Types of Genetic Disorders
There are a number of types of genetic inheritance and associated disorders. For example, single gene or monogenetic inheritance disorders include:
- Iron overload (hemochromatosis)
- Sickle cell anemia
- Marfan syndrome
- Huntington's disease
- Cystic fibrosis
Another type of genetic inheritance is multifactorial inheritance disorders,
- Alzheimer's disease
What is Gaucher disease?
Gaucher disease (sometimes called Gaucher's disease) is an inherited
condition that results in the abnormal accumulation of fatty substances known as
glycolipids in different body tissues due to a deficiency of an enzyme known as glucocerebrosidase. There are several different types of the condition,
and the signs and symptoms that arise due to the sphingolipid accumulation vary
widely. Gaucher disease is due to a genetic defect in a gene known as GBA1.
Gaucher disease belongs to a class of diseases called lysosomal storage
diseases, named after a type of cell that is affected by the buildup of
What are the symptoms of Gaucher disease?
The main signs and symptoms of Gaucher disease are:
People with type 1 Gaucher disease usually first notice painless enlargement
of the spleen, anemia, or bleeding and bruising due to low platelet count. The
enlargement of the spleen may become severe and may limit a child's growth due
to the energy required to sustain the enlarging spleen. An enlarged liver and
abnormal liver function tests are also characteristic signs. Skeletal
involvement by Gaucher disease is common and can take the form of bone pain,
fractures of bone, and a defect of the thigh bone (femur).
How is Gaucher disease inherited?
Gaucher disease in inherited in an autosomal recessive pattern, meaning that
both parents must carry a copy of the defective gene in order for a child to be
How common is Gaucher disease?
In people of Ashkenazi Jewish descent Type 1 Gaucher disease (see below) is
more common, and affects 1 out of every 855 people. About 1 out of every 15
people of Ashkenazi Jewish descent are thought to be carriers of the genetic
mutation responsible for Gaucher disease. The other types of Gaucher disease do
not occur more frequently in people of Ashkenazi Jewish heritage. In the
non-Jewish population, Gaucher disease affects 1 out of every 40,000 people.
What are the types of Gaucher disease?
Type 1 Gaucher disease
The most common form of the condition is type 1 Gaucher disease. About 90% of
people with the condition have this type. The signs and symptoms of this type
can vary in their extent of severity. The symptoms can appear in childhood or
may be delayed until adulthood. The brain and spinal cord, or central nervous
system (CNS), are typically not affected by the disease, so this type is
sometimes referred to as non-neuronopathic, meaning that the condition does not
affect nerve cells.
Type 2 Gaucher disease (acute neuronopathic form)
This rare type of Gaucher disease affects the nervous system and is termed
neuronopathic Gaucher disease. Signs and symptoms include
seizures, eye movement problems, and brain damage. Type 2 Gaucher disease is very severe and typically leads to
life-threatening medical problems that begin in infancy.
Type 3 Gaucher disease (chronic neoronopathic form)
Like Type 2 Gaucher disease, type 3 Gaucher is a neuronopathic for of Gaucher
disease that affects the nervous system, but symptoms do not progress as rapidly
as in Type 2. The signs and symptoms may appear in infancy or later in
Perinatal lethal Gaucher disease
Perinatal lethal Gaucher disease is the most severe form of the condition.
With this type, the life-threatening conditions can appear before birth. There
may be excessive swelling and fluid accumulation in the fetus (hydrops fetalis)
prior to birth. Other features can include severe neurological disturbances,
abnormal facial features, hepatosplenomegaly, and dry or scaly skin. Most
infants with this form of the condition survive only a few days after birth.
Cardiovascular Gaucher disease
This type of Gaucher disease, considered a rare subgroup of type 3 disease,
primarily affects the heart, leading to calcification or hardening of the heart
valves. Sometimes, symptoms and signs of other types of Gaucher disease may also
What causes Gaucher disease?
All of the types of Gaucher disease are caused by a deficiency of the enzyme
glucocerebrosidase, leading to an abnormal buildup of fatty substances,
glycolipids, in the body cells. Mutations in the gene known as GBA1 are the
cause of the deficient enzyme, and over 300 different GBA1 mutations have been
identified in people with Gaucher disease. The mutations are inherited (passed
from parent to offspring) in an autosomal recessive manner (see above). The four
most common mutations of GBA1 gene are N370S, L444P, 84gg and IVS2[+1]. DNA
analysis for these 4 mutations can detect 90%-95% of the mutations associated
with Gaucher Disease in the Ashkenazi Jewish population, and 50%-75% of the
associated mutations in the general population.
Which specialties of doctors treat Gaucher disease?
Patients with Gaucher disease may be treated by a number of different medical
specialists, depending on the type of the disease and the specific symptoms and
signs of the condition they experience. These may include pediatricians,
neonatologists, internists, geneticists, neurologists, orthopedists, critical
care specialists, cardiologists, and hematologists. Most patients who are
treated with enzyme replacement therapy will have their
treatment plan managed by a geneticist and/or hematologist.
Is there a test to diagnose Gaucher disease?
A blood test is used to make the diagnosis of Gaucher disease. The enzyme
assay test measures activity of the glucocerebrosidase enzyme in certain white
blood cells. Having less than 15% of normal enzyme activity is diagnostic for
Gaucher disease. Genetic analysis is also done to establish the specific type of
mutations in the GBA1 gene.
What is the treatment for Gaucher disease?
There is no cure for Gaucher disease, but medical treatments are available.
Enzyme replacement therapy (ERT) is the primary form of treatment for people
with type 1 and Gaucher disease and for the non-neurologic symptoms of type 3
Gaucher disease. The drug is given intravenously, generally at 2-week intervals.
There are three ERT drugs available, imiglucerase (Cerezyme), velaglucerase alfa
(VPRIV), and taliglucerase alfa (Elelyso).
Other medications available to treat Gaucher disease include drugs that block
the production of the sphingolipids that accumulate in cells and cause symptoms.
These drugs are known as glucosylceramide synthase inhibitors and are taken by
mouth. Two drugs in this class are miglustat (Zavesca) and eliglustat
Formerly, the condition was often treated by surgical removal of the spleen
(splenectomy). However, this is typically not necessary given the availability
What is the prognosis, or life-expectancy, for someone with Gaucher disease?
The prognosis for people with type 1 or type 3 Gaucher disease who receive
treatment is very good. Many people with Gaucher disease have few symptoms and
can expect a normal life span even without treatment. One study estimated life
expectancy at birth for people with type 1 Gaucher disease to be 68 years,
compared with 77 years in the general population. Type 2 Gaucher disease usually
results in death within the first few years of life.
Should I talk to my family about Gaucher disease?
As with any inherited disease, sharing information with family members is
important. If Gaucher disease is identified within a family, other family
members may wish to be tested to find out if they are carriers for the gene
mutation. Carrier testing is simple and can be performed on a sample of blood or
saliva. Your health-care professional can help you decide if carrier testing is
appropriate and may refer you to a genetic counselor for more information.
What help is available for patients and their families living with Gaucher
Living with Gaucher disease or any chronic illness is stressful for both
patient and family. Getting help and support are important for achieving the
best quality of life possible while facing the challenges and that the illness
brings. The National Gaucher Foundation (800-504-3189) offers educational and
support services for affected families, including a mentor program, an
electronic pen pal program for young adults, real-life patient stories, and
numerous educational programs.
What other names are used to refer to Gaucher disease?
Gaucher disease has been referred to in the medical literature by a number of
different names. These include:
- cerebroside lipidosis syndrome
- Gaucher splenomegaly
- Gaucher syndrome
- Gaucher's disease
- Gauchers disease
- glucocerebrosidase deficiency
- glucosyl cerebroside lipidosis
- glucosylceramidase deficiency
- glucosylceramide beta-glucosidase deficiency
- glucosylceramide lipidosis
- kerasin histiocytosis
- kerasin lipoidosis
- kerasin thesaurismosis
- lipoid histiocytosis (kerasin type)
National Gaucher Foundation. "Testing for Gaucher disease."
Sidransky, E., MD., et al. "Gaucher disease. Medscape. Updated Nov 24, 2014.
US National Library of Medicine; Genetics Home Reference. "Gaucher disease." Updated July 5, 2016.