Fatal Case of Exercise Collapse Associated with Sickle Cell Trait with Novel Underlying LAMA2 Mutation

Area of Science:

• Genetics
• Exercise Physiology
• Hematology

Background:

• Sickle cell trait (SCT) is generally considered asymptomatic.
• Exercise Collapse Associated with Sickle Cell Trait (ECAST) is a rare condition linked to SCT.
• Underlying medical conditions can exacerbate ECAST.

Observation:

• A previously asymptomatic, highly active service member experienced ECAST.
• Whole exome sequencing revealed a heterozygous LAMA2 mutation.
• This mutation is novel and not previously documented in literature.

Findings:

• The identified LAMA2 mutation is a likely pathogenic variant.
• This represents the first reported case of ECAST in an individual with this specific LAMA2 mutation.
• The case underscores the role of underlying genetic factors in ECAST development.

Implications:

• This finding expands the understanding of ECAST's genetic underpinnings.
• It suggests genetic screening may be relevant for individuals with unexplained exertional collapse.
• Further research into LAMA2 mutations and their link to exertional syndromes is warranted.