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Phenotype and genotype characterization and twin association in patients with Anderson-Fabry cardiomyopathy
Miquel Gomez1, Lluis Molina, Mercedes Cladellas
1Cardiology Department, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. mgomezpe@parcdesalutmar.cat
Insights
Early enzyme replacement therapy (ERT) can delay clinical outcomes in Anderson-Fabry disease (FD). Screening middle-aged patients with left ventricular hypertrophy (LVH) is crucial for early FD detection, especially in twins.
Area of Science:
- Genetics
- Cardiology
- Metabolic Disorders
Background:
- Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder due to alpha-galactosidase A (α-Gal A) deficiency.
- Cardiac involvement, including cardiomyopathy, is a significant manifestation of FD.
Observation:
- Four adult males with FD, including monozygotic twins, presented with severe left ventricular hypertrophy (LVH).
- Patients exhibited progressive FD symptoms, including angiokeratomas and multi-organ involvement.
Findings:
- All patients showed deficient α-Gal A activity and GLA gene mutations.
- Enzyme replacement therapy (ERT) with agalsidase-alfa was initiated.
Implications:
- Early detection of FD through screening LVH patients is vital.
- Identifying FD in relatives, like twins, can facilitate timely intervention.
- ERT may mitigate disease progression in FD patients.
Abstract:
Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.
