New mutation in Fabry disease: c.448delG, first phenotypic description

Area of Science:

• Genetics
• Biochemistry
• Neurology

Background:

• Fabry disease (FD) is an X-linked genetic disorder caused by pathogenic variants in the GLA gene, leading to alpha-galactosidase A deficiency.
• Understanding genotype-phenotype correlations is crucial for diagnosing and managing FD, especially with novel mutations.
• This report focuses on a previously uncharacterized GLA gene mutation.

Observation:

• A 38-year-old male presented with positional vertigo, acroparesthesia, anhidrosis, heat intolerance, and abdominal pain since age 10.
• Physical examination revealed nystagmus and angiokeratomas; blood alpha-galactosidase levels were significantly reduced.
• Genetic analysis identified a novel pathogenic deletion mutation, c.448delG, in the GLA gene.

Findings:

• The patient was diagnosed with Fabry disease based on clinical symptoms, low enzyme activity, and the novel c.448delG mutation.
• Family studies indicated this mutation was likely de novo, as no affected relatives were identified.
• This case expands the known spectrum of GLA mutations associated with Fabry disease.

Implications:

• This study contributes to understanding genotype-phenotype correlations in Fabry disease by characterizing a new mutation.
• Early identification and genetic counseling are vital for patients with rare genetic disorders like FD.
• Further research into this specific mutation may reveal unique clinical manifestations or treatment responses.