AUTOSOMAL RECESSIVE JEWISH GENETIC DISEASES
Bloom syndrome is an inherited disorder characterized by short stature, a skin rash that develops after exposure to the sun, and a greatly increased risk of cancer. Individuals with Bloom syndrome can have learning disabilities, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), and mild immune system abnormalities leading to recurrent infections of the upper respiratory tract, ears, and lungs during infancy.
Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. Neonatal/infantile Canavan disease is the most common and most severe form of the condition. Affected infants appear normal for the first few months of life, but by 3 to 5 months of age, they develop a large head, poor muscle tone, motor delays and a progressive loss of function. The mild/juvenile form of Canavan disease is less common. Affected individuals have mildly delayed development of speech and motor skills starting in childhood. These delays may be so mild and nonspecific that they are never recognized as being caused by Canavan disease.
Cystic fibrosis (CF) is an inherited disease characterized by the buildup of thick, sticky mucus that can damage many of the body’s organs, primarily the lungs and digestive tract. The disorder’s most common signs and symptoms include failure to gain weight in infancy, chronic cough and/or upper respiratory infections, chronic diarrhea or gastrointestinal problems and elevated sweat electrolyte levels. More than 95% of males with CF have reduced fertility. Females may have decreased fertility as well. The features of the disorder and their severity vary among affected individuals and with different mutations.
Dihydrolipoamide dehydrogenase deficiency
Dihydrolipoamide dehydrogenase deficiency (DLD) is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals. A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy).
Familial dysautonomia (FD) is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, difficulty maintaining body temperature and decreased sensitivity to pain.
Familial hyperinsulinism (FH)
Familial hyperinsulinism (FH) is an inherited disorder in which the pancreas produces too much insulin, which results in low blood sugar (hypoglycemia). This can vary from mild to severe. Hypoglycemia can present in the immediate newborn period through the first year of life. If untreated, the most common symptoms are seizures, poor muscle tone, poor feeding and sleep disorders.
Fanconi anemia is a condition that affects many parts of the body. People with this condition may have bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers. Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).
Gaucher disease is an inherited disorder that affects many of the body’s organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Type 1 Gaucher disease is the most common form of this condition and is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), and bone abnormalities such as bone pain, fractures, and arthritis. Effective treatment is available for Type 1 Gaucher disease.
Glycogen storage disease type I
Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body’s cells. This buildup occurs because the body can’t break down glycogen into glucose, the sugar the body needs to produce energy. Therefore, affected individuals cannot maintain their blood glucose levels and develop hypoglycemia. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally. Signs and symptoms of this condition typically appear around the age of 3 or 4 months, when babies start to sleep through the night and do not eat as frequently as newborns. Affected infants may have low blood sugar (hypoglycemia), which can lead to seizures, a buildup of lactic acid in the body (lactic acidosis), high blood levels of a waste product called uric acid (hyperuricemia), and excess amounts of fats in the blood (hyperlipidemia). Treatment involves providing the individual with a steady glucose supply throughout the day and night.
Joubert syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family. The hallmark feature of Joubert syndrome is a structural malformation of the mid- and hind-brain called the molar tooth sign, which can be seen on brain imaging studies such as magnetic resonance imaging (MRI). Most infants with Joubert syndrome have weak muscle tone (hypotonia) in infancy, which evolves into difficulty coordinating movements (ataxia) in early childhood. Other characteristic features of the condition include episodes of unusually fast or slow breathing in infancy, abnormal eye movements, developmental delays and kidney abnormalities.
Maple syrup urine disease
Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants’ urine and is also characterized by poor feeding, vomiting, lack of energy (lethargy), and developmental delay. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other health problems if not treated. Treatment involves strict dietary control of a low protein diet.
Mucolipidosis type IV
Mucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV. Approximately 95 percent of individuals with this condition have the severe form with delayed development of mental and motor skills (psychomotor delay) which usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements.
Nemaline myopathy is a disorder that primarily affects skeletal muscles. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). In severe cases, the muscles used for breathing are affected and life-threatening breathing difficulties can occur.
Niemann-Pick disease type A
Niemann-Pick disease is a condition that affects many body systems. Infants with Niemann-Pick disease type A usually appear normal at birth, but by 3 months of age develop an enlarged liver and spleen (hepatosplenomegaly), fail to gain weight and grow at the expected rate (failure to thrive), and begin to progressively lose cognitive and motor skills. Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination.
Spinal muscular atrophy
Spinal muscular atrophy is a genetic disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and in the brainstem (the part of the brain that is connected to the spinal cord). The motor neurons are responsible for supplying electrical and chemical signals to the muscle cells. Without proper signals, muscle cells do not function properly and thus atrophy.
There are four forms of spinal muscular atrophy distinguished by age of onset of symptoms and the severity of muscle weakness. Generally, the earlier symptoms arise, the more severe the disease. Type I spinal muscular atrophy (also called Werdnig-Hoffman disease) is the most severe form of the disorder and is evident before 6 months of age, whereas signs and symptoms of Type IV often don’t occur until after age 30.
Tay-Sachs disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder.
Usher syndrome is a condition characterized by hearing loss or deafness and progressive vision loss due to retinitis pigmentosa. Researchers have identified three major types of Usher syndrome, designated as types I, II, and III, distinguished by their severity and the age when signs and symptoms appear. Individuals with Usher syndrome type I are typically born completely deaf or lose most of their hearing within the first year of life and progressive vision loss becomes apparent in childhood. This type of Usher syndrome also includes problems with the inner ear that affect balance. Individuals with Usher syndrome type III are usually born with normal hearing; hearing loss typically begins during late childhood or adolescence, after the development of speech, and progresses over time. Vision loss begins to develop in adolescence.
Walker-Warburg syndrome is a severe, inherited disorder that affects development of the muscles, brain, and eyes, and the most severe of a group of genetic conditions known as congenital muscular dystrophies. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Walker-Warburg syndrome affects the skeletal muscles, and affected babies have weak muscle tone (hypotonia) and are sometimes described as “floppy.” Walker-Warburg syndrome also affects the brain and may also have a buildup of fluid in the brain (hydrocephalus). Eye abnormalities are also characteristic of Walker-Warburg syndrome.