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Kevin: back to the beach, enjoying life again!
Cory: his Cerebral Palsy doesn't stop him from enjoying life
 Introduction
The Mission of the Center for Neuromuscular Disorders, at The Division of Pediatric Orthopaedic Surgery of the Children’s Hospital of New York Presbyterian, is to provide comprehensive musculoskeletal care to children with various types of neuromuscular disorders including cerebral palsy, the muscular dystrophies, myelomeningocele and various congenital syndromes which affect the musculoskeletal system in children.
Children in our center, here in the City of New York, often come in with problems related to increased or decreased muscle tone, hip dislocation, clubfoot, scoliosis or contractures of the muscles around the body.
If left untreated, muscles that have too much tone or tightness or too little tone can interfere with function, cause pain and result in problems in the skeleton such as scoliosis, hip subluxation or dislocation. Our multidisciplinary group takes a proactive but conservative approach to the management of these children in an attempt to decrease the problems that often result if the abnormal tone is left untreated.
Botulinum toxin is an important option for conservatively managing these kids, and our group has a special interest in the use of Botox to improve quality of life and prevent disability in these kids. Special bracing is often required to maintain the gains made with physical therapy and or Botox, and we feel fortunate to be associated with a team of Pediatric Orthotists with special expertise in this area. While surgery sometimes has a role, we see surgery- particularly in young children- as only one of many options in the care of children with neuromuscular disorders.
We perform a wide array of clinical research examining outcomes, quality of life and treatment options for children with neuromuscular disorders.
What is a neuromuscular disease?
A neuromuscular disease is characterized by impairment of the central or the peripheral nervous system. The central nervous system includes the brain and spinal cord. The peripheral nervous system includes muscles, the nerve-muscle (neuromuscular) junction, peripheral nerves in the limbs and the motor-nerve cells in the spinal cord.
Common symptoms for neuromuscular diseases include increased or decreased tone, loss of muscle bulk, weakness, muscle twitching, cramping, numbness and tingling. Patients with problems with the nerve-muscle junction may experience droopy eyelids, double vision, and weakness that worsens with activity. Some neuromuscular disorders can also cause difficult swallowing and may result in difficulty in breathing. Children with neuromuscular diseases often have delayed development.
The different types of neuromuscular diseases
Neuromuscular disorders include a large group of diseases affecting any part of the central and peripheral nervous system and the muscle.
 Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) causes the muscles to weaken and waste away (atrophy) due to degeneration of nerve cells in the spinal cord (motor neurons). Under normal conditions, the brain sends signals to motor neurons, which than are received and sent to muscle cells. When these motor neurons malfunction, the muscles deteriorate. Intelligence and sensory nerves are not affected.
SMA is inherited as an autosomal recessive trait. This means a person needs to get the defective gene from both parents in order to be affected. Approximately 4 out of 100,000 people are affected.
Three different types of SMA in childhood can be distinguished by the age of onset and the severity of the condition.
SMA type I, severe infantile SMA or Werdnig-Hoffmann disease, is the most severe form. Usually diagnosed in the first 6 months of life, the child is unable to roll or sit unsupported. Infants are born floppy with weak, thin muscles eventually causing feeding and breathing problems. Their lifespan usually does not surpass 18 months of age.
SMA type II patients have symptoms less severe during early infancy, however, they become progressively weaker with time. Their life span rarely exceeds 2 to 3 years.
SMA type III is the least severe form of the disease. Symptoms such as weakness in the shoulder muscles and proximal leg muscles may not appear until between 2 and 17 years of age. Atrophy and weakness of proximal limb muscles, primarily in the legs, is followed by distal involvement. Usually the cases are diagnosed as limb-girdle muscular dystrophy until they are studied fully. Twitchings (fasciculations) are an important differentiating sign. Muscular biopsy and electromyography show the true nature of the process as a lower motor neuron disease. Pulmonary dysfunction is often a cause of morbidity in these patients Weakness in the muscles is progressive and eventually become more severe; however, children with type III disease can survive well into early adulthood.
Muscular Dystrophies
Muscular dystrophy classifies a group of genetically inherited disorders resulting from defects in a number of genes required for normal muscle function. Muscle strength and bulk gradually decline. Muscular dystrophies are generally recognized and classifies into 9 different categories.
Duchenne Muscular Dystrophy (DMD) (Also known as Pseudohypertrophic)
Duchenne Muscular Dystrophy is classified with having the most severe clinical symptoms. DMD is a disease resulting from inheritance of an X-linked recessive gene, causing an absence of dystrophin, a protein that helps keep muscles in tact. DMD primarily affects boys, who inherit the disease through their mothers. Women can be carriers of DMD but usually exhibit no symptoms. The onset of DMD typically occurs between the ages of 2 to 6 years of age. Symptoms include general weakness and muscle wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are also often enlarged. Eventually, DMD afftects all voluntary muscles, and the heart and breathing muscles. Patients rarely live beyond their early 30s.
Becker Muscular Dystrophy (BMD)
Becker Muscular Dystrophy, one of the nine types of muscular dystrophies, is a degenerative disease primarily affecting voluntary muscles. BMD is a disease resulting from inheritance of an X-linked recessive gene. As a result there is an insufficient production of dystrophin, a protein that helps keep muscles intact. BMD primarily affects boys and men, who inherit the disease through their mothers. Women can be carriers but usually exhibit no symptoms. Usually symptoms show at adolescence or adulthood. BMD is similar to Duchenne muscular dystrophy but often much less severe. Patients usually show generalized weakness and wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged and there can also be significant heart involvement. The disease progresses slowly and with variability, but can affect all voluntary muscles. Most patients with BMD can survive well into mid to late adulthood.
Emery-Dreifuss Muscular Dystrophy (EDMD)
Emery-Dreifuss Muscular Dystrophy (EDMD) is a degenerative disease primarily affecting voluntary muscles. EDMD can be X-linked recessive, primarily affecting males, who inherit the disease through their mothers. Another type of inheritance is autosomal dominant. This means the disease can be inherited through either the mother or the father. An autosomal recessive types occurs when a faulty gene is inherited from each parent. Mutations occur in genes that produce emerin, lamin A or lamin C, all which are proteins in the membrane that surround the nucleus of each muscle cell. Symptoms usually onset by age 10 and include weakness and wasting of shoulder, upper arm and calf muscles. EDMD patients also suffer from joint stiffening and fainting (because of cardiac abnormalities). Cardiac complications are common and sometimes require a pacemaker.
Limb-Girdle Muscular Dystrophy (LGMD)
Limb-Girdle Muscular Dystrophy (LGMD) is a degenerative disease primarily affecting the voluntary muscles. LGMD can be inherited from just one parent (autosomal dominant). Other types are autosomal recessive, meaning the disease is brought on when a faulty gene is inherited from each parent. LGMD results in a mutation in any of at least 15 different genes that affect proteins necessary for muscle function. Usually symptoms are brought on anywhere from childhood to adulthood. The disease usually progresses slowly with weakness and wasting first affecting the muscles around the shoulders and hips. Cardiopulmonary complications sometimes occur in later stages of the disease.
Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral Muscular Dystrophy (FSHD), also known as Landouzy-Dejerine, is degenerative disease primarily affecting voluntary muscles caused by a missing piece of DNA on chromosome 4. FSHD may be inherited through either the father or the mother (autosomal dominant). Although diagnosed by age 20, the disease progresses slowly with some periods of rapid deterioration and may span many decades. Weakness and wasting of the muscles around the eyes and mouth, and of the shoulders, upper arms and lower legs are common initially; however, as the disease progresses, weakness of abdominal muscles and sometimes hip muscles is common.
Myotonic Dystrophy (MMD)
Myotonic Dystrophy (MMD), also known as Steinert's Disease, is a degenerative disease primarily affecting voluntary muscles, and is caused by a repeated section of DNA on either chromosome 19 or chromosome 3. MMD is autosomal dominant and may be inherited through either the father or mother. Congenital (existing at birth) myotonic dystrophy is the more severe form. The more common form may begin in teen or adult years. The progression of the disease is usually slow, sometimes spanning 50 to 60 years. Generalized weakness and muscle wasting first affecting the face, lower legs, forearmd, hands and neck, with delayed relaxation of muscles after contraction is common. Other symptoms involve the gastrointestinal system, vision, heart or respiration. Learning disabilities also occur in some cases.
Oculopharyngeal Muscular Dystrophy (OPMD)
Onset: Early adulthood to middle age.
Distal Muscular Dystrophy (DD)
Onset: 40 to 60 years of age.
Congenital Muscular Dystrophy (CMD)
Congenital Muscular Dystrophy (CMD) is a degenerative disease primarily affecting voluntary muscles resulting from genetic mutations affecting some of the proteins necessary for muscles and sometimes for the eyes and or brain. The disease is inherited through both parents. Brought on at or near birth, CMD varies with type. Many are slowly progressive; some shorten life span. Common symptoms include generalized muscle weakness with possible joint stiffness or looseness. Depending on the type, CMD may involve spinal curvature, respiratory insufficiency, mental retardation or learning disabilities, eye defects or seizures.
Motor Neuron Diseases
Motor Neuron Diseases (MND) classify a group of diseases affecting the motor neurons in the brain and spinal cord. Motor neurons are efferent neurons that originate in the spinal cord and synapse with muscles fibers to facilitate muscles contraction and with muscles spindles to modify one's own sensitivity. Degeneration of the motor neurons leads to weakness and wasting of muscles (atrophy) in the arms and legs initially. Some MNDs lead to weakness and wasting in the muscles supplying the face and throat, causing problems with speech and difficulty chewing and swallowing. Intellect remains unaffected. Like the muscular dystrophies, motor neuron diseases is generally a steadily progressive disease, however, the rate of progression varies greatly from one person to another.
Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig's Disease
Onset: Adulthood.
Infantile Spinal Muscular Atrophy (SMA type 1)
Intermediate Spinal Muscular Atrophy (SMA type 2)
Juvenile Spinal Muscular Atrophy (SMA type 3)
Spinal Bulbar Muscular Atrophy (SBMA) also known as Kennedy's Disease and X-linked SBMA
Onset: Adulthood.
Adult Spinal Muscular Atrophy (SMA)
Onset: adulthood.
Inflammatory Myopathies
Inflammatory myopathies are a group of muscle diseases that cause inflammation and degeneration of the skeletal muscle tissues. The cause of these diseases is unknown, however, they are thought to be autoimmune disorders (disorders that cause the body's tissues to be attacked by its own immune system.) For people with inflammatory myopathies, inflammatory cells surround, invade and destroy normal muscle fibers as though they were defective or foreign to the body. This eventually results in noticeable muscle weakness. This muscle weakness usually affects both sides of the body and may develop over weeks, months or even years. Inflammatory myopathies affect women nearly twice as often as they affect men.
Dermatomyositis (PM/DM)
Dermatomyositis is one of a group of muscle diseases that involve inflammation of the muscles or associated tissues; the inflammatory cells of the immune system attack the blood vessels that supply muscles and skin. The cause of Dermatomyositis is unclear, however, it is suspected that viruses or exposure to certain drugs might trigger the misdirected immune response. The gradual progression of the disease usually begins to onset from childhood to adulthood. Distinctive reddish or purplish rashes are common symptoms as well as rough, scaly skin. Patients also often have hard, painful calcium nodules under the skin. Weakening of the muscles of the hips, thighs, upper arms, top part of the back, shoulders and muscles that move the neck also occur. Heart and respiratory problems are not uncommon. Immunosuppressant medications often effectively control symptoms.
Polymyositis (PM)
Polymyositis, like Dermatomyositis, is not a genetic disease, though a genetic predisposition may exist. Also one of a group of muscles diseases that involve inflammation of the muscles or associated tissues, polymyositis has no clear cause. Researchers suspect viruses or exposure to certain drugs might trigger the misdirected immune system. The disease can trigger anywhere from childhood to early adulthood and is more commonly found in females than males. Symptoms include weakness of the muscles of the hips, thighs, upper arms, top part of the back, shoulders and muscles that move the neck. Respiratory complications are also not uncommon. Immunosupressive drugs often help to control symptoms.
Inclusion Body Myositis (IBM)
Onset: after age 50.
Diseases of the Neuromuscular Junction
Diseases of the neuromuscular junction are caused when the neuromuscular junction, the space where the nerve signal is passed from nerve to muscle, does not work correctly.
Myasthenia Gravis (MG)
Myasthenia Gravis is an autoimmune disease, a disease in which the immune system attacks the body's own tissues. This attack occurs at the junction between the nerve and the muscles and targets the acetylcholine receptor, the part of a muscle cell that receives signals from a nerve cell. The attack can also occur on muscle-specific kinase, a protein that helps to organize acetylcholine receptors on the muscle cell. The cause of myasthenia gravis is unclear, however, researchers suspect viruses or bacteria might trigger the autoimmune response. The thymus gland also sometimes plays a role in the disease. The disease can appear anywhere from childhood to adulthood and is 1.5 times more common in women than in men. The disease usually progresses to maximum severity within 1 to 3 years of onset, however, with proper treatment people can remain physically active. Symptoms often include fatigue and weakness of voluntary muscles, partial paralysis of eye movement, double vision, and droopy eyelids. Weakness and fatigue in the neck and jaws often occurs and patients usually have problems with chewing, swallowing and holding up their head.
Lambert-Eaton Syndrome (LES)
Onset: adulthood to middle age.
Congenital Myasthenic Syndrome (CMS)
Congenital Myasthenic Syndrome (CMS) is one of the many types of inherited diseases that affect the function of processes at the junction of nerve and muscle cells. CMS is caused by defects in genes that are necessary to make proteins of the neuromuscular junction. Usually diagnosed at or near birth, CMS is autosomal dominant, meaning it can be inherited through either parent; CMS is also autosomal recessive, when a faulty gene is inherited from each parent. Both the symptoms and progression of the disease vary depending on the type of CMS.
Myopathies Due to Endocrine Abnormalities
Malfunctioning glands producing either too much or too little hormones can cause a myopathy. Carried by the blood, hormones are chemical messengers that regulate muscle activity. Problems hormone production can therefore lead to muscle weakness.
Hyperthyroid (Endocrine) Myopathy (HYPTM)
Hyperthyroid Myopathy is an autoimmune disease and occurs when the immune system attacks the body's own tissues; in this case it attacks the thyroid gland. This causes an overproduction of the hormone thyroxine. Although the cause of the disease is unclear, researchers suspect viruses or bacteria might trigger the autoimmune response and patients may begin to show symptoms anywhere from childhood to adulthood. These symptoms include muscle weakness, some muscle wasting in the hips and shoulder, problems with controlling eyes and eye lids and possible periodic paralysis. Fortunately, the progression of the disease can be almost completely alleviated by restoring normal thyroxine levels. This is done through surgery or medication.
Hypothyroid (Endocrine) Myopathy (HYPOTM)
Hypothyroid Myopathy is also an autoimmune disease; however, in this case it attacks the thyroid gland causing an underproduction of the hormone thyroxine. It too is brought on anywhere from childhood to adulthood and the cause is unclear. Symptoms include weakness of muscles (specifically of the arms and legs), general stiffness and cramps. HYPOTM can also cause rhabdomyolysis, or severe breakdown of muscle tissue.
Diseases of the Peripheral Nerve
The peripheral nervous system is composed of all of the nerves not located in the central nervous system; these are nerves in the face, arms, legs, torso and some cranial nerves. Nerves have the extremely important role of providing communication between the brain and muscles, skin, internal organs and blood vessels. If they are damaged, this communication is blocked. Consequently, this miscommunication causes symptoms such as pain or numbness.
Charcot-Marie-Tooth Disease (CMT) is now included in a group of disorders known as Hereditary Motor and Sensory Neuropathy (HMSN) or Peroneal Muscular Atrophy (PMA)
Charcot-Marie-Tooth Disease (CMT) is a neurological disorder that causes damages to the peripheral nerves. CMT is caused by defects in the genes for proteins found in axons, fibers that carry electrical signals between the brain and spinal cord and the rest of the body. Defects in genes for proteins found in myelin, a coating on axons that insulates and nourishes them, can also cause CMT. Usually diagnosed anywhere from birth to adulthood, common symptoms include muscle weakness and wasting as well as some loss of sensation in the feet, lower legs, hands and forearms. CMT patients often have contractures (stiffened joints) and sometimes develop scoliosis. The disease usually progresses slowly and is inheritable through a faulty gene contributed by each parent (autosomal dominant). CMT can also be X-linked, meaning it is inheritable through a gene on the X chromosome contributed by either parent.
Dejerine-Sottas Disease (DS) (Also known as CMT Type 3 or Progressive Hypertrophic Interstitial Neuropathy)
Dejerine-Sottas disease is an inherited neurological disorder that progressively affects mobility. Peripheral nerves become enlarged or thickened leading to muscle weakness. Progress of the disorder is irregular and often accompanied by pain, weakness, numbness, and a tingling, prickling or burning sensation in the legs. Many people with Dejerine-Sottas disease continue to lead active lives. Most neurologists now consider this disorder to be one of 5 types of hereditary motor sensory neuropathy (HMSN) which simply means genetically transmitted disorder of the nerves associated with movement. Dejerine-Sottas disease is one of several that comprise Type III and in which the protective sheath around the long nerves breaks down (demyelination) for unknown reasons exposing and endangering the nerve. The nerves are enlarged due to an accumulation of connective tissue that may present in the form of "onion-bulbs".
Friedreich's Ataxia (FA)
Friedreich's Ataxia (FA) is a neurological disorder caused by defects in the gene that carries instructions for frataxin, a protein found in cellular structures called mitochondria. This results in diminished energy production in cells, including those of the nervous system and heart. Inheritance is brought on through a faulty gene contributed by each parent. Symptoms include ataxia (loss of balance and coordination), difficulty with speech and swallowing, muscle spasms, loss of sensation, skeletal and cardiac abnormalities, and possible diabetes or glucose intolerance. Typically FA is diagnosed between 10 and 15 years old.
Other Myopathies
Myopathies classify a group of diseases that affect skeletal muscles, muscles connected to the bones. Almost all myopathies cause weakening and gradual wasting of the muscles, especially those closest to the center of the body. Myopathies can be caused by inherited genetic defects (i.e., muscular dystrophies), and endocrine, inflammatory (i.e., polymyositis), and metabolic disorders. Some myopathies develop at an early age; others develop later in life.
Myotonia Congenita (MC) (Two forms: Thomsen's and Becker's Disease)
Myotonia Congenita is an autosomal recessive genetic, neuromuscular disorder characterized by the slow relaxation of the muscles. The disorder is caused by mutations in a gene that carries instructions for a chloride channel, a pore in the muscle cell surface that regulates the movement of chloride molecules. Symptoms may include delayed muscle relaxation and muscle stiffness, which usually are provoked by sudden movements after rest. The disease is diagnosed usually anywhere from early to late childhood.
Paramyotonia Congenita (PC)
Paramyotonia Congenita is an autosomal dominant genetic, neuromuscular disorder usually diagnosed at or near birth. The disease is caused by mutations in the gene that carries instructions for a sodium channel, a pore in the muscle cell surface that regulates the movement of sodium molecules. PC causes problems with tone and contraction of skeletal muscles; symptoms may include muscle stiffness and weakness (mostly in the face, neck and upper extremities).
Central Core Disease (CCD)
Central Core Disease (CCD) is one of a group of diseases that cause problems with tone and contraction of skeletal muscles. Usually diagnosed at or near birth, CCD patients usually suffer from poor muscle tone and persistent muscle weakness and motor milestones are reached late. Skeletal deformities, including joint dislocation and scoliosis, often occur as well. Autosomal inheritance results in a defective gene that carries instructions for a molecular "gate" that releases calcium from inside muscle cells.
Nemaline Myopathy (NM)
Nemaline Myopathy is a neuromuscular disorder characterized by muscle weakness and the presence of nemaline bodies in the muscle fibers. NM has two forms, one autosomal recessive and one autosomal dominant. Muscle weakness is usually most severe in the face, the neck flexors and the proximal limb muscles. Patients often suffer from respiratory problems and infants commonly have problems with feeding. NM is usually diagnosed by infancy, however, childhood-onset and adult-onset cases have been identified.
Myotubular Myopathy (MTM or MM)
Myotubular Myopathy (MM) characterizes a group of disorders that cause problems with the tone and contraction of skeletal muscles. The most common and congenital form is X-linked, meaning it is carried on the X chromosome and usually affects only boys. This form is caused by defects or deficiencies of myotubularin, a protein thought to promote normal muscle development. Patients usually suffer from severe muscle weakness and hypotonia (lack of muscle tone). This results in a patient's inability to have proper posture and movement. X-linked MM patients also have life-threatening difficulties with feeding and respiration. Anemia and serious liver abnormalities are also not uncommon. The autosomal dominant form onsets anywhere from childhood to adulthood and the autosomal recessive form onsets from infancy to early adulthood. Both autosomal forms cause similar problems to X-linked, but the autosomal dominant form is considered mild, and the autosomal recessive form is considered intermediate. Both types affect the child's ability to attain motor milestones at normal times. In autosomal forms, muscle problems are progressive.
Periodic Paralysis (PP) (Two forms: Hypokalemic-HYPOP- and Hyperkalemic-HYPP)
Periodic Paralysis are rare disorders of the voluntary muscles characterized by episodes of attacks or muscle weakness. Between these attacks, affected muscles most often work normally. There are two forms of PP: Hypokalemic and Hyperkalemic. In hypokalemic, low levels of potassium in the blood interact in an unknown way with genetically caused abnormalities in calcium changes in muscle cells. In hyperkalemic, high levels of potassium in the blood interact in an unknown way with genetically caused abnormalities in sodium channels in muscle cells. Each condition is also sometimes caused by genetic abnormalities in channels for sodium or potassium. Both forms are inherited by a defective gene contributed by one parent (autosomal dominant). Hyperkalemic is diagnosed during childhood, whereas hypokalemic can onset anywhere form childhood to adulthood. In hyperkalemic, the frequency of attacks declines after middle age. The number of attacks with hypokalemic patients usually varies, but severe attacks cause nearly full-blown paralysis.
Metabolic Diseases of the Muscle
Each of the metabolic disorders of the muscle are caused by different genetic defects that impair the body's ability to process chemical reactions that occur within cells during normal functioning. Under normal conditions, fuel molecules broken down from the food, and then are broken down further inside of each cell before they can be used by the mitochondria of the cell to produce ATP. The metabolic diseases of the muscle results from problems that occur when certain fuel molecules are processed before they enter the mitochondria, or by the cell's inability to get fuel molecules into the mitochondria. ATP drives all muscle activity in the body, and when ATP levels are low, muscle weakness, pain or cramps may occur. Metabolic diseases that are diagnosed at infancy are most severe; however, those that begin in childhood or adulthood tend to be less severe, and changes in lifestyle or diet can help these mild forms.
Phosphorylase Deficiency (MPD or PYGM) (Also known as McArdle's Disease)
Phosphorylase Deficiency (MPD) is an autosomal recessive muscle disease that interferes with the processing of carbohydrates to draw energy from food. More specifically, a genetic defect in the phosphorylase enzyme results in the cell's inability to breakdown glycogen. Patients are diagnosed anywhere from childhood to adulthood and suffer from symptoms including cramps, muscle pain, muscle weakness and exercise intolerance.
Acid Maltose Deficiency (AMD) (Also known as Pompe's Disease)
Acid Maltose Deficiency (AMD) is caused by complete or partial deficiency of the lysosomal enzyme, alpha-glucoidase, the enzyme necessary for the breakdown and conversion of glycogen into glucose. Absence of alpha-glucosidase results in accumulation of a thick sticky substance in the lysosomes (sacs within the muscle cells). Eventually this leads to severe muscle degradation. AMD affects the heart, skeletal and respiratory muscles of the patient. This autosomal recessive disorder can be recognized in patients from infancy to adulthood. AMD is slowly progressive and less severe in childhood and adult-onset forms; the infantile form often leads to death by two years of age.
Phosphofrucokinase Deficiency (PFKM) (Also known as Tarui's Disease)
Phosphofructokinase Deficiency (PFKM) is one of the group of muscle disease that interferes with the processing of carbohydrates to draw energy from food. The cause of PFKM is thought to be a result of a genetic defect in the phosphofructokinase enzyme, which affects the storage and breakdown of glucose. Onset is anywhere from childhood to adulthood and is inherited by the contribution of a defective gene from each parent (autosomal recessive). Symptoms for PFKM include exercise intolerance, pain, cramping and occasionally myoglobinuria (rust-colored urine indicting breakdown of muscle tissue).
Debrancher Enzyme Deficiency (DBD) (Also known as Cori's or Forbes Disease)
Debrancher Enzyme Deficiency (DBD) is an autosomal recessive disorder caused by a genetic defect in the debrancher enzyme, which affects the breakdown of glycogen, the stored form of glucose(sugar). The progression of the disease is slow, except in the severe infantile form. Symptoms are generalized weakness and muscle wasting, enlarged liver in infancy, and episodes of low blood sugar.
Mitochondrial Myopathy (MITO)
Mitochondrial Myopathy (MITO) is a group of diseases affecting the mitochondria, small structures located outside of the nucleus in the cytoplasm that are responsible for energy production in cells. Mitochondrial Myopathy is a group comprised of Kearns-Sayre Syndrome, Leigh's syndrome, Mitochondrial DNA Depletion Syndrome (MDS), Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes (MELAS), Myoclonus Epilespsy with Ragged Red Fibers (MERRF), Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE), Neuropathy, Ataxia and Retinitis Pigmentosa (NARP), and Progressive External Ophthalmoplegia (PEO). These disorders are caused by defects in genes that produce proteins that process food into energy inside cells. The affected protein determines which of the many mitochondrial diseases are present. The onset of most mitochondrial myopathies is before the age of 20 and they often begin with muscle weakness. During physical activity muscles may become easily fatigued or weak. Besides fatigue and muscle weakness, symptoms also include nausea, vomiting, headache, seizures, stroke-like episodes, droopy eyelids, blindness, deafness, heart failure and heart rhythm disturbances. Progression varies according to the specific disease as well as inheritance.
Carnitine Deficiency (CD)
Carnitine Deficiency (CD) is one of a group of muscle diseases that interferes with the processing of fats to draw energy from food. CD is caused by a defect in a gene for protein that brings carnitine into the cell. The slowly progressive disease is autosomal recessive, caused by the contribution of a defective gene from each parent. The onset of CD is usually at early childhood. Symptoms include cardiac disease, muscle weakness in the hips, shoulders and upper arms and legs. Neck and jaw muscles may also be weak.
Carnitine Palmityl Transferase Deficiency (CPT)
Onset: Young adulthood.
Phosphoglycerate Kinase Deficiency (PGK)
Phosphoglycerate Kinase Deficiency (PGK) is an X-linked recessive muscle disease that interferes with the processing of carbohydrates to draw energy from food. PGK is caused by a genetic defect in the phosphoglycerate kinase enzyme, which affects the processing of carbohydrates for fuel. Diagnosis of PGK usually occurs anywhere from infancy to early adulthood. Muscle symptoms are slowly progressive and may include weakness, exercise intolerance, muscle cramping and episodes of myoglubinuria (rust-colored urine indicating the breakdown of muscle tissue). PGK also may cause anemia, enlargement of the spleen, mental retardation and epilepsy.
Phosphoglycerate Mutase Deficiency (PGAM or PGAMM)
Onset: Early adulthood.
Lactate Dehydrogenase Deficiency (LDHA)
Onset: early adulthood.
Myoadenylate Deaminase Deficiency (MAD)
Onset: early adulthood to middle age.
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