Fabry disease: Two females with predominant and important cardiac involvement. New mutation for cardiac variant?

• Published in: Archives of Cardiovascular Diseases Supplements Vol. 14; no. 1; p. 42
• Main Authors: Laraba, N., Menzou, F., Moulay, S., Bendimerad, M.I., Abbaci-Deghor, K., Berrah, A.
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.01.2022
• ISSN: 1878-6480
• DOI: 10.1016/j.acvdsp.2021.09.094

Despite the X link, Femal with Anderson-Fabry disease can develop severe signs and symptoms of the disease, although there is considerable phenotypic heterogeneity, which correlates most closely with age. We report the case of two sisters (DN-DM) who carry a non-sense heterozygous mutation with insertion of nucleotide c. [931dupC], not known to express a cardiac variant but classical form. The extracardiac manifestations are minor: No angiokeratoma, no renal failure but microalbuminuria is detected in DM and on cerebral MRI a few punctiform sub-tentorial demyelinating lesions are observed in DM. only verticillata cornea and acroparesthesias are observed. Both patients report dyspnea (more severe in DN) but no angina. On the EKG, there is a shortening of the PR interval and massive LVH: sokolow index is 60mm (DM) and 83mm (DN). On echocardiography, LVH is underestimated, especially for DM. LV diastolic function is altered in both patients: more severely in DN (E/A=2.3). LVEF remains normal. There is no dysfunction of the RV. No segmental or global kinetics problem is observed. The patients present with a thickening of the mitral valve with a slight insufficiency. Aortic insufficiency is noted in DN without dilatation of the initial aorta. DN and DM show impairment of longitudinal function with a global longitudinal strain of -9.5 (Fig. 1, Table 1) and -10 respectively. On cardiac MRI, DM presents myocardial hypertrophy involving the apical antrior and apical lateral, and apical inferior segments as well as the apex of the LV without an area of fibrosis or godalinium enhancement. This hypertrophy distribution exlplains the normality of echo LV mass. DN has greater and more extensive circumferential hypertrophy than DN without fibrosis or gadolinium enhancement. Our mutation, although heterozygous, has an almost exclusive and severe cardiac expression with uncommon topography of LV hypertrophy.