Gaucher Disease

What Is Gaucher Disease

GD is caused by a deficiency in the enzyme β-glucocerebrosidase. Deficient enzymatic activity causes glucosylceramide, the enzyme’s substate, to accumulate in cellular lysosomes, most prominently in macrophages. These glycosphingolipid-laden macrophages are called Gaucher cells. They build up in visceral tissues, liver, spleen, and bone marrow. The accumulation causes an array of symptoms, including hepatosplenomegaly and pancytopenia. It also causes bone complications such as non-specific bone pain, bone crises, avascular necrosis, and pathologic fractures.

GD is an autosomal recessive disorder. There are three types of Gaucher disease. Type 1 accounts for almost 90% of all cases and is commonly found among Ashkenazi Jews. Types 2 is characterized by early-onset and is usually fatal by 2 years of age. Type 3 affects the nervous system more severely than Types 1 and 2. 

In early symptomatic disease, enzyme replacement therapy (ERT) is the standard of care. ERT improves GD-related symptoms and significantly reduces disease complications. Carrier screening for GD has changed the phenotype of children with GD, with many being asymptomatic or mildly symptomatic at diagnosis. 

Glucosylsphingosine (lyso-Gb1), is a downstream metabolic product of glucosylceramide and can be used to monitor treated and untreated GD children.¹