Histopathological evidence of Fabry disease in a female patient with left ventricular noncompaction

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase gene. The most frequent cardiac presentation of Fabry disease is cardiomyopathy characterized by left ventricular (LV) hypertrophy, usually concentric. Heart disease in affected females tends to be clinically recognized later than in males and cardiac complications are the most frequently reported cause of death in females with Fabry disease. There are few data regarding the association between Fabry disease and LV noncompaction. We report a case of a 30-year-old asymptomatic woman, heterozygous for a nonsense alpha-galactosidase gene mutation (p.R220X), who presented LV noncompaction on cardiac magnetic resonance imaging, without LV wall hypertrophy. Histopathological examination of myocardial fragments showed marked deposition of glycosphingolipids in cardiomyocytes, confirming the diagnosis of Fabry cardiomyopathy. Based on this finding, the patient was proposed for enzyme replacement therapy. This case illustrates the role of endomyocardial biopsy in the clarification of doubtful or atypical findings related to cardiac Fabry disease, even in heterozygous women, and corroborates the contention that Fabry disease should be included in the differential diagnosis of LV hypertrabeculation/noncompaction.

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

“…The patient’s leukocyte α-Gal activity was moderately decreased (see Table 1), within the usual range for FD females [1], but all her affected male relatives had <1% REA, in agreement with the known association of this mutation with the classical FD phenotype [1, 42]. At 30 years of age, she was diagnosed with an unusual morphological presentation of FD cardiomyopathy, as reported elsewhere [43]. At age 32 years, she remained clinically asymptomatic and with normal UACR.…”

“…The normal lyso-Gb 3 level and of all its other analogs is in agreement with the result of a confirmatory α-Gal enzyme assay in plasma and does not corroborate the bioinformatic and structural modelling predictions of pathogenicity. It is of note that lyso-Gb 3 analog at m/z 836 was also detected in the plasma of two patients diagnosed with cardiac variants of FD, but was not found neither in the p.Arg118Cys hemizygote male, who showed minimal LVH, probably not related to α-Gal deficiency [46], nor in the p.Arg220Ter heterozygote female, who presented left ventricular noncompaction, probably as an early manifestation of cardiac involvement by FD [43]. This finding is particularly interesting in view of the results of a recent study showing that elevated urinary Gb 3 excretion is associated with near-term mortality in non-FD patients with advanced stages of heart disease [54].…”

Left ventricular trabecular layer operates at high ejection fraction: implications for pump function assessment in excessive trabeculation

“…To test the robustness of our findings, we included 4-chamber views publicly available cases [20][21][22][23][24][25][26][27][28][29] of excessive or abnormal trabeculation from https://radiopaedia.org and from publications. 18,[30][31][32][33] The inclusion criterion was available images of both ED and ES.…”

High ejection fraction of the left ventricular trabecular layer of the human heart

“…To test the robustness of our findings, we included fourchamber views of publicly available cases (Barskiy, 2023a(Barskiy, , 2023bKaplan-List, 2023;Keshavamurthy, 2023;Luijkx, 2023aLuijkx, , 2023bO'Rourke, 2023;Sheehy, 2023;Tigges, 2023;Yarmola, 2023) of excessive or abnormal trabeculation from https:// radio paedia. org and from publications (Chan et al, 2019;Martins et al, 2014;Paluszkiewicz et al, 2022;Petersen et al, 2023;Yousef et al, 2009). The inclusion criterion was available images of both ED and ES.…”