Overview & Conditions
In the cells of the body there are pairs of genes or ‘instructions’ which tell our bodies how to grow and develop. For each pair, we inherit one gene from our mother and one from our father. When disease or improper development is caused by having two copies of a gene that are not working properly, the disease is called recessive. (When disease or improper development is caused by having one copy of a gene that is not working properly, the disease is called “dominant”.)
In an autosomal recessive condition we must inherit two altered (mutated) genes, one from our mother and one from our father, in order to be affected. The parents are called ‘carriers’ of the condition. Carrier parents are normal and therefore not affected. However, when carrier parents have children, each child has a 1 in 4, or 25% chance to be affected with the disorder.
All humans are thought to carry 10-20 genes which do not work properly. It is impossible to screen an individual for every recessive condition. It is estimated that humans have 30,000 genes and at the present, testing is available for a small percentage. Certain recessive disease-causing genes are more commonly found in different parts of the world, and in persons of different ethnic backgrounds. For example, the gene which causes Tay Sachs disease is most common in the Ashkenazi Jewish population, while the gene for Sickle Cell Anemia is most common in the African American population.
Carrier screening for recessive genes is therefore based on a person’s ethnic background or the presence of a disease in their family history.
Diseases Common in Ashkenazi Jews
There are also specific genetic conditions more commonly seen in the Ashkenazi Jewish population than in the general population. In addition, for some diseases common in the general population, specific mutation testing is possible in individuals of Ashkenazi descent. Below you will find descriptions of 18 conditions; to learn about your specific risk for each, go to the What's My Risk? page.
Tay Sachs Disease is fatal in children (usually by age 5) and involves progressive degeneration of the central nervous system. Absence of an enzyme called hexosaminidase A (or hex A) causes a fatty substance to build up in the brain and spine. The process begins in the fetus prenatally, but is not evident until the child is several months old. To date, there is no cure for Tay Sachs disease.
Canavan Disease is similar to Tay Sachs in that it also involves progressive degeneration of the central nervous system and is fatal in early childhood. The condition is caused by the absence of an enzyme called aspartoacylase (ASPA). To date there is no cure for Canavan disease.
Familial Dysautonomia (FD) is a rare genetic condition involving deficiency of the enzyme beta hydroxylase. The sensory and autonomic nerves (those controlling involuntary functions) are affected, resulting in problems with blood pressure control, temperature regulation, feeding, growth, sensitivity to pain, and others. Early diagnosis and treatment improves prognosis and survival, but there is no cure for the disease.
Cystic Fibrosis (CF) is a condition with a range of clinical severity. People with classic CF secrete abnormally thick body fluids, especially in their lungs. The mucus interferes with normal body functions and leads to chronic infections. Classic CF also involves the pancreas, resulting in decreased absorption of nutrients. Survival rates have improved, but death ultimately occurs from respiratory failure. Some variant forms of CF may have only lung involvement, pancreatitis, sinusitis, or infertility.
Bloom syndrome is caused by a gene defect that results in an increased number of chromosomal breaks. Affected persons generally have short stature, skin color changes and rashes (especially after sunlight exposure), and increased susceptibility to infections and cancer. Mental retardation occurs in some affected individuals. Fertility problems are common in both sexes. While there is no cure for Bloom syndrome, treatment is geared toward prevention of symptoms.
Fanconi anemia, type C is also caused by a gene defect that results in an increased number of chromosomal breaks. This leads to decreased production of blood cells, skeletal abnormalities, and an increased risk of cancer. Onset is usually in childhood, with survival into the late teens or early twenties. Mental retardation, gastrointestinal problems and cardiac abnormalities are seen in some affected individuals. In rare cases, diagnosis is in adulthood, generally because of atypical cancers. Treatment is primarily preventative and includes frequent screenings and avoidance of the sun and agents that cause chromosomal damage.
Gaucher disease, Type 1 is caused by deficiency of the enzyme glucocerebrosidase which results in storage of a fatty substance called glucocerebroside in the spleen, liver, bone marrow and other systems. Onset may be early in life or delayed until adulthood. Symptoms include easy bruising and bleeding, anemia, chronic fatigue, liver and spleen enlargement, bone pain and bone fractures. Highly effective enzyme replacement therapy is available, but there is no cure at this time.
Mucolipidosis, type IV (ML4) is caused by a gene defect that leads to abnormalities of the nervous system and the eyes. The earliest sign of ML4 may be clouding of the corneas in the first year of life, along with delayed motor milestones, mental retardation and slowly progressive neurological deterioration. Affected persons have lived into their mid 40s. Treatment includes supportive care, such as occupational or physical therapy. There is no cure for ML4.
Niemann Pick Disease, type A is caused by lack of the enzyme acid sphingomylinase (ASM), resulting in accumulation of a fatty substance called sphingomyelin, and leading to severe damage to the central nervous system, liver, and lungs. Symptoms beginning in infancy include loss of previously achieved milestones, blindness, progressive spasticity, enlargement of the liver and spleen, and a “cherry red spot” in the back of the eye. There is currently no cure, and death usually occurs by age 2-3.
Glycogen Storage Disease, type 1A (GSD1A) is caused by a lack of the enzyme glucose-6-phosphatase, which breaks down stored sugar into sugar that is usable for energy. As a result, individuals with GSD1A have hypoglycemia (low blood sugar) which can cause weakness and irritability, seizures, coma, and early death. Treatment is lifelong and includes a very strict and complex diet along with small, frequent feedings. Later in life kidney problems, tumors in the liver (benign and malignant), high cholesterol/triglycerides, and gout (painful swelling of joints) may develop. There is no cure for GSD1A.
Maple Syrup Urine Disease (MSUD) is caused by a lack of BCKAD enzyme activity which results in the body’s inability to break down certain amino acids, specifically leucine, isoleucine, and valine. Amino acids are building blocks for protein. If untreated, these amino acids accumulate in the body causing irreversible neurological damage. Symptoms beginning in infancy include fussiness, lethargy, decreased nursing/feeding, poor weight gain, hypotonia (poor muscle tone) or hypertonia (excessive muscle tension), vomiting, a high-pitched cry, seizures and the characteristic maple syrup smell of the urine, which is more noticeable in a diaper after it has dried. MSUD is treatable by restricting leucine, isoleucine, and valine from the diet. Infants are usually screened for MSUD through mandatory state screening programs shortly after birth.
Dihydrolipoamide dehydrogenase deficiency (DLD), also known as Lipoamide dehydrogenase deficiency (LAD), is a rare cause of primary lactic acidosis in children. Lactic acidosis is when lactic acid builds ups in the blood stream faster than it can be removed. This condition is caused by the deficiency of the enzyme DLD. Patients are usually free of symptoms during the first weeks or months of life, except for episodes of hypoglycemia (low blood sugar). Thereafter, they develop progressive neurologic problems such as hypotonia (poor muscle tone), microcephaly (small head size), developmental delay, dystonia (involuntary muscle contractions), ataxia (unsteady movements), enlarged liver, blindness, and coma. There can also be recurrent attacks of vomiting and abdominal pain. Onset of the disease ranges from the neonatal period to adulthood, however, and clinical presentation is variable. Mortality is high and there is no treatment.
Familial hyperinsulinism (FHI) is an inherited disorder of unregulated insulin secretion that causes mild to severe hypoglycemia (low blood sugar). Insulin is a hormone made by the pancreas that controls the level of sugar in the blood. FHI begins in the newborn period to first years of life. If left untreated, FHI can result in irreversible neurological damage or death.
Nemaline myopathy (NM) is a disease of voluntary muscle resulting in muscle weakness, poor muscle tone, and depressed or absent deep tendon reflexes. Deep tendon reflexes are the reflexes that are obtained by tapping on the tendons (such as the "knee jerk"). Muscle weakness is usually most severe in the face, the neck, and the proximal limb muscles. There are six different forms of NM based on age of onset and severity. Significant differences in survival exist between individuals depending on the form, with death in the first few years of life due to respiratory failure in the most severe form.
Usher syndrome type III is an inherited disorder of progressive hearing loss and vision loss beginning in the first few decades of life. Infants with this condition are usually born with normal hearing, with progressive hearing loss beginning sometime during the first two decades of life. By middle age, most affected individuals are profoundly deaf. Vision loss caused by retinitis pigmentosa (an eye disease that damages the retina) develops in late childhood or adolescence. Difficulties with balance due to inner ear problems may also be present. Currently, there is no treatment or cure for Usher syndrome type III.
Usher Syndrome type IF is subtype of Usher Syndrome type I and is an inherited disorder of profound deafness present at birth, severe balance problems, and adolescent-onset vision loss caused by retinitis pigmentosa (an eye disease that damages the retina). Children with this condition walk later than usual. Older children may be described as clumsy and experience accidental injuries or have difficulty with activities requiring balance, such as riding a bicycle or playing sports. The rate and degree of visual field loss varies, however, visual impairment does worsen each year. Currently, there is no treatment or cure for Usher syndrome type 1F.
Joubert syndrome 2 is characterized by the absence or underdevelopment of part of the brain that controls balance and coordination, called the cerebellar vermis. Infants with Joubert syndrome 2 have abnormally rapid breathing (hyperpnea), poor muscle tone (hypotonia), jerky eye movements (oculomotor apraxia), mild to moderate mental retardation, and unsteady movements (ataxia). Other problems that may be present include an inability to control tongue movements, kidney and liver abnormalities, and seizures. There is currently no cure for Joubert syndrome 2.
Spinal Muscular Atrophy is characterized by muscle weakness and, in the most common type, respiratory failure by age two. Muscles responsible for crawling, walking, swallowing and head and next control are the most severely affected. SMA has been known as congenital axonal neuropathy, arthrogryposis multiplex congenita (prenatal SMA), Werdnig-Hoffman disease (SMA type I), Dubowitz disease (SMA type II) and Kugelberg-Welander disease (SMA type III).
Walker-Warburg Syndrome is a severe muscle, eye, brain syndrome. It presents with muscle weakness, feeding difficulties, seizures, blindness with eye and brain anomalies and delayed development. Life expectancy is below 3 years.
Diseases Common in Sephardic Jews
There are specific genetic conditions more commonly seen in the Sephardic Jewish population than in the general population. These genetic conditions are specific to the community of origin and may include beta thalassemia, familial mediterranean fever, G6PD deficiency, and glycogen storage disease type III. Below you'll find descriptions of 4 conditions; to learn about your specific risk for each, go to the What's My Risk? page.
Beta Thalassemia is a group of hereditary disorders characterized by a deficiency in the synthesis of beta-globin chains, a critical component of hemoglobin. People with thalassemia are not able to make enough hemoglobin, which is what causes anemia. Hemoglobin is found in red blood cells and carries oxygen to all parts of the body. When there is not enough hemoglobin in red blood cells, oxygen cannot get to all parts of the body. Organs then become starved for oxygen and are unable to function properly. Blood transfusions are used to treat people with beta thalassemia.
Familial Mediterranean Fever (FMF) usually begins in childhood or during the teenage years, but can also onset later in life. FMF is characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints that may be accompanied by fever and sometimes a rash. Amyloidosis (a buildup of protein deposits) in the tissue and organs can occur and may result in kidney failure and reduced fertility. Treatment includes medication and organ donation. Medication is not effective in all cases.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a defect of the G6PD enzyme which causes hemolysis (the destruction of red blood cells) mostly in males. This is because the gene is located on the X chromosome. Males have one X and one Y chromosome; genes on the Y do not compensate or "match-up" with genes on the X. Females have 2 X chromosomes so that if there is one altered (mutated) gene on one X, the other normal gene copy on the opposite X compensates. Under certain conditions, people with G6PD deficiency will have hemolytic anemia, which is a type of anemia that occurs when red blood cells are destroyed faster than the body can replace them. Infections, some drugs (such as certain antibiotics and medications used to treat malaria), some foods (such as fava beans), or exposure to certain chemicals (such as those found in moth balls) can trigger hemolytic anemia. Symptoms of hemolytic anemia include paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. Discontinuation of exposure to a known trigger, medication to treat infections, and blood transfusions are used to treat hemolytic anemia.
Glycogen Storage Disease type III (GSD III) is caused by a deficiency of the glycogen debrancher enzyme. Without the normal amount of enzyme, the liver and muscle tissue cannot break down stored glycogen into glucose. In turn, glycogen progressively builds up enlarging the liver, and causes muscle wasting and organ failure. GSD III is considered a muscular dystrophy. There is no treatment but some symptoms can be managed through a special diet.