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Alpha-1 Antitrypsin Deficiency can result in life-threatening liver disease in children and adults or in lung disease in adults. Alpha-1 originates in the liver and can lead to liver failure at any time in life. It is the leading genetic cause of liver transplantation in children. Currently, the only treatment for liver disease caused by Alpha-1 is a liver transplant. This disorder is most common in individuals of Northern European Caucasian descent. Alpha-Thalassemia results in severe anemia and, in some forms, death of the fetus or newborn. This disorder is most common in individuals of Mediterranean, Asian, Southeast Asian, Indian, Caribbean, Mexican or Central American ancestry. Carrier frequency varies but may be as high as 1:20. Beta-Thalassemia causes severe anemia in children and requires frequent blood transfusions. Children may grow poorly, have bone deformities or fractures, and develop heart failure from their disease. Beta-Thalassemia, caused by a reduced amount of the normal adult form of hemoglobin (hemoglobin A (HbA), which carries oxygen to the tissues in the body), can range in severity from severe anemia and hepatosplenomegaly in the first two years of life to a much milder anemia presenting later in life. Carrier frequency varies with each ethnic group but is estimated at approximately 1:30 in individuals of Mediterranean (mainly Greek or Italian) and Sephardic Jewish descent. Bloom's Syndrome results in small stature and poor resistance to infection. Intelligence is typically normal in this disorder although mild mental retardation has been reported in some cases. No effective treatment is available at this time. The mean age of death is 27 years of age and is usually related to cancer. The carrier frequency in Askenazi Jews is 1:100. Canavan Disease is a severe neurodegenerative disease (progressive leukodystrophy) with clinical onset usually by 3 to 6 months. Common features are hypotonia, poor head control, hyperextension of legs and flexion of arms, gastrointestinal reflux, feeding difficulties, severe mental deficiency, developmental delay, and macrocephaly. Over time, an affected child will develop spasticity, seizures, optic atrophy, and blindness. Death usually occurs within the first decade of life. No effective treatment is available for this condition at this time. The carrier frequency in Ashkenazi Jews is 1:38. Cystic Fibrosis (CF) is common among Caucasians, particularly those of Northern European origin. The disease causes lung infections, difficulty breathing and problems with bowel function, weight gain and growth. Children frequently need to be hospitalized, have physical therapy and take several medications. The average lifespan is 30 years. One in 2,500 Caucasian newborns has Cystic Fibrosis and 1:25 Caucasians carries the CF trait. The carrier frequency is approximately the same in Ashkenazi Jews. Familial Dysautonomia (FD) affects functions of the body such as swallowing, temperature regulation, sensitivity to heat and pain, and tearing of the eyes. Other common characteristics include gastrointestinal dysfunction, such as reflux and vomiting, abnormal respiratory responses to low levels of oxygen and high levels of carbon dioxide in the blood, scoliosis, poor coordination, and postural hypotension. At this time only 50% of patients live to 30 years of age due to cardiovascular, pulmonary, and gastrointestinal problems. The carrier frequency in Ashkenazi Jews is 1:30. Familial Mediterranean Fever (FMF) is characterized by recurrent painful episodes of fever, peritonitis (abdominal pain), pleuritis (lung inflammation leading to painful breathing), and/or arthritis in the hip, knee, and/or ankle, lasting 2-3 days. The most severe complication is amyloidosis, a condition resulting from accumulation of a starch-like glycoprotein (amyloid) in tissues and organs, impairing their function. This can lead to kidney failure and occurs most commonly in untreated Jews of Northern African ethnicity and in patients of Turkish heritage. Severity of symptoms varies between patients and sometimes even among affected members of the same family. Stress and extreme physical exercise have been seen to precipitate attacks. There are no symptoms between episodes. The carrier frequency is between 1:5 and 1:7 in North African Jews, Iraqi Jews, Armenians, and Turks. It is estimated to be as high as 1:5 for Ashkenazi Jews, in whom the disease is much milder. Fanconi Anemia, Type C is characterized by anemia, short stature, learning disabilities or mental retardation. There may also be birth defects of the limbs, heart or kidneys. Risk for leukemia and early death is increased, with most affected individuals dying before age 30. No effective treatment is available for this condition at this time. The carrier rate in Ashkenazi Jews is 1:89. Gaucher Disease, Type 1 causes a specific fatty substance to accumulate in the bone marrow, spleen, liver, and other parts of the body, and can result in anemia, low platelet count, easy bruising and bleeding, bone pain and bone fractures with little trauma. The severity of the disease varies among individuals, making decisions about testing very difficult. Enzyme replacement therapy is available for affected individuals. The carrier frequency in Ashkenazi Jews is 1:12. Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) can cause a hemolytic anemia. The anemia can vary in severity from life-long anemia to rare bouts of anemia to no symptoms. Certain oxidative drugs, infections, or ingestion of fava beans can also induce it. G6PD has different incidences in different ethnic populations. It occurs with highest frequency in areas with a high incidence of malaria, such as Africa, the Mediterranean, and Asia. G6PD is an X-linked recessive disorder with a carrier frequency varying between 1: 4 to 1:20 in tropical Africa, the Middle East, tropical and subtropical Asia, some areas of the Mediterranean, and Papua New Guinea. Glycogen Storage Disease, Types I and III prevents the liver and/or muscle from completely breaking down the stored glycogen to glucose, which is needed for energy production. Individuals with both types may develop hypoglycemia (low blood sugar) with fasting, and will typically have enlargement of the liver because of glycogen accumulation there.
Hereditary Hemochromatosis causes the body to absorb and store too much iron and is the most common iron overload disease. Excess iron is stored throughout the body in organs and tissues including the pancreas, liver and skin. Without treatment, the iron deposits can damage these organs and tissues. Joint pain is the most common complaint of people with hemochromatosis. Other common symptoms include liver cirrhosis, fatigue, lack of energy, abdominal pain, loss of sex drive and heart problems. Symptoms tend to occur in men between the ages of 40 and 60 and in women over age 50. However, many people have no symptoms when they are diagnosed. Approximately 1:8 to 1:12 individuals of Northern European Caucasian ancestry are carriers. Mucolipidosis IV (MLIV) is a progressive disease that affects the brain and nervous system. The specific cause of this disorder has not been identified. Most reported cases of this disease have been severe with onset during the first year of life, but some individuals with milder disease have also been seen. Most patients reach a maximal developmental level of 12 to 15 months and then plateau. MLIV is often misdiagnosed as cerebral palsy. Long-term outcome and life expectancy are unknown. No effective treatment is available. Carrier frequency in Ashkenazi Jews is 1:100. Neural Tube Defects are a class of birth defects affecting the brain and spinal cord. In one type, spina bifida, a piece of the spinal cord protrudes from the spinal column, causing paralysis below the protrusion. In anencephaly, a fatal neural tube defect, the brain and skull are grossly underdeveloped. Neural tube defects occur in about 7 of every 10,000 pregnancies. Women can reduce their chances of giving birth to a child with a neural tube defect if they take a tablet containing 400 micrograms of folic acid each day in the weeks before they become pregnant and throughout their early pregnancies. These defects are more common in individuals of Irish, English, or Welsh ancestry. Niemann-Pick Disease, Type A is caused by a deficiency of an enzyme called sphingomyelinase, which is responsible for breaking down a specific fat in the body. Lack of sphingomyelinase causes an accumulation of this fat in various body organs, particularly in the liver and spleen. There are several subtypes of this condition. Type A is seen with increased frequency in those of Jewish ancestry. In Type A, accumulation also occurs in the brain and nervous system, resulting in rapid deterioration and death at 2-3 years of age. No cure or effective treatment is available. The carrier rate in Ashkenazi Jews is between 1:70 and 1:90. Phenylketonuria (PKU) is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy. Carrier frequency in Northern European Caucasians is approximately 1:50. Sickle Cell Disease causes painful "crises" in affected children and adults, which may occur with varying frequency. Affected individuals also are at risk for poor growth and for childhood death due to infection. Strokes or kidney failure may occur at a young age. While sickle cell disease is most common in Americans of African ancestry, the trait can also be found in individuals from sub-Saharan Africa, Spanish-speaking regions (South America, Cuba, Central America), Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece and Italy. The disease occurs in approximately 1:500 African-American births and between 1:1,000 and 1:1,400 Hispanic-American births. The carrier frequency in African-Americans is approximately 1:12 and roughly between 1:16 and 1:20 in Hispanic Americans. Tay-Sachs Disease is a progressive neurological disorder affecting the gray matter of the brain. Babies with Tay-Sachs Disease are normal at birth. However, at 3-6 months of age, an affected baby will begin to lose developmental skills. Tay-Sachs Disease is caused by a deficiency of an enzyme called hexosaminidase A or hex A. Lack of this enzyme affects the brain and the nervous system, causing rapid and progressive deterioration. This condition is life shortening with death usually occurring by the age of 6. No effective treatment is available at this time. A late-onset form of Tay-Sachs Disease also occurs, although it is rare. Carrier frequency in Ashkenazi Jews is between 1:25 and 1:30. The Tay-Sachs gene is also more common among French Canadians from eastern Quebec and Cajuns from southern Louisiana. Torsion Dystonia is an autosomal dominant disorder (an individual only needs one copy of an abnormal gene to be affected) characterized by sustained, twisting muscle spasms. With time, the frequency and duration of these spasms increase, leading to joint contracture and progressive disability. Children of an individual affected with Dystonia have a 50% chance of inheriting the gene mutation that causes the disease, but symptoms of Dystonia occur in only 30% of the individuals who inherit the gene mutation. There is no cure, but there has been progress in treating dystonia with a variety of medications. Tyrosinemia, Type I is a metabolic disorder that presents as severe liver disease at less than six months of age. If Tyrosinemia-I is unrecognized and untreated, affected infants will die from liver failure within a few weeks or months following the onset of symptoms. A more chronic form of the disorder may lead to progressive, cirrhotic liver disease and a Fanconi-like renal syndrome with loss of phosphate in the urine, rickets and growth failure. Young children and older patients also may have repetitive bouts of neurologic crises. Among patients who do not die from their symptoms in early childhood, a chronic form of the disorder eventually leads to liver failure or hepatocarcinoma and death, usually before 10 years of age. In the general population, carrier frequency is between 1:160 and 1:175. In individuals of French-Canadian ancestry (mainly Quebec), the carrier frequency may be as high as 1:25. This page was updated on 09/23/04 << Back to Chicago Center for Jewish Genetic Disorders |
