Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome

Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome, also known as Gaucher disease type IIIC or Gaucher-like disease, is an extremely rare variant of Gaucher disease characterized by a distinctive triad of progressive supranuclear ophthalmoplegia (difficulty moving the eyes), cardiovascular calcifications (particularly of the aortic and mitral valves), and mild to moderate splenomegaly. Unlike classic Gaucher disease, this subtype is notable for the prominence of cardiac involvement, which can lead to valvular heart disease, aortic calcification, and potentially life-threatening cardiovascular complications. Corneal opacities and skeletal abnormalities including bone pain and osteoporosis may also be present. Neurological involvement is generally limited to the oculomotor system, distinguishing it from other neuronopathic forms of Gaucher disease. This syndrome is caused by mutations in the GBA gene (encoding the enzyme glucocerebrosidase, also known as acid β-glucosidase), inherited in an autosomal recessive pattern. The deficiency of this lysosomal enzyme leads to accumulation of glucocerebroside in macrophages (Gaucher cells) throughout the body, particularly affecting the spleen, bones, and cardiovascular system. Specific homozygous mutations, notably the D409H (p.Asp448His) mutation, have been strongly associated with this phenotype. Management is challenging because enzyme replacement therapy (ERT), which is effective for type 1 Gaucher disease, has shown limited efficacy in preventing or reversing the cardiovascular calcifications characteristic of this subtype. Supportive care includes monitoring and management of cardiac valve disease, which may require surgical intervention, as well as treatment of skeletal complications. Substrate reduction therapy may also be considered. Regular ophthalmological, cardiac, and hematological monitoring is essential. Due to the progressive nature of cardiovascular involvement, long-term prognosis depends largely on the severity of cardiac disease.

Common questions about Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome