Cardiac magnetic resonance diagnosis of Fabry disease leads to incidental diagnosis of Klinefelter syndrome: a case report

Background Fabry disease is an X-linked lysosomal storage disorder resulting in deficient activity of alpha-galactosidase. Males are general more severely affected however heterozygous females can variably express the disease depending on the degree of random X chromosome inactivation (Lyonization). We present a case where cardiac magnetic resonance diagnosis of late onset Fabry Disease leads to an incidental diagnosis of Klinefelter syndrome. Case summary A 55-year-old male was referred for cardiology assessment after developing atrial fibrillation. Echocardiography demonstrated moderate, concentric LVH (left ventricular hypertrophy). Cardiac magnetic resonance imaging confirmed the presence of concentric increase in LV wall thickness and increased LV (left ventricular) mass. T-1 mapping values (Shortened Modified Look-Locker Inversion recovery sequences) were elevated in the basal-mid inferolateral segments and low in the remaining segments. Late gadolinium acquisition showed a pattern suggestive of Fabry disease. Genetic testing of the GLA gene revealed a null variant classified as pathogenic. The variant was found to be heterozygous. This raised the possibility of Klinefelter's syndrome and the diagnosis was confirmed by chromosomal microarray and karyotype. The patient was then referred to Fabry clinic for consideration of enzyme replacement therapy and to the endocrine clinic for testosterone replacement. Discussion The atypical 'cardiac variant' Fabry disease should be included in differential diagnosis of left ventricular hypertrophy. In a 'late onset' presentation of Fabry Disease, the concomitant presence of Klinefelter syndrome cannot be excluded due to GLA variant present in the heterozygous state.