Gaucher disease is characterized by the accumulation of a glycolipid or fatty compound called beta-glucocerebroside, which is a key component of all cell membranes, in different organs and tissues in the body. This occurs because both copies of the gene that encodes for a lysosomal enzyme called beta-glucocerebrosidase, which is responsible for breaking down beta-glucocerebroside and preventing it the compound from building to toxic levels in cells, are mutated.

There are three types of Gaucher disease based on the symptoms patients manifest.

Patients with type 3 Gaucher disease represent about 5 percent of those with this disease. Symptoms of type 3 disease first appear in early childhood (ages 2 to 5), adolescence, and — more rarely — in early adulthood. Disease onset can occur before age 2, but progression is generally slow and patients diagnosed as children often live into full adulthood.

Type 3 Gaucher disease patients have both non-neurological and neurological symptoms. Their neurological symptoms are milder — because of lesser central nervous system involvement — than those seen in patients with type 2 Gaucher disease.

Based on evident symptoms, type 3 Gaucher disease is further classified into four subtypes, called 3a, 3b, 3c, and the less common Norrbottnian variant.

Symptoms of type 3 subtypes

Subtype 3a

Subtype 3a is characterized by mild visceral (organ, bone, body) symptoms but often severe and rapidly progressing neurological symptoms, such as oculomotor apraxia absence of controlled, voluntary, and purposeful eye movement), cerebellar ataxia (lack of fine tuning of voluntary movements because of damage to brain cells), spasticity (constant contraction or stiffness of muscles due to damage to nerve cells in the brain and spinal cord that control voluntary movement), progressive myoclonic epilepsy, and dementia (affecting memory, thinking, and social skills). The prognosis of subtype 3a Gaucher disease is poor and patients can succumb to the disease within the first two decades after diagnosis. But the rate of disease progression can be highly variable in patients with this subtype.

Subtype 3b

Subtype 3b is characterized by severe visceral involvement, including hepatosplenomegaly (enlarged liver and spleen), growth retardation, bone disorders, and skeletal anomalies. Neurological issues are usually milder and slow progressing. The horizontal supranuclear gaze palsy (inability to see in the horizontal direction because of problems in brain cells controlling eye movements) is the major neurologic symptom in this subtype.

Subtype 3c

Subtype 3c is an atypical rare variant that shows considerable clinical overlap between subtypes 3a and 3b. It is characterized by progressive calcification of the cardiac valves causing hardening, thickening, and narrowing the valves, as well as calcification or fibrosis of the aorta, the main artery carrying blood from the heart to the body. Other symptoms include supranuclear gaze palsy or the inability to see in a particular position, either vertical or horizontal; mild spleen and liver enlargement; corneal opacities (clouding of the cornea that decreases vision), hydrocephaly (fluid buildup in the brain); and skeletal anomalies that include bone pain, osteopenia (weaker bones), and fractures.

Norrbottnian variant

Norrbottnian variant is characterized by early onset organ enlargement (hepatosplenomegaly evident as early as age 1) that may require splenectomy (the surgical removal of the spleen), progressive kyphosis (forward curvature of the spine), and mild cognitive deficits. Patients also exhibit hematological symptoms such as anemia, thrombocytopenia (low platelet count), and skeletal problems such as bone pain, osteopenia, acute bone crises, and fractures. Neurological symptoms include horizontal supranuclear gaze palsy, ataxia, mild spasticity in the legs, myoclonic or complex partial epileptic seizures, and cognitive deterioration that can lead to dementia.

Interestingly, this particular subtype is believed to have first appeared in northern Sweden around the 16th century, and today covers about 40 percent of all diagnosed Gaucher cases in that country. A particular mutation — the L444P mutation — defines this variant and may be within this population because of a common ancestry.


Type 3 Gaucher disease patients are primarily treated for visceral symptoms with enzyme replacement therapy (ERT), such as Cerezyme (imiglucerase), Elelyso (taliglucerase alfa), and VPRIV (velaglucerase alfa), all of which are recombinant human enzyme beta-glucocerebrosidase produced by recombinant DNA technology. ERTs work to help replace the defective and disease-causing enzyme in Gaucher patients.

Substrate reduction therapeutics (SRT) are also available as a secondary treatment when ERT response is poor. SRTs include Cerdelga (eliglustat) and Zavesca (miglustat), both of which reduce beta-glucocerebroside production. 
In some cases, a splenectomy may be necessary. Spinal surgery may also be required in cases of severe and progressive spinal abnormalities.


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