Carrier rate in Ashkenazi Jews:
Approximately 1 in 100

Carrier rate in the general population:
Unknown, but very rare

Other ethnic groups in which it occurs:
Two-thirds of affected individuals are of a wide variety of ethnicities.

Age of onset of symptoms:
Growth deficiencies can start prenatally.

Symptoms:
The two main features of Bloom's syndrome (BS) are unusually small size and a sun-sensitive, red, skin lesion affecting the face. Although the general health is good, persons with BS are more likely than others to develop infections of the middle ear and lung, diabetes mellitus earlier in life than in the general population and tumors, both benign and malignant, of the standard types and sites that affect other people but in BS arising unusually early in life.

Average lifespan:
Shortened because of the complications mentioned above.

What causes the features of the disease:
Absence or non-function of BLM protein results in an increased number of mutations that arise spontaneously in the various cells of the body and the phenotype Bloom's syndrome.

Treatment or management:
Medical intervention aimed at improving growth in BS has been unsuccessful. The facial skin lesion demands protection from the sun. The diabetes in BS is treated in standard ways. With respect to the cancer proneness: No treatment is available to correct the tendency for excessive numbers of mutations to arise in the cells of persons with BS, however, programs for cancer surveillance can be devised and carried out with the help of a family physician knowledgeable about BS.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
One particular BS-causing mutation, referred to as blmAsh is screened for in the Ashkenazi Jewish population.

Other testing information:
The diagnosis BS is confirmed by cytogenetic analysis. BS is the only clinical disorder that features an increased above normal frequency of sister chromatid exchange.

Current research:
Determination of the biological significance of the BLM protein is the subject of investigation in several basic research laboratories. Other work focuses on the genomic instability featured in the rare inherited disorder Bloom's syndrome and the consequences of somatic mutation on human development and the etiology of cancer. Three mouse models of Bloom's syndrome have been developed.

For more information:
Bloom's Syndrome Foundation
www.bloomssyndrome.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 40

Carrier rate in the general population:
Unknown

Other ethnic groups in which it occurs:
All ethnic backgrounds

Age of onset of symptoms:
Three to nine months

Symptoms:
Symptoms generally include rapidly increasing head circumference, lack of head control, reduced visual responsiveness and abnormal muscle tone such as stiffness or floppiness. Children with Canavan disease cannot crawl, walk, sit or talk. Over time they may suffer seizures, become paralyzed, mentally retarded or blind and have trouble swallowing. Although hearing usually remains a functioning sense, deafness may also result.

Average lifespan:
Three to ten years although survival into the 20's has been noted.

What causes the features of the disease:
Canavan disease is a fatal genetic neurological disorder that causes deterioration of the white matter (myelin) in the brain. The white matter forms a protective coating around every nerve in the brain and spinal cord, to ensure that nerve impulses are properly transmitted from one part of the body to another. In children afflicted with Canavan Disease, a gene mutation prevents the production of a critical enzyme called apartoacyclase. Without this enzyme, an acid called NAA or N-acetylaspartate is not broken down, thereby accumulating to dangerous levels in the brain. This is thought to cause catastrophic effects to the normal formation of the white matter.

Treatment or management:
There is no cure for Canavan disease. Treatment involves managing the symptoms of the disease.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
A 98% detection rate is achieved by screening for two mutations.

Other testing information:
Canavan disease can be identified by a simple prenatal blood test that screens for the missing enzyme or for mutations in the gene that controls aspartoacylase.

Current research:
To date, there is no cure or effective treatment for Canavan disease, but several approaches are currently being explored. The first is gene therapy, in which functional aspartoacylase (ASPA) genes are introduced into an affected child's brain to increase the levels of aspartoacylase. The second is the introduction of functional neuronal stem cells into an affected child's brain to increase the number of neurons that make aspartoacylase. The third is the use of medications to reduce the amount of fluid and/or decrease the amount of NAA in a child's brain. The gene for Canavan disease has been located. Research includes studies to understand how the brain and nervous system normally develop and function and how they are affected by genetic mutations. These studies contribute to a greater understanding of gene-linked disorders such as Canavan disease, and have the potential to open promising new avenues of treatment.

For more information:
Canavan Foundation:
(877) 4-CANAVAN or (212) 873-4640
www.canavanfoundation.org
Canavan Research Foundation:
(203) 746-2436
www.canavan.org
Canavan Research Illinois:
(800) 833-2194
www.canavanresearch.org
Jacob's Cure:
(914) 673-2796
www.jacobscure.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 25-30

Carrier rate in the general population:
1 in 25-30

Other ethnic groups in which it occurs:
All ethnic backgrounds, most common in people of Northern or Central European descent.

Age of onset of symptoms:
Infancy; milder forms in older individuals.

Symptoms:
Symptoms are variable, and include frequent lung infections, coughing or wheezing, fat malabsorption, poor growth, fatigue and infertility in males.

Average lifespan:
Many people with Cystic fibrosis (CF) now live into their 30's and 40's. The median age of survival for individuals with CF was nearly 37 years in 2005.

What causes the features of the disease:
A genetic mutation causes the body to produce thick, sticky mucus that clogs the lungs and impairs organ functions.

Treatment or management:
There is no cure for Cystic fibrosis. Current treatment focuses on airway clearance, nutrition and drug therapies. There are over 115 specialty care centers accredited by the Cystic Fibrosis Foundation in the United States.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Over 1,000 mutations have been identified that can cause CF. In the Ashkenazi Jewish population, screening for 5 mutations provides a detection rate of 97%.

Other testing information:
Newborn screening is common to identify individuals who are affected with the disease.

Current research:
Research is currently being conducted to increase understanding of the disease, to develop new therapies and improve treatment, and to explore potential drugs aimed at the cause and symptoms of the disease. Several multi-disciplinary research centers for CF exist at major universities.

For more information:
Cystic Fibrosis Foundation:
www.cff.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 27

Carrier rate in the general population:
Unknown

Other ethnic groups in which it occurs:
Unknown

Age of onset of symptoms:
Birth

Symptoms:
FD causes dysfunction of the autonomic and sensory nervous systems. It is a progressive disease. Symptoms and severity vary in each patient.
Symptoms include:
· Absence of overflow tears / corneal drying
· Poor suck at birth
· Drooling
· Swallowing & feeding problems
· Hypotonia / poor muscle tone
· Short stature
· Delayed developmental milestones: motor, language, social
· Inappropriate temperature controls
· Wide swings in blood pressure
· Gastro-esophageal reflux
· Frequent lung infections or pneumonias
· Episodic vomiting
· Decreased or no reaction to pain and temperature
· Excessive sweating
· Blotchy reddening of skin with excitement and/or feeding
· Smooth tongue / lack of taste buds
· Spinal curvature
· Poor weight gain and growth
· Impaired renal function
· Osteoporosis and osteopenia
· Fainting and cardiac arrhythmias
· Sleep apnea
· Restrictive lung disease

Average lifespan:
Currently, the mean age of the FD population is approximately 15 years. By statistical projection, babies born with FD in 2006 have a 50% chance of surviving to 40 years of age.

What causes the features of the disease:
Inefficient gene splicing results in decreased production of a vital protein called IKAP.

Treatment or management:
Treatments are supportive and preventative. Supportive therapies include medications to maintain and regulate cardiovascular, respiratory, and gastrointestinal function. Surgical interventions include fundoplication, gastrostomy, spinal fusion, and tear duct cautery.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
One mutation is responsible for over 99% of all cases of FD. A second mutation accounts for all other cases except one. A third mutation is responsible for a single case of FD. Carrier testing is available for the two most common mutations.

Other testing information:
Carrier screening is based on DNA analysis.

Current research:
Research focuses on modifying the splicing defect in order to increase production of IKAP as well as to further understand the role of this vital protein. Researchers are also constructing an FD mouse model to further this aim. Clinical investigations include assessment of sleep physiology and assessment of molecular and functional biomarkers.

For more information:
Dysautonomia Foundation:
(212) 279-1066
www.familialdysautonomia.org
FD Hope:
(203) 746-2436
www.fdhope.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 89

Carrier rate in the general population:
Estimated to be approximately 1 in 300 in the United States.

Other ethnic groups in which it occurs:
All ethnic groups; increased frequency in the Afrikaner population in South Africa.

Age of onset of symptoms:
Some physical features noted at birth may suggest this disease.

Symptoms:
The main features of Fanconi anemia are bone marrow failure, short stature, and a predisposition to certain cancers. Other symptoms vary, but may include limb and skeletal anomalies, kidney problems, skin discoloration, small head or eyes, mental retardation or learning disabilities, low birth weight, gastrointestinal difficulties and other defects.

Average lifespan:
Shortened because of the complications mentioned above.

What causes the features of the disease:
In individuals with Fanconi anemia, the system that repairs damaged DNA malfunctions, leading to extensive chromosome breakage.

Treatment or management:
Bone marrow transplantation is the only long-term treatment solution for some of the effects of Fanconi anemia. Shorter-term treatment options include the use of androgens (male hormones) and growth factors. Additionally, routine surveillance for the development of various types of cancer is imperative.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Ashkenazi Jews are screened for one mutation that causes Fanconi Anemia Type C. This mutation has not been found in other populations.

Current research:
The primary areas of current research include the development of treatments for patients suffering from Fanconi anemia; the improvement of the scientific community's understanding of the disease process; and the advancement of diagnostic tools used to identify malignancies and other complications of the disease.

Determination of the biological significance of the BLM protein is the subject of investigation in several basic research laboratories. Other work focuses on the genomic instability featured in the rare inherited disorder Bloom's syndrome and the consequences of somatic mutation on human development and the etiology of cancer. Three mouse models of Bloom's syndrome have been developed.

For more information:
Fanconi Anemia Research Fund:
www.fanconi.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 15

Carrier rate in the general population:
1 in 100-200

Other ethnic groups in which it occurs:
All

Age of onset of symptoms:
Can manifest at any age.

Symptoms:
Gaucher warning signs include fatigue, bleeding problems and easy bruising, enlarged abdomen, bone pain, easily fractured bones, enlarged liver or spleen, low platelet count and anemia.

Average lifespan:
Individuals with Type I Gaucher disease typically have a life span of 6 to 80 years. Within families in which Type I Gaucher disease is present, the severity of the condition varies immensely, thereby making it impossible to determine which family members will suffer from the most severe symptoms. The disease course is quite variable, ranging from no outward symptoms to severe disability and death.

What causes the features of the disease:
Gaucher disease results from a specific enzyme deficiency in the body, caused by a genetic mutation received from both parents. This enzyme deficiency leads to the buildup of a harmful substance in various organs in the body, including the spleen, liver, and bones.

Treatment or management:
1) Enzyme Replacement Therapy is currently the Standard of Care for Gaucher disease. The enzyme replacement therapy in use is Cerezyme®. However, due to many variables, method of care for each individual may vary.

2) The FDA has stated that “Zavesca® is indicated for the treatment of adult patients with mild to moderate Type I Gaucher disease for whom enzyme replacement is not a therapeutic option (e.g., due to constraints such as allergy, hypersensitivity, or poor venous access).” The National Gaucher Foundation believes that Zavesca® should only be recommended by physicians who are expert in the diagnosis, treatment, and management of Gaucher Disease. The National Gaucher Foundation's Medical Advisory Board is currently discussing more precise clinical recommendations for the use of Zavesca® in the overall management of Gaucher disease.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Screening for 4 mutations provides a detection rate of approximately 94%.

Current research:
Research efforts are currently focused on improving outcomes for individuals who are affected with Gaucher disease. Trials are being conducted for an oral therapy for Gaucher disease. The current standard of care treatment for Gaucher disease, enzyme replacement therapy, is delivered intravenously.

For more information:
National Gaucher Foundation:
www.gaucherdisease.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 100

Carrier rate in the general population:
Unknown

Other ethnic groups in which it occurs:
Non-Jewish

Age of onset of symptoms:
Birth

Symptoms:
Global developmental delay, retinal degeneration, elevated gastrin level.

Average lifespan:
Unknown

What causes the features of the disease:
Due to the deficiency of the transmembrane receptor protein the patients experience severe neurological disorder.

Treatment or management:
No medical treatment is available at the present time. Intensive physical, occupational and speech therapies are highly recommended for acquisition of skills.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Two mutations.

Current research:
Development of mouse model; study of the gene products to determine the location and function within the human cell.

For more information:
Mucolipidosis IV Foundation:
www.ml4.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 80

Carrier rate in the general population:
Rare

Other ethnic groups in which it occurs:
All ethnic groups

Age of onset of symptoms:
The first few months of life.

Symptoms:
Enlargement of the liver and/or spleen is usually the first symptom to present. Other symptoms include poor growth and progressive mental and physical deterioration.

Average lifespan:
Two to four years of age.

What causes the features of the disease:
Individuals with Niemann-Pick disease lack an enzyme whose function is to break down the harmful build up of certain substances in the body. Due to this enzyme deficiency, the substances accumulate in various organ systems, leading to the symptoms of the disease.

Treatment or management:
Treatment for Niemann-Pick Disease Type A is supportive, and is aimed at the alleviation of symptoms and the improvement of quality of life.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Three mutations account for about 90% of those occurring in the Ashkenazi Jewish population.

Current research:
One of the focuses of current research is the development of gene therapy as a treatment for Niemann-Pick Disease Type A.

For more information:
National Niemann-Pick Disease Foundation:
www.nnpdf.org

Carrier rate in Ashkenazi Jews:
Approximately 1 in 25-30

Carrier rate in the general population:
1 in 250-300

Other ethnic groups in which it occurs:
Celtic (Irish), French & French Canadian, Cajun, and Pennsylvania Dutch.

Age of onset of symptoms:
3-6 months of age.

Symptoms:
Progressive weakness, loss of motor skills, decreased attentiveness, increased startle response with progressive evidence of neurodegeneration, including seizures, blindness, spasticity, and eventual total incapacitation.

Average lifespan:
Less than 4 years

What causes the features of the disease:
Hexosaminidase A (HEX A) deficiency, which leads to the buildup of harmful substances in the brain.

Treatment or management:
Supportive, protection of airway, control of seizures.

Carrier testing - number of mutations screened for and detection rate in the Ashkenazi Jewish population:
Assay of HEX A enzymatic activity in serum, leukocytes or platelets is a highly accurate method for carrier identification. Serum can be used to test all males and those women who are not pregnant and not using oral contraceptives; and, leukocytes or platelets are used to test women who are pregnant; who are using oral contraceptives; and any individual whose serum HEX A enzymatic activity is in an inconclusive range.

Other testing information:
Molecular genetic testing (DNA mutation analysis) has several uses: confirmation of carrier status or diagnosis of symptomatic individuals with borderline enzyme activity; screening of Ashkenazi Jewish individuals for the three common disease-associated mutations which account for between 92% and 94% of carriers in this population; distinguishing pseudodeficiency mutations from disease-causing mutations in individuals with apparent deficiency of HEX A enzymatic activity; identification of the specific disease-causing mutation in an affected individual so that DNA testing can be used for carrier detection in at-risk family members; and to establish both parental mutations in order to be able to do prenatal diagnosis.

Current research:
Central nervous system enzyme replacement or neuronal-corrective gene therapy - experimental and theoretical.

For more information:
Mathew Forbes Romer Foundation:
(561) 477-0337
www.mfrfoundation.org
National Tay-Sachs & Allied Diseases Association New York Area, Inc:
(212) 431-0431 or (888) 354-7788
www.ntsad-ny.org
National Tay-Sachs and Allied Diseases Association:
www.ntsad.org