Novel myophosphorylase mutation (p.Arg94Pro) with progressive exercise intolerance

Area of Science:

• Muscle physiology and genetics
• Rare genetic disorders
• Myology

Background:

• Glycogen storage diseases (GSDs) are inherited metabolic disorders affecting glycogen metabolism.
• Muscle phosphorylase (MP) deficiency, a type of GSD V, leads to exercise-induced muscle fatigue and pain.
• Genetic mutations in the PYGM gene are the underlying cause of MP deficiency.

Observation:

• A 16-year-old female presented with severe exercise intolerance, exertional weakness, and muscle cramps.
• Symptoms progressed rapidly, involving limb and bulbar muscles.
• A myoglobinuric episode occurred at age 15, preceding the full clinical manifestation.

Findings:

• Homozygosity for a novel missense mutation (c.281G>C) in the PYGM gene was identified.
• This genetic finding explains the patient's unique and severe clinical phenotype.
• The mutation likely impairs muscle phosphorylase function, leading to glycogen accumulation and muscle damage.

Implications:

• This case expands the known spectrum of PYGM mutations and their clinical presentations.
• Understanding this novel mutation aids in diagnosing and managing similar rare muscle disorders.
• Further research into PYGM function can inform therapeutic strategies for glycogen storage diseases.