Gaucher disease (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes). Glucocerebroside can be collected in the spleen, liver, kidneys, lungs, brain, and bone marrow.

Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher’s disease may be treated with enzyme replacement therapy.

The disease is caused by a recessive mutation in a gene located on chromosome 1 and affects both males and females. Gaucher’s disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids.

The disease is named after the French physician Philippe Gaucher, who originally described it in 1882.

Symptoms

Signs and symptoms of Gaucher’s disease can vary widely. Siblings, even identical twins, with the disease may have different levels of severity. Some people who have Gaucher’s disease have no symptoms at all.

Most people who have Gaucher’s disease experience varying degrees of the following problems:

  • Abdominal complaints. Because the liver and especially the spleen can enlarge dramatically, the abdomen can become painfully distended.
  • Skeletal abnormalities. Gaucher’s disease can weaken bone, increasing the risk of painful fractures. It can also interfere with the blood supply to your bones, which can cause portions of the bone to die.
  • Blood disorders. A decrease in healthy red blood cells (anemia) can result in severe fatigue. Gaucher’s disease also affects the cells responsible for clotting, which can cause easy bruising and nosebleeds.

More rarely, Gaucher’s disease can affect the brain, which may cause abnormal eye movements, muscle rigidity, swallowing difficulties and seizures.

Causes

The three types of Gaucher disease are inherited in an autosomal recessive fashion, this means, both parents must be carriers. If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Genetic counseling and genetic testing are recommended for families who may be carriers of mutations.

Each type has been linked to particular mutations. In all, about 80 known mutations are grouped into three main types:

  • Type I (N370S homozygote), the most common, also called the “non-neuropathic” type occurs mainly in Ashkenazi Jews. The median age at diagnosis is 28 years of age, and life expectancy is mildly decreased. There are no neurological symptoms.
  • Type II (one or two alleles L444P) is characterized by neurological problems in small children. The enzyme is hardly released into the lysosomes. Prognosis is poor: most die before the age of three.
  • Type III (also one or two copies of L444P, possibly delayed by protective polymorphisms) occurs in Swedish patients from the Norrbotten region. This group develops the disease somewhat later, but most die before their 30th birthday.

Prevention

Genetic counseling is recommended for prospective parents with a family history of Gaucher disease. Testing can determine if parents carry the gene that could pass on the Gaucher disease. A prenatal test can also tell if the fetus has Gaucher syndrome.

Diagnosis

Gaucher disease is suggested based on the overall clinical picture. Initial laboratory testing may include enzyme testing. As a result, lower than 15% of mean normal activity is considered to be diagnostic. Decreased enzyme levels will often be confirmed by genetic testing. Numerous different mutations occur; sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available, and is useful when a known genetic risk factor is present.

A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase, angiotensin-converting enzyme, and immunoglobulin levels, or by cell analysis showing “crinkled paper” cytoplasm and glycolipid-laden macrophages.

Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher’s disease activity in response to treatment, and may reflect the severity of the disease.

Prognosis

How well a person does depends on the subtype of the disease. The infantile form of Gaucher disease may lead to early death. Most affected children die before age 5. Adults with the type 1 form of the disease can expect normal life expectancy with enzyme replacement therapy.

Gaucher’s disease may increase the risk of:

  • Growth delays in children
  • Gynecological and obstetric problems
  • Parkinson’s disease
  • Cancers such as myeloma, leukemia and lymphoma

Resources

Advocacy Groups and Nonprofit Organizations

Caregiver Action Network

The Caregiver Action Network seeks to improve the quality of life for more than 90 million Americans who care for loved ones with chronic conditions or old age. The nonprofit organization provides free education, peer support and resources to family caregivers across the country.

E-Pal Connection Program

The E-Pal Connections program has been created in order to facilitate communication and develop relationships among children and teens ages 5 – 17 with Gaucher disease. Children and teens, facilitated by their parents, can connect through FaceTime, Skype, email, or another communication method of their choosing.

Expression of Hope

Expression of Hope is a global program featuring works of art by people with lysosomal storage disorders (LSDs).

Gaucher Disease Facebook Group

The Gaucher disease Facebook group is an excellent resource that helps patients with Gaucher disease, family members and friends communicate with and support one another. Patients created and manage this independent, closed Facebook group. An administrator must approve new members.

Many people in the Gaucher community use this group as a way to ask questions to other patients who have been through similar situations. The group should not be used to give or receive medical advice

Little Miss Hannah Foundation

The Little Miss Hannah Foundation seeks to enhance quality of life for young children, and the families of those children, with life-limiting rare diseases. The foundation also helps children with undiagnosed complex medical needs and those who have been placed in hospice or palliative care.

Lysosomal Disease Network

Although individually rare “orphan” conditions, the lysosomal diseases collectively affect 1 in 6,000 individuals and are responsible for a significant disability and disease burden. These diseases have become a test-bed for some of the most innovative and advanced experimental treatments, including treatment agents designed to cross the blood-brain barrier.

The rarity of each lysosomal disease means that no single medical research center has an opportunity to see the entire spectrum, or to acquire sufficient patient numbers to adequately test new therapies. The combined and integrated efforts of the NIH-funded Lysosomal Disease Network focus limited resources into a network of centers with expertise in one or more of these diseases in order to solve major challenges in diagnosis, disease management, and therapy. Solutions to these problems will have direct impact on patients suffering from lysosomal diseases, and important implications for medical practice.

The Patient Advocate’s Chronicle

The Patient Advocate’s Chronicle posts point-of-view articles, analysis, and expert interviews on medical and other areas of interest to the autoimmune and chronic patient community.

Rare New England

The mission of Rare New England is to bring together New England patients and families affected by rare and complex disorders. The organization creates awareness of available resources and offers educational opportunities to improve patient quality of life.

Yahoo Gaucher Disease Discussion Group

This discussion group enables individuals who are concerned with Gaucher disease and similarly genetically-based diseases to network and communicate. This is a membership only group and requires subscription.

Yahoo Gaucher Disease Types 2 & 3 Discussion Group

This is a private discussion group dedicated to parents, family members and caregivers of children who have Gaucher disease type 2 or type 3. It is a membership only group and requires subscription.

Rare Disease Organizations

EURORDIS
A non-governmental patient-driven alliance of patient organizations representing 724 rare disease patient organizations in 64 countries.

National Organization for Rare Disorders
Provides a unified voice for the 30 million people who wake up every day to fight the battle with a rare disease, including parents and caregivers.

Rare Disease Legislative Advocates
A program of the EveryLife Foundation for Rare Diseases designed to support the advocacy of all rare disease patients and organizations.

Genetic Alliance
A nonprofit health advocacy organization that engages individuals, families, and communities to transform health. They create ways to make it easier to find or build solutions in health services and research.

Global Genes
A rare disease patient advocacy organization that aims to build awareness, educate the global community and provide critical connections and resources that equip advocates to become activists for their disease.

Clinical Trials

ClinicalTrials.gov
An online database of publicly and privately supported clinical studies conducted around the world. ClinicalTrials.gov currently lists thousands of studies with locations in all 50 states and in 191 countries.

Genetic Testing

Genetics Home Reference
An online resource from the National Institutes of Health. The website provides easy-to-understand information about genetic conditions and a range of topics. You’ll find basic explanations of how genes work and how mutations cause disorders. It also includes current information about genetic testing, gene therapy, and the Human Genome Project.

National Society of Genetic Counselors
Provides a helpful, easy-to-use online directory to help connect physicians, patients, and other genetic counselors. Search by state, city, counselor’s name, institution, work setting, type of specialty, or zip code.

Resources for Families and Caregivers

Rare Share
A unique social hub building communities for patients, families, and healthcare professionals affected by rare disorders.

Caregiver Action Network (CAN)
The nation’s leading family caregiver organization working to improve the quality of life for the more than 90 million Americans who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. CAN (formerly the National Family Caregivers Association) is a nonprofit organization providing education, peer support, and resources to family caregivers across the United States free of charge.

Center for Parent Information & Resources
A central resource of information and products to the community of Parent Training Information Centers and the Community Parent Resource Centers so they can focus their efforts on serving families of children with disabilities.

Family Caregiver Alliance (FCA)
A community-based nonprofit organization that that aims to illuminate the caregivers’ daily challenges to better the lives of caregivers nationally, provide them the assistance they need, and champion their cause through education, services, research and advocacy. FCA offers programs at national, state, and local levels to support and sustain caregivers.

Family Voices
Family Voices aims to achieve family-centered care for all children and youth with special health care needs and/or disabilities. Throughout their national grassroots network, they provide families resources and support to make informed decisions, advocate for improved public and private policies, build partnerships among families and professionals, and serve as a trusted resource on health care.

OurKids
An email list of family of parents, caregivers and others who are working with children with physical and/or mental disabilities and delays.

Parent to Parent USA
Programs offering parent-to-parent support as a core resource for families with children who have a special health care need, disability, or mental health issue. Through a one-to-one “match,” experienced support parents provide emotional support to families and assist them in finding information and resources.

Sibling Support Project
A national program dedicated to the lifelong and ever-changing concerns of the millions of brothers and sisters of people with special health, developmental and mental health concerns.

The Bully Project
Inspired by the award-winning film BULLY, this social action campaign includes tools for educators to spark meaningful conversations about bullying.

The Parent Advocacy Center for Educational Rights (PACER Center)
PACER Center is a parent training and information center for families of children and youth with all disabilities from birth to young adults. Parents can find publications, workshops, and other resources to help make decisions about education, vocational training, employment, and other services for their children with disabilities. PACER’s National Bullying Prevention Center provides resources designed to benefit all students, including those with disabilities.

General Health Resources

Agency for Healthcare & Research Quality (AHRQ)
Aims to provide evidence to make health care safer, higher quality, more accessible, equitable and affordable, and to work with the US Department of Health and Human Services and with other partners to ensure that the evidence is used and understood.

Health Hotlines (National Library of Medicine)
A community service to help the public locate health-related information.

Social Security Administration Compassionate Allowances Program
Provides a way of quickly identifying diseases and other medical conditions that may qualify for financial assistance.

Center on Technology & Disability
Designed to increase the capacity of families and providers to advocate for, acquire, and implement effective assistive and instructional technology practices, devices, and services for those who suffer from disabilities.

National Human Genome Research Institute
Developed with the goal of mapping the human genome, the group provides a list of resources for financial assistance with genetic testing.

National Library of Medicine
Provides guidance on how to find reliable information online regarding human genetics.

Patient Advocate Foundation
Provides professional case management services to individuals facing barriers to healthcare access for chronic and disabling disease, medical debt crisis, and employment-related issues at no cost.