ABSTRACT
Aims: T1 mapping in cardiac magnetic resonance imaging enables us to distinguish various myocardial diseases showing left ventricular hypertrophy. Fabry disease is a lysosomal storage disorder causing the accumulation of glycosphingolipids into various organs, including the heart, which can be detected by native T1 values in T1 mapping. However, there is no report for the systematic evaluation of native T1 values in Fabry disease in Japan. Methods and results: We analyzed native T1 values of 30 Fabry disease patients (14 males and 16 females) obtained by 3-T cardiac magnetic resonance imaging. Averaged T1 values were significantly lower in male patients (septal T1: 1149.5 ± 63.3 ms; total T1: 1145.1 ± 59.5 ms) than in female patients (septal T1: 1210.5 ± 45.5 ms; total T1: 1198.8 ± 51.8 ms) (p < 0.01). We compared the native T1 values of Fabry disease patients with those obtained from 15 hypertrophic cardiomyopathy patients (9 males and 6 females). Native T1 values effectively differentiate Fabry disease from hypertrophic cardiomyopathy (septal T1: sensitivity 93.3% and specificity 80.0%; total T1: sensitivity 86.7% and specificity 73.3%). In addition, native T1 values had a significant negative correlation with the left ventricular mass index in male patients at the pre-hypertrophic stage (p < 0.05). In male and female patients without late-gadolinium enhancement, native T1 values also had a significant negative correlation with the left ventricular mass index (p < 0.05). Conclusion: These results suggest that native T1 values can be used to discriminate Fabry disease from hypertrophic cardiomyopathy and can reflect the accumulation of glycosphingolipids in cardiomyocytes.
ABSTRACT
Fabry disease is an X-linked metabolic disorder due to a pathogenic mutation of the GLA gene. The accumulation of globotriaosylceramide (Gb3) damages multiple organs, including the heart, kidney and nervous system, especially in classical type Fabry disease. Enzyme replacement therapy (ERT) using recombinant alpha-galactosidase A has been shown to remove Gb3 from organs and to improve the prognosis of Fabry disease. We herein report the case of a 67-year-old classical type Fabry patient who had been treated with ERT for 6 years and who continuously showed a high antibody titer against recombinant alpha-galactosidase A during therapy. A post-mortem examination was performed after sudden death. A histological examination revealed the massive accumulation of Gb3 in various organs, even after long term ERT. In addition to the typical pathological findings as reported in tissue biopsy samples, the serious accumulation of Gb3 in the cardiac conduction system and the endocrine system was detected. Since the start of ERT for this patient might be too late to improve organ damage and prognosis, ERT should be started before the appearance of major organ involvement for the effective elimination of Gb3 and changes in the therapeutic strategy might be considered if the patient shows a high antibody titer against recombinant alpha-galactosidase A.
ABSTRACT
Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT). Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined. Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH. Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.
