A Pathogenic Galactosidase A Mutation Coexisting With an MYBPC3 Mutation in a Female Patient With Hypertrophic...

Area of Science:

• Genetics
• Cardiology
• Histopathology

Background:

• Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition often linked to genetic factors.
• Accurate diagnosis is crucial for effective management and understanding disease mechanisms.
• Identifying coexisting mutations can offer insights into disease heterogeneity.

Observation:

• A female patient presented with hypertrophic cardiomyopathy.
• Histological examination revealed abundant cellular vacuolization and osmiophilic lamellar bodies.
• Immunohistochemistry confirmed the presence of Globotriaosylceramide (Gb3).

Findings:

• Coexistence of mutations in the GLA (Glycosylceramidase) gene (Pro259Ser, c.775C>T) and the MYBPC3 (Myosin Binding Protein C3) gene (c.1351+2T>C) were identified.
• The observed cellular and immunohistochemical findings (vacuolization, osmiophilic lamellar bodies, positive Gb3) are suggestive of Fabry disease.
• This case presents a diagnostic challenge due to the overlapping phenotypes of Fabry disease and HCM.

Implications:

• The findings underscore the necessity of a systematic search for unusual histological and molecular findings in patients with hypertrophic cardiomyopathy.
• Ruling out phenocopies, such as Fabry disease presenting with cardiac symptoms, is critical for appropriate patient care.
• This case contributes to understanding the genetic and phenotypic spectrum of cardiomyopathies and lysosomal storage disorders.