Rare Disease Report

Chapter 10: Gaucher Disease

Gaucher disease is an inherited lysosomal disorder that affects many of the body’s organs and tissues. The disease is a rare condition, with a prevalence of 1 in 50,000 to 100,000 individuals in the general population. However, it is common among certain populations, such as Ashkenazi Jews, where the prevalence is about 1 in 900 persons.

The disease also is an autosomal recessive disorder, which means that many people are likely carriers but may not know it. The mutation is within the GBA gene that regulates the synthesis of beta-glucocerebrosidase, an enzyme that breaks down glucocerebroside. It is the excessive accumulation of glucocerebroside in cells and organs that lead to the symptoms observed in Gaucher disease.

There are 3 types of Gaucher disease. Type 1, also called non-neuronopathic Gaucher disease because the brain and spinal cord are generally not affected, is the most common form of the disease. Types 2 and 3 tend to affect the brain, that is, they are neuropathic and non-neuronopathic diseases. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy These patients typically do not live past the age of 2 or 3 years. Progressive degeneration in the brain, especially in the brainstem usually leads to death. Type 3 Gaucher disease also affects the nervous system, but symptoms tend to not be as severe. Seizures and intellectual disabilities are common in these patients, in addition to organomegaly. Symptoms vary greatly in these patients. Further, due to the rarity of both type 2 and type 3 forms of the disease, is it not clear why they have neuronal involvement wheras type 1 patients typically do not.

Signs and Symptoms
  • Painless hepatomegaly and splenomegaly.
  • Hypersplenism and pancytopenia
  • Severe pain associated with joints and bones occurs
  • Neurological symptoms:
Type 1: impaired olfaction and cognition
Type 2: serious convulsions, hypertonia, mental retardation, and apnea
Type 3: myoclonus, convulsions, dementia, and ocular muscle apraxia
  • Osteoporosis
  • Yellowish-brown skin pigmentation
Since the disease runs in families, diagnosing 1 person with Gaucher disease can help other family members learn if they have the disease. Because it is often a slow, progressive disease, it may be years before a person gets diagnosed. Abnormalities in blood tests and joint pain may contribute to this delay.

Blood tests:
  • Glucocerebrosidase levels (<15% of normal) can confirm a diagnosis of Gaucher disease.
  • A complete blood count can help determine the extent of cytopenia
Genetic tests:
  • GBA1 mutations may indicate a person has the condition
Patients with Type 1 Gaucher disease has several medications available for treatment: enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).

Enzyme Replacement Therapy:
    • Cerezyme (imiglucerase for injection) is the gold standard for ERT and has been treating people with Gaucher disease since 1994. It is administered by intravenous infusion every 2 weeks.
    • Vpriv (velaglucerase alfa for injection) was approved in March 2010. It is also administered by intravenous infusion every 2 weeks.
    • Elelyso (taliglucerase alfa) was approved by the FDA in June 2012. It has not been approved for use in Europe based on the argument that Elelyso and Vpriv are too similar. The key biochemical difference of Elelyso compared with the above ERTs is that it is derived from plant (carrot). It is also administered by intravenous infusion every 2 weeks.
  • Substrate Reduction Therapy:
    • Zavesca (miglustat) is for patients who cannot take ERT. Approved by the FDA in July 2003, it is an oral medication taken 3 times per day.
    • Cerdelga (eliglustat) is the first non-ERT that can be used instead of ERT (unlike Zavesca that is only approved for patients who cannot take ERT). It was approved in 2014 and is taken orally once a day.
Patients with Type 2 or 3 Gaucher disease are often treated for their neurological symptoms (seizures, etc); however, they may not benefit from the above medications. More studies are needed to establish their safety and efficacy. Due to the rarity of the conditions, patients should be managed by a doctor familiar with Gaucher disease.

The National Gaucher Foundation is the primary advocacy group in the United States. It has a mentor program that connects patients and families dealing with the disease. The website hold a wealth of resources about screening, treatment options, financial support, and clinical trials, as well as a map to help find Gaucher specialists and specialty centers nearby.
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