genetic diseases

Symptoms Gaucher disease

Definition

Gaucher disease is a lysosomal storage disease, due to a deficiency of glucocerebrosidase and, in some cases, to the deficiency of the protein activator of saposine C.

Glucocerebrosidase is an enzyme that normally hydrolyzes glucosylceramide (or glucocerebrosides) to glucose and ceramide. Enzyme deficits cause the formation of glucosylceramide and related components in the reticuloendothelial cells of the liver, spleen and bone marrow.

The dysfunction that occurs in Gaucher disease is caused by mutations in the GBA gene (1q21), transmitted in an autosomal recessive manner.

Most common symptoms and signs *

  • anasarca
  • Anemia
  • Apraxia
  • Asthenia
  • Ataxia
  • Convulsions
  • Dementia
  • Dysphagia
  • Bone pain
  • Bruising
  • Hepatomegaly
  • Hydrops Fetal
  • hypersplenism
  • Ophthalmoplegia
  • Corneal opacity
  • Osteopenia
  • Pancytopenia
  • Loss of coordination of movements
  • Growth delay
  • splenomegaly
  • thrombocytosis

Further indications

The symptomology of Gaucher disease is variable, but more commonly includes hepatosplenomegaly and neurological dysfunction.

Based on clinical characteristics, Gaucher disease can be divided into three main forms:

  • Type 1 : represents about 90% of cases; is a chronic and non-neurological form, in which we find the association of hepatosplenomegaly (increase in the volume of the liver and spleen), skeletal pathology (pain, osteopenia, osteolytic lesions with fractures, bone infarcts and osteonecrosis) and cytopenia (thrombocytosis, anemia and, rarely, neutropenia). The symptomatology also includes ecchymoses, pinguecules, delayed growth and delayed puberty. The onset fluctuates from the age of 2 to late adulthood.
  • Type 2 : acute neurological form, characterized by alterations of the central nervous system (eg stiffness, convulsions, etc.) with early onset (during the first year of life) and rapid evolution. Also in this case hepatosplenomegaly is found.
  • Type 3 : subacute neurological form, characterized by progressive encephalopathy (progressive dementia and ataxia, oculomotor apraxia, epilepsy and supranuclear paralysis with corneal opacity) associated with the symptoms present in type 1 Gaucher disease, with the difference that occurs in childhood or adolescence.

Diagnosis can be confirmed by measuring glucocerebrosidase levels in white blood cells.

Enzyme replacement therapy with placental or recombinant glucocerebrosidase (analogue of imiglucerase or miglustat) is an effective approach for patients with type 1 and type 3 disease; unfortunately, no specific drugs are available for type 2 Gaucher disease. Sometimes splenectomy may be indicated when the size of the spleen leads to disorders or in cases with anemia, leukopenia and thrombocytopenia. Bone marrow or stem cell transplantation provides a definitive cure, but is considered an extreme resource due to high morbidity and mortality.