A monozygotic twin pair with highly discordant Gaucher phenotypes

Area of Science:

• Genetics
• Metabolic Disorders
• Neurology

Background:

• Gaucher disease is a lysosomal storage disorder caused by GBA1 gene mutations.
• Monozygotic twins share identical genetic material, typically exhibiting similar phenotypes.
• Consanguinity in parents can increase the incidence of recessive genetic disorders.

Observation:

• Describes monozygotic twins from a consanguineous Moroccan family with discordant Gaucher disease manifestations.
• Both twins are homozygous for the N188S Gaucher genotype, a mutation often associated with milder forms of the disease.
• One twin presents severe visceral, epileptic, and cerebellar symptoms, while her sister is asymptomatic for Gaucher disease.

Findings:

• The study details a rare case of extreme phenotypic discordance for Gaucher disease in monozygotic twins.
• Despite identical N188S/N188S genotype, one twin exhibits severe Gaucher disease, challenging genotype-phenotype correlations.
• The asymptomatic twin has type 1 diabetes mellitus, suggesting potential co-existing or interacting genetic/environmental factors.

Implications:

• This case underscores the complexity of Gaucher disease pathogenesis and the influence of modifier genes or epigenetic factors on phenotype.
• It raises questions about the role of genetic background and environmental influences in disease expression, even in identical twins.
• Understanding such discordance is crucial for accurate genetic counseling and personalized treatment strategies for Gaucher disease and related metabolic conditions.