SCIENTIFIC JOURNAL of the Hungarian Society of Cardiology

Does the GLA p.Ala143Thr variant cause Fabry disease?

█ Original article

DOI: 10.26430/CHUNGARICA.2023.53.4.343

Nagy Viktória1, Rácz Gergely1, Takács Hedvig1, Radics Bence2, Borbás János1, Kormányos Árpád1, Csányi Beáta1, Lidia Hategan1, Iványi Béla2, Nagy István3, 4, Hegedűs Zoltán5, 6, Sepp Róbert1
1Szegedi Tudományegyetem, Kardiológiai Centrum, Szeged*
2Szegedi Tudományegyetem, Patológiai Intézet, Szeged*
3Biokémiai Intézet, Szegedi Biológiai Központ, Szeged*
4Seqomics Biotechnológiai Kft., Mórahalom*
5Biofizikai Intézet, Szegedi Biológiai Központ, Szeged*
6Pécsi Tudományegyetem, Biokémiai és Orvosi Kémiai Intézet, Pécs


Background: The differential diagnosis of hypertrophic cardiomyopathy (HCM) and of cardiac manifestations of HCM-mimicking phenocopies, e.g., Fabry disease, can cause significant diagnostic challenges in everyday clinical practice.
Case report: The 55-year-old male patient had a past medical history of hypertension, multiple hospital admissions for hypertensive excess, atherosclerosis, COPD, kidney involvement and stroke. During cardiological assessment, initiated because of dyspnea and effort intolerance, significant left ventricular hypertrophy (IVS: 21 mm, PW: 17 mm) was confirmed, without significant valve disease or left ventricular outflow tract obstruction. The left ventricular ejection fraction was preserved (EF: 64%), with decreased left ventricular global longitudinal strain (GLS: –11.8%) and normal left ventricular filling pressures. Cardiac MRI confirmed the presence of severe left ventricular hypertrophy (LVmax: 22 mm) with diffuse, extensive late contrast enhancement, most pronounced at the basal and inferolateral wall. Laboratory findings showed moderately increased NT-proBNP (427 pg/ml) and troponin T (41 ng/ml) levels, with decreased renal function (eGFR: 59 ml/min/m2) and mild proteinuria. Specific studies for the suspected Fabry disease showed normal lyso-Gb3 and moderately decreased alpha-galactosidase enzyme levels (45% of normal reference value). Genetic testing of the GLA gene confirmed a p.Ala143Thr variant (NM_000169.2:c.427G>A, rs104894845) classified as “variant of unknown significance”. Since imaging studies could neither exclude nor confirm the suspected storage or infiltrative myocardial diseases, myocardial biopsy was performed, which clearly excluded Fabry disease or infiltrative disease, and disclosed abnormalities characteristic of hypertrophic cardiomyopathy (fibrosis, myofiber disarray).
Conclusion: A multidisciplinary approach, including detailed imaging studies, and myocardial biopsy and genetic testing, if necessary, can help differentiate cardiac manifestations of phenocopies that mimic hypertrophic cardiomyopathy.


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