Galactosidase Alpha p.A143T Variant Fabry Disease May Result in a Phenotype With Multifocal Microvascular Cerebral Involvement at a Young Age

Area of Science:

• Neurology
• Genetics
• Metabolic Disorders

Background:

• Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by variants in the galactosidase alpha (GLA) gene.
• Over 600 GLA gene variants have been identified, with varying clinical presentations.
• The p.A143T variant is of unknown significance, with reported phenotypes ranging from classical FD to asymptomatic individuals.

Observation:

• A 16-year-old male presented with headaches and multifocal white matter lesions on brain MRI.
• Significantly reduced alpha-galactosidase A activity and a hemizygous p.A143T GLA gene variant confirmed the diagnosis of FD.
• Baseline assessment revealed only discrete proteinuria, suggesting a predominantly subclinical presentation.

Findings:

• The p.A143T GLA gene variant was associated with a subclinical phenotype in this case.
• Cerebral white matter lesions were a key indicator for FD diagnosis in this young patient.
• This case suggests the p.A143T variant may be linked to a more severe phenotype than previously understood.

Implications:

• Consider Fabry disease in young patients with unexplained cerebral white matter lesions.
• The p.A143T GLA variant may warrant closer monitoring for systemic involvement.
• Further research is needed to fully elucidate the pathogenicity and clinical spectrum of the p.A143T variant.