Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report

Area of Science:

• Genetics and rare diseases
• Biochemistry and metabolic disorders
• Nephrology and cardiology

Background:

• Fabry disease (FD) is an X-linked lysosomal storage disorder due to alpha-galactosidase A (α-Gal A) deficiency.
• Accumulation of glycosphingolipids impairs organ function, necessitating early diagnosis and treatment.
• Enzyme replacement therapy (ERT) is a key treatment, but its efficacy depends on timely intervention.

Observation:

• A female patient with progressive chronic proteinuric kidney disease was diagnosed with Fabry disease.
• Genetic analysis revealed the pathogenic GLA gene mutation c.870G>C (p.Met290Ile; M290I).
• The patient exhibited cardiac and neurological complications, alongside elevated globotriaosylsphingosine (LysoGb3) levels.

Findings:

• The p.M290I mutation, previously poorly characterized, was associated with significant clinical manifestations of Fabry disease.
• This report provides strong evidence for the pathogenicity of the p.M290I mutation.
• The patient's clinical progression and biomarker changes prompted the initiation of ERT.

Implications:

• This case underscores the importance of considering Fabry disease in patients with unexplained kidney disease, even in female heterozygotes.
• Early identification and characterization of pathogenic GLA mutations, like p.M290I, are crucial for effective management.
• The findings support ERT as a viable treatment option for FD patients with confirmed pathogenic mutations and progressive disease activity.