Glycogen Storage Disease Due To Lamp-2 Deficiency
Glycogen storage disease due to LAMP-2 (Lysosomal-Associated Membrane Protein 2) deficiency is a lysosomal glycogen storage disease characterised by severe cardiomyopathy and variable degrees of muscle weakness, frequently associated with intellectual deficit.
Epidemiology
More than 20 families have been described in the literature so far.
Clinical description
The disease classically manifests in males over 10 years of age. The clinical picture may be severe in both sexes, but onset generally occurs later in females.
Etiology
The disease is caused by mutations in the LAMP2 gene, localised to Xq24. The LAMP2 protein is an essential component of the lysosomal membrane and appears to play a role in autophagosome-lysosome fusion.
Diagnostic methods
Biological diagnosis revolves around demonstration of normal or high acid maltase activity in combination with muscle biopsies showing large vacuoles (filled with glycogen and products of cytoplasmic degradation) and an absence of the LAMP-2 protein on immunohistochemical analysis. The diagnosis can be confirmed by molecular analysis of the LAMP2 gene. Identification of LAMP2 mutations allows diagnosis of both female and male carriers in affected families.
Differential diagnosis
The differential diagnosis should include X-linked myopathy with excessive autophagia (XMEA) and glycogen storage disease type 2 (see these terms).
Antenatal diagnosis
Prenatal diagnosis is feasible for affected families once the disease-causing mutation has been identified.
Genetic counseling
The disease is transmitted as an X-linked recessive trait. Genetic counselling is complicated by the heterogeneous nature of the disease, even in males from the same family.
Management and treatment
There is no specific treatment for this disease. Symptomatic treatment is required for the cardiac manifestations and patients may require a heart transplant.
Prognosis
Patients are at risk of sudden death due to arrhythmia during early adulthood.