Heart-transplantation in a patient with pathogenic saromere
and α galactosidase A mutation: a case report.
2Semmelweis University, Pediatric Center, Hungary
3Semmelweis University, Department of Cardiology, Hungary
4Semmelweis University, Department of Pathology and Experimental Cancer Research, Hungary
Background: Titin is a key component of the sarcomere. Mutations in the TTN gene encoding titin are the most common genetic cause of DCM. Fabry disease is a rare X linked lysosomal storage disease, caused by mutations in the GLA gene encoding α galactosidase A (AGAL). Reduced enzymatic activity of AGAL results in accumulation of glycosphingolipids in multiple cell types. Cardiac involvement may present with left ventricular hypertrophy.
Case summary: We report a case of an 18-year-old male patient, who was referred to our centre with Fabry disease. At the age of 16 he presented with signs of heart failure. Cardiac MRI showed severe dilated cardiomyopathy. Due to rapid progression of severe heart failure he underwent a succesful heart transplantation. A genetic panel for DCM was performed. Mutations of TTN (c. 7399_7390) and GLA (c.773G>A ) were identified. The AGAL activity was decreased (0,7 mmol/l/h), and the lyso Gb3 level was elevated (6,7 ng/ml). The histological analysis of the explanted heart did not show any sign of storage disease. Clinical signs of other possible manifestations of Fabry disease were absent. The segregation analysis revealed the same GLA mutation in the proband’s mother, who has been treated for DCM. The patient attends regular cardiology appointments and is asymptomatic.
Discussion: Genetic counseling categorised both the TTN and GLA mutations pathogenic. The GLA variant is described as a „late onset” variant in the literature. In the clinical geneticist’s opinion both mutations may have contributed to the clinical picture, therefore the cause of the severe heart failure may have been the TTN mutation, but we should look out for later onset cardiac involvement of Fabry disease as well. Taking all the information account we diagnosed the patient with Fabry disease and we conduct yearly follow-up appointments in our centre. We have not found any other reported cases of a combination of TTN and GLA mutations in the literature.
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