multi-parametric approach and multi-disciplinary team are recommended to increase diagnostic accuracy as stated by European Cardiac Association [6].

Fig. 2 .
Fig. 2. Cardiac MRI examinations five months apart: first study (A and B) and control study (C and D).Dilated left ventricle with diffuse thickening of the myocardium and subepicardial fatty deposit in the mid free wall of the left ventricle (A).Intense late enhancement in virtually all myocardial segments of the left and right ventricles in depth, extending to subepicardial regions along the free wall (B).On the control MRI scan, progression of left ventricular dilatation (C) and the extent and intensity of late enhancement (D) are detected.

Fig. 3 .
Fig. 3. 2D echocardiography.Parasternal long axis view showing dilated, hypertrophied LV with reduced EF (A).Four chamber view and EF measurement with the Simpson method (B).Tissue Doppler of the LV (C).Myocardial strain imaging showing global systolic function impairment with reduced longitudinal strain of all LV segments (D).

Table 1 . Disease Timeline
biopsy: hypertrophy, fibrosis и fibroelastosis.No active inflammation.Complex III deficiency.Genetic testing (nuclear and mitochondrial DNA): likely pathogenic mutation in mitochondrial DNA with maternal inheritance (mother is asymptomatic carrier)