Response to Letter Regarding Article, “Contrast-Enhanced Magnetic Resonance Imaging of a Patient With Chloroquine-Induced Cardiomyopathy Confirmed by Endomyocardial Biopsy”
We highly appreciate the consideration on differential diagnoses that Pieroni et al put forward regarding our recently published article1 on the clinical, morphological, and ultrastructural features of a patient with chloroquine-induced cardiomyopathy, a disease in which lysosomal trapping of the amphiphilic drug chloroquine seems to be the underlying pathophysiological mechanism. As emphasized by Pieroni et al, cardiomyopathy associated with Fabry disease, which is based on intralysosomal accumulation of glycosphingolipids attributable to (inborn) α-galactosidase A deficiency, results in intriguingly similar clinical and ultrastructural features, including marked left ventricular hypertrophy, cardiac conduction disorders, and lamellar pseudomyelinoid bodies within cardiomyocytes.
Although it is an X chromosome–linked disease, Fabry disease may also manifest in heterozygote females, resulting in some variations of clinical phenotypes, including isolated cardiac manifestations and variable residual α-galactosidase A activity measured in peripheral leukocytes, probably because of unpredictable lyonization.2
In our patient, a 67-year-old woman, α-galactosidase A activity in peripheral blood leukocytes amounted to 0.47 nmol/min per milligram of protein (normal: 0.4 to 1.0), and, according to DNA analysis of α-galactosidase A–encoding regions, Fabry disease was excluded (polymerase chain reaction, PAGE). Although pseudomyelinoid bodies, a common finding in both diseases, were abundant on electron microscopy of right ventricular endomyocardial biopsies, so-called curvilinear bodies—which, in the article by Roos et al,3 were demonstrated in 2 of 3 patients with chloroquine cardiomyopathy but in none of 3 patients with Fabry cardiomyopathy—were not demonstrated in our patient. Interestingly, late gadolinium enhancement on magnetic resonance imaging seems to be characteristic of both diseases. Whereas in Fabry disease, contrast enhancement seems to predominate in basal/basal-medium segments of the lateral or inferolateral wall,4,5 it was visible in the anterior septal region in our patient with chloroquine-induced cardiomyopathy.
Systematic comparative investigations of both types of cardiomyopathy might be useful for detecting further common and differentiating pathophysiological pathways in both diseases.