Cystic Fibrosis
Cystic Fibrosis is caused by defective gene that controls the movement of salt and water in and out of cells. This eventually leads to an accumulation of mucus in the lungs and digestive system. It primarily affects the white population, and is less common in other ethnic groups. About 1 in 2,500 to 3,500 newborns is born with the disease, while 1 in 25 people are carriers of the gene. In the U.S., about 30,000 people have the disease, while worldwide this number is 70,000. Of those that are born with the disease, 75% are diagnosed by age 2, and half of those with the disease are under the age of 18. Life expectancy for those affected with CF is estimated to be around 35-40 years.
Spinal Muscular Atrophy
Spinal Muscular Atrophy is caused by a defective gene that is important for motor neuron survival. Motor neurons are located in the spinal cord and control muscle movement. With the loss of motor neurons, the muscles are not used and become weaker and weaker. About 1 in 6,000 to 10,000 people are affected, and 1 in 40 to 60 is a carrier of the disease.
Fragile X Syndrome
Fragile X syndrome is caused by a mutated gene on the X chromosome, which switches off a protein involved in brain development. This syndrome is more severe in males than females, as males only have one X chromosome. Those affected experience delayed development of speech and language, anxiety, and hyperactivity, often leading to a diagnosis of ADD with features of autism. Some may experience seizures. The estimated incidence in males is 1 in 4,000, while in females it is 1 in 8,000. The estimated chances of being a carrier are 1 in 151 females, and 1 in 468 males.
Alpha Thalassemia
Alpha thalassemia is caused by deletions of genes important for the production of the alpha chain of hemoglobin, which results in a defective hemoglobin molecule in the red blood cells and thus anemia. It is common among populations of Southeast Asian descent as well as African, affecting 5-30% of these populations. Globally, 1.7% of the world population has either an alpha or beta thalassemia trait, and has an estimated incidence of 4.4 in 10,000 newborns.
Beta Thalassemia
Beta thalassemia is caused by deletions of genes important for the production of the beta chain of hemoglobin production, which results in a defective hemoglobin molecule in the red blood cells and thus anemia. It is common among populations of Mediterranean and Southeast Asian descent, as well as African, affecting 5-30% of these populations. Globally, 1.7% of the world population has either an alpha or beta thalassemia trait, and has an estimated incidence of 4.4 in 10,000 newborns. Worldwide, it affects 1 in 100,000 people.
Sickle Cell Disease
Sickle Cell Disease is caused by abnormal hemoglobin genes that result in crescent shaped red blood cells. These misshapen red blood cells are not flexible like normal red blood cells, and can aggregate and cause blockages that can stop blood flow and prevent oxygen from reaching the tissues. This disease is common in the African American population, affecting 1 in 365 newborns, while 1 in 13 are born with the trait. In the U.S., there is an estimated 100,000 individuals with the disease, affecting 1 in 5,000 people. Globally, it also has a high frequency in sub-Saharan Africa, India, and the Middle East.
Bloom’s Syndrome
Bloom’s syndrome is caused by a defective gene important for the stability of DNA, which leads to a predisposition to cancer. Affected individuals are short in stature and sensitive to sun exposure, which results in a skin rash across nose and cheeks. They are also at increased risk for diabetes and immune system abnormalities. This is a rare disorder; only a few hundred cases have been reported. Notably, a third of these are from people with Ashkenazi Jewish descent.
Canavan Disease
Canavan disease is caused by mutations in a gene that is important for the normal breakdown of a molecule. This molecule instead accumulates and interferes with the formation of the protective covering of neurons, preventing proper nerve signal transmission. Symptoms include lack of motor development, reduced visual responsiveness, feeding difficulties, abnormal muscle tone, and an abnormally large head. It is most common in people with Ashkenazi Jewish background, where it affects 1 in 6,400 to 13,500, and 1 in 40 is a carrier.
Familial Dysautonomia
Familial dysautonomia is caused by a mutation in a protein important for critical brain cell activity. Symptoms include insensitivity to pain, poor growth, unstable blood pressure and body temperature, inability to produce tears, abnormal sensory perception, episodes of vomiting, and poor bone quality. It is most common in the Ashkenazi Jewish population, where 1 in 30 is a carrier, 1 in 3,600 births is affected by the disease, and more than 600 patients have been identified.
Fanconi Anemia Group C
Fanconi Anemia Group C is caused by a mutation in a protein important for DNA repair, leading to cell death in rapidly dividing cells of the bone marrow, and thus anemia. Reduction of immune cells also occurs and leads to an increased risk for infection and cancer. Buildup of errors in DNA further leads to the development of leukemia and other cancers. Worldwide, 1 in 160,000 people are affected, and it is more common in the Ashkenazi Jewish population, affecting 1 in 32,000.
Gaucher Disease
Gaucher disease is caused by mutations in an enzyme important for the breakdown of a fatty substance that can accumulate within cells and damage the tissues. It primarily affects the spleen, liver, and bone. Symptoms include an enlarged spleen and liver, liver malfunction, bone lesions, neurological complications, swelling of the lymph nodes, and anemia. In the U.S., 1 in 20,000 newborns is affected by the disease, while 1 in 100 is carrier. Worldwide, 1 in 50,000 to 100,000 people are affected by it. It is more common in people of Ashkenazi descent, affecting 1 in 500 to 1,000, and the trait is carried by 1 in 15 people.
Mucolipidosis Type IV
Mucolipidosis type IV is caused by a mutation in a gene important for the transport and removal of substances inside cells. It is characterized by delayed mental and motor development, intellectual disability, limited or absent speech, and vision impairment. It affects 1 in 40,000 people, 70% of which are of Ashkenazi Jewish descent. In the Ashkenazi Jewish population, 1 in 100 is a carrier.
Niemann-Pick Disease Type A/B
Niemann-Pick Disease Type A/B is caused by a mutation in a gene responsible for the production of an enzyme important for the breakdown of a fatty substance in cell. Without this function, the accumulation of this substance leads to cell death. The organs most affected are the brain, spleen, lungs, and liver. Symptoms are more severe and early for type A, and they include an enlarged liver and spleen, loss of mental abilities and motor skills, lung damage, a cherry-red spot in the eye, and failure to thrive. The incidence rate is estimated to be 1 in 250,000, although it is more common in people of Ashkenazi Jewish descent, affecting 1 in 40,000.
Tay-Sachs Disease
Tay-Sachs disease is caused by a mutation in an enzyme responsible for the breakdown of fatty substance in nerve cells. Without this function, the accumulation of these substance leads to cell death. Symptoms include an abnormally strong response to sudden noise (the “startle response”), slowed development, loss of motor skills, blindness, deafness, seizures, mental retardation, and paralysis. It is common in the Ashkenazi Jewish population, where it affects 1 in 3,500 newborns, and 1 in 30 is a carrier. In the general population, 1 in 300 is carrier and 1 in 320,000 newborns is affected.
Dihydrolipamide Dehydrogenase Deficiency & Maple Syrup Urine Disease Type A/B
Dihydrolipamide dehydrogenase deficiency is caused by mutation of DLD, an enzyme involved in the breakdown of amino acids to use for energy. Without this function, the molecules and byproducts accumulate, leading to tissue damage and lactic acid buildup, as well as decreased cellular energy. The brain and liver are primarily affected. Other symptoms include vomiting, abdominal pain, and rapid breathing. It is common in the Ashkenazi Jewish population, in which 1 in 100 is a carrier, and 1 in 35,000 to 48,000 is affected.
Maple Syrup Urine Disease can also be caused by a mutation in DLD, and some symptoms are similar to DLD deficiency. Brain swelling can lead to severe brain damage. Additionally, it is characterized by urine with an odor similar to maple syrup when the person goes into metabolic crisis. This disease affects 1 in 185,000 newborns. In the Mennonite population it affects 1 in 380 newborns.
Familial Hyperinsulinism (FIH)
Familial hyperinsulinism is caused by mutation in genes that regulate secretion of insulin, a hormone which removes glucose from the bloodstream. Those mutations result in insulin being over-secreted, which leads to the rapid depletion of glucose. Low levels of glucose leads to hypoglycemia. Common symptoms include lethargy, irritability, and feeding difficulty. Constant low blood sugar also poses an increased risk for seizures, brain damage, intellectual disabilities, and breathing issues. It is common in the Ashkenazi Jewish population, where 1 in 68 is a carrier, and 1 in 7,800 is affected. In the European population, the incidence is estimated to be 1 in 50,000; and some populations in Finland and Saudi Arabia have an incidence of approximately 1 in 2,500.
Glycogen Storage Disease Type Ia
Glycogen storage disease type 1a is caused by a mutation in a gene that is important for the breakdown of glycogen into glucose for the body to use as energy. Without this function, glycogen builds up in the liver cells, causing the liver to enlarge and the abdomen to appear large. Other symptoms include poor growth and low blood sugar. The incidence rate is about 1 in 100,000.
Joubert Syndrome 2
Joubert syndrome 2 is caused by a mutation in a gene important for cell structure. This results in disruption of chemical signaling in the brain. Symptoms include brain malformations, delayed development, intellectual disability, abnormal eye movements, abnormal breathing, feeding problems, and decreased muscle tone. Some may also be polydactyly. It is most common in the Ashkenazi Jewish population, where 1 in 34,000 affected and 1 in 92 is carrier.
Nemaline Myopathy
Nemaline myopathy is caused by mutations in genes important for the structure of skeletal muscle that allows for contraction. Symptoms include muscle weakness, most severe in the face and neck, leading to difficulty swallowing and breathing. It is common in the Amish population, where 1 in 500 is affected; as well as in the Ashkenazi Jewish population, where 1 in 50,000 is affected and 1 in 100 is a carrier.
Usher Syndrome Type IF
Usher syndrome type 1F is caused by a mutation in a gene important for the development and function of cells in the inner ear and retina. Symptoms include loss of hearing at birth, balance problems, and progressive degeneration of the retina which leads to night blindness and loss of peripheral vision. It is common in the Ashkenazi Jewish population, where 1 in 31,000 affected and 1 in 50 is a carrier.
Usher Syndrome Type III
Usher syndrome type III is caused by a mutation in a gene important for the development and function of cells in the inner ear and retina. Symptoms develop during puberty, and include gradual loss of hearing and progressive degeneration of the retina, which leads to night blindness and loss of peripheral vision. It is common in the Ashkenazi Jewish population, where 1 in 100,000 are affected.
Walker-Warburg Syndrome
Walker-Warburg syndrome is caused by mutations in genes that are important for the stabilization of muscle cells and migration of neurons during early development. Impaired neuron migration affects the development of the brain and eyes. Without stabilization, muscle fibers become damaged with repeated contraction, leading to progressive weakness. This syndrome is estimated to affect 1 in 60,500 newborns worldwide. In the Ashkenazi Jewish population, 1 in 120 is a carrier.
3-Hydroxyl-CoA Dehydrogenase Deficiency
3-Hydroxyl-CoA dehydrogenase deficiency is caused by a mutation in a gene important for the metabolism of fats, leading to their build up in tissues that can damage organs such as the heart, liver, and muscles. Symptoms include lethargy, low blood sugar, high levels of insulin, poor appetite, vomiting, and diarrhea. Those affected are at risk for serious complications such as seizures, heart and breathing problems, coma, and sudden death (SIDS in infants). The incidence rate is unknown.
Glycogen Storage Disease Type II
Glycogen storage disease type II is caused by a mutation in a gene that is important for the breakdown of glycogen into glucose for the body to use as energy. Without this function, glycogen builds up in muscle cells, causing them to become weak. Other symptoms include an enlarged liver, heart defects, and poor growth that can end in failure to thrive. The incidence rate is estimate to be 1 in 40,000.
Myotonic Dystrophy Type 1
Myotrophic dystrophy type 1 is caused by a mutation in a gene important for the proper function of cells in the heart, brain, and skeletal muscles. Symptoms include muscle weakness and wasting and prolonged muscle contraction, particularly affecting the lower legs, hands, neck, and face. Those affected experience slurred speech or locking of the jaw, cataracts, and an abnormal heartbeat. Symptoms are apparent at birth, and cause delayed development and intellectual disability. In the U.S., 30,000 people are affected; worldwide, 1 in 8,000 is affected.
Myotonic Dystrophy Type 2
Myotonic dystrophy is caused by a mutation in a gene important for the proper function of skeletal muscles. Symptoms include muscle weakness and wasting and prolonged muscle contraction, particularly affecting muscles around the shoulders and pelvis. Those affected also experience diabetic changes, cataracts, and heartbeat irregularity. In the U.S., 30,000 people are affected; worldwide, 1 in 8,000 is affected.
Duchenne/Becker Muscular Dystrophy
Duchenne and Becker Muscular Dystrophy (DMD, BMD) are two specific types of muscular dystrophy that primarily affect the skeletal muscles. DMD and BMD have similar symptoms and are caused by different mutations in the DMD gene, which facilitates formation of a protein that stabilizes muscle fibers. The mutation leads to a loss of function in the protein, thereby resulting in the heart and muscle weakness that characterize this condition. These two forms are commonly observed in boys, though it can also affect girls in rare cases. Those affected by either DMD or BMD experience muscle weakness in the arms, legs, and trunk starting from early childhood. Cardiomyopathy is also a common condition associated with BMD/DMD. The incidence rate is estimated to be about 1 in 3,500 to 5,000 newborns.