Akademik Veri Yönetim Sistemi
International Congress of Inborn Errors of Metabolism (ICIEM) 2025, Kyoto, Japonya, 2 - 06 Eylül 2025, (Yayınlanmadı)
Introduction:
Fabry disease (FD) is a X-linked
multısystemic lysosomal storage disorder caused by mutations of the GLA gene.
Deficient activity of α-galactosidase leads to the accumulation of
globotriasylceramide (Gb3) in various tissue. In the heart, GB3 accumulation
leads to ventricular hypertrophy and fibrosis, heart failure, valvular disease,
angina, dysrhythmias, and sudden death. This study aimed to evaluate the role of cardiac involvement in disease
severity and progression using the FOS-Mainz Severity Score Index (FOS-MSSI).
Material and Methods
We
retrospectively reviewed the records of all Fabry patients followed at Dokuz
Eylul University. Data collected included α-galactosidase
activity, lysogb3 levels, and GLA gene variants. We analyzed age at symptom
onset, diagnosis and initiation of treatment; FOS-MSSI. We examined correlations
between cardiac involvement and gender, age, enzyme, lyso GB3 levels. Patients
with and without cardiac involvement were compared.
Results:
Seventeen
patients (30%) were male. The median age of all patients was 41 years
(min:18-max:71), α-Gal A activity was 0.9 μmol/L/h (0-5.7) and lyso-Gb3 level
was 4.8 ng/mL (1.3-113.2). Median α-Gal A activity was 0.2 μmol/L/h(0-1.3) in
males and 1.7(0.1-5.7) in females. Median lyso-Gb3 levels were 24.2 ng/mL
(1.3-113.2) in males and 4.65 (1.3-8.2) in females. Among 27 patients with cardiac involvement, 15 had HCMP,
five had arrhythmia, and seven had HCMP and arrhythmia. Two siblings (one male,
one female) with the GLA c.884delT variant required pacemaker implantation in
the 4th and 5th years of ERT, respectively. Compared to patients without
cardiac involvement, those with involvement had significantly lower α-Gal A
activity(p<0.01) and higher lyso-Gb3 levels(p=0.02). In female
there was no significant difference in enzyme activity between those with and
without cardiac involvement(p>0.05), whereas lyso-Gb3 level was
significantly higher in female patients with cardiac involvement(p=0.029). Age
was significantly higher in female patients with cardiac involvement compared
to those without(p<0.01), although no correlation was found between age and
lyso-Gb3 level in this group(p>0.05). FOS-MSSI was calculated in 29 patients
at presentation: 15 patients were classified as mild, 8 as moderate and 6 as
severe. MSSI score was median 28(13-41) in females with cardiac involvement versus
6(3-37) in females without involvement(p<0.01); 34(20-53) in males with
cardiac involvement and 9 and 19 in two males without involvement(p=0.031).
Conclusion
Cardiac
involvement is common in Fabry patients, especially in males, and in advanced
stages of the disease. Cardiac manifestations are associated with lower enzyme activity
and higher lyso-Gb3 levels, underscoring the importance of early diagnosis and
monitoring for cardiac complications in the management of FD.