Myophosphorylase deficiency type V or McArdle disease (MPD5): This autosomal recessive (chromosome 11q13) glycogen storage disease is one of the most common muscle glycogenoses and typically presents in adolescence or its late-onset form (up to the 8th decade) with exercise intolerance, severe myalgia, myoglobinuria (25%), and cramps in exercising muscle due to contractures, relieved by rest. Often a “second wind” phenomenon (improvement after rest) is found. In addition, fixed, asymmetric proximal limb and bulbar weakness can be found particularly at an advanced age. The resting serum CK levels are usually increased. EMG confirms the myopathic process, the forearm ischemic exercise test is positive (no increase in serum lactate) in complete myophosphorylase deficiency and muscle biopsy (residual myophosphorylase activity less than 12 mmol/min/g) is diagnostic. Analysis of the patient’s DNA from leucocytes can be used for diagnosis. Oral fructose and high protein diet may sometimes be helpful. This form is indistinguishable from phosphofructokinase deficiency type VII or Tarui disease (PFKD) which is characterized by lifelong intolerance to vigorous exercise, often accompanied by cramps and nausea that are relieved by rest.
Myoadenylate deaminase deficiency: Primary myoadenylate deaminase deficiency is the most common of the known enzyme deficits of muscle. The primary type seems to be inherited in an autosomal recessive pattern. The deficiency is usually not symptomatic until adult or middle age, when symptoms of postexertional aches, cramps, weakness, and skeletal muscle dysfunction develop. A presumptive diagnosis can usually be made by an ischemic forearm exercise test, which shows abnormally high plasma ammonia, despite a normal rise in lactate. Despite the absence of more than 99% of normal adenylate deaminase activity, the muscle biopsy may show no anatomic pathology, and other enzymes are at normal levels. Patients suffering from myoadenylate deaminase deficiency do not suffer progressive disease. The heterozygous state is probably asymptomatic, except, on extreme exercise, but may be associated with an increased incidence of malignant hyperthermia susceptibility. MRI spectroscopy shows an increased muscle glycogen content, with a slight and delayed drop of pH during exercise.
Debrancher enzyme deficiency type III or Forbes-Cori disease (DED3): The clinical appearance of this autosomal recessive (chromosome 1p21) myopathy is highly variable. In the adult forms (starting in the 3rd and 4th decade) we differentiate several phenotypes: (1) muscular symptoms in adult years while the liver symptoms start in childhood, (2) muscle weakness starting in adult years long after liver symptoms in childhood have remitted, (3) only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. Rapid fatigue and aching of muscles is a common presentation, occurring at exertion and beginning at an early age. The myopathy can also have different forms: (1) adult onset distal myopathy (distal leg weakness and intrinsic hand muscles); (2) subacute myopathy of the respiratory muscles; (3) severe generalised myopathy; and (4) minimal variant myopathy. Exercise intolerance is uncommon. Rarely, a mild polyneuropathy may be observed. The clinical course is complicated by advanced liver dysfunction and by severe cardiomyopathy. All patients have raised CK concentrations (up to 800 U/l), myogenic and neurogenic (denervation) features with pseudomytonic discharges on EMG, and markedly decreased debrancher enzyme activities in muscle or liver biopsy specimens. Leucocyte glycogen debrancher enzyme assay provides the diagnosis.
Potassium-related periodic paralysis: These disorders are transmitted by autosomal dominant trait and characterized by intermittent episodes of weakness or paralysis, often with normal muscle function between attacks. Potassium levels may vary (hypokalemic, normokalemic or hyperkalemic periodic paralysis.
Hypokalemic periodic paralysis is the most common form. The onset of symptoms ranges from the 2nd - 3rd decades of life. Attacks of moderate to severe weakness often occur at night, episodes can last from hours to days and are precipitated by rest after exercise, cold exposure, excitement, and carbohydrate meals (provocative test). Weakness persists for a time after serum level has been restored. Limbs may be more affected than trunk. Potassium is usually low (seldom normal). There is no associated clinical or EMG myotonia. Acetazolamide is effective in the treatment. Mutations in calcium channel gene (CACNA1S) are responsible for this calcium channel (L-type) disease.
Primary hyperkalemic periodic paralysis: This autosomal dominant disorder usually starts in the 1st decade of life. The episodes of mild to moderate weakness are more frequent but briefer in duration (minutes to hours). Their frequency tends to decline with age. Attacks of weakness occur usually before breakfast and later in the day may be precipitated by rest after exercise, immobility, potassium ingestion, irregular diet, cold exposure, or emotional stress. Weakness starts in the legs, thighs and lower back and spreads to hands, forearms and shoulders. Respiratory muscles are usually spared. Attacks last 15-60 min and recovery can be hastened by mild exercise. After an attack, weakness may persist for several days. Myotonia may occur (clinical or on EMG). Potassium is usually high or may be normal. Provacative test (2 g oral potassium load in a sugar-free liquid repeated every 2 h for 4 doses: weakness has a latency of 1-2 h). Acetazolamide and thiazides are effective in the treatment. Mutations in SCN4A gene are responsible for this sodium channel disease.
Phosphorylase b kinase deficiency: Muscle-specific phosphorylase b kinase deficiency is an unusual autosomal recessive glycogen storage disorder (chromosome 16q12-13 or 7p12). The majority of patients are male with an age at diagnosis between 15 - 46 years. Clinical features include exercise intolerance, cramps, stiffness, myalgia (with myoglobinuria) and progressive, predominantly distal muscle weakness with atrophy. Serum CK levels may be increased. A forearm ischemic exercise test may show increased lactate production. The demonstration of reduced muscle, erythrocyte or liver phosphorylase b kinase activity by biochemical assay confirms the diagnosis.
Other adult exercise intolerance, cramp and myoglobinuria disorders: phosphoglycerate kinase deficiency (chromosome Xq13), phosphoglycerate mutase deficiency (mainly black Americans, chromosome 7) and lactate dehydrogenase deficiency (chromosome 11).
Proximal myotonic myopathy (PROMM) or myotonic dystrophy type 2: The age of onset is in the 2nd or 4th decade of life (age range 13 – 67 years, median 48 years). This autosomal dominant multisystem disorder is characterized by a characteristic pattern of muscle weakness involving proximal leg weakness (hip flexor and extensors), neck flexors, elbow extensors, thumb and deep finger flexors, and without atrophy (as opposed to distal involvement in DM1), clinical myotonia and myalgias, and cataract (before the age of 40 years). Fluctuating or episodic muscle pain is common in patients > 50 years. Further typical features are cardiac disturbances (asystole, arrhythmias, episodic syncope, conduction block and cardiomyopathy) and hypogonadism (with elevated FSH). Early-onset male frontal balding is found in 20 – 50% of patients. Serum CK (typically less than 5x the upper limits of normal) and g-GT are usually elevated. Diabetes is found in 23% and abnormal glucose tolerance testing shows insensitivity in 75% of patients. Muscle biopsy (vastus lateralis) is abnormal even with normal manual strength testing being normal. The disorder is linked to the DM2 locus at chromosome 3q21. Lack of mental retardation in juvenile cases, less symptomatic distal, facial and bulbar weakness and less pronounced atrophy differentiates this form of dystrophy from DM1. While distal weakness and myotonia are usually the first complaints in DM1, muscle pain, stiffness, fatigue or proximal weakness are the reasons for seeking medical advice in PROMM.
Stiff-person syndrome: The mean age of onset is in the early 40s (30 - 70 years of age). Insidious onset and progressive fluctuating stiffness and rigidity of predominantly axial (abdominal and thoracolumbar paraspinal muscles with difficulty in bending and turning) and, predominantly, proximal lower limb muscles (often asymmetric) and episodic painful spasm superimposed in the rigidity, often precipitated by startle, emotional, and tactile stimuli are the clinical characteristics of this rare disorder. Paroxysms of muscle spasm can be accompanied by profuse diaphoresis, hypertension, tachycardia, and extreme dysphoria. Hyperlordosis, need for cane, shortness of breath and task-specific phobias are commonly observed. EMG shows continuous muscle activity despite relaxation and abolished by iv diazepam. Stimulation (scratching) of the skin increases the motor unit activity. NCVs and distal latencies are normal. Autoantibodies against glutamic acid decarboxylase (anti-GAD65) (ELISA, Boehringer, Mannheim) in serum (>50 ng/ml psitive) and CSF are found in 90% of patients using currently available assays. CSF studies occasionally show increased IgG levels and oligoclonal bands. An association with DRb1 0301 allele has been established in 70% of patients. Three forms of the stiff-person syndrome are generally recognized: 1) autoimmune stiff-person syndrome associated with other autoimmune disorders, and with anti-GAD antibodies. In this form of the disorder, pancreatic islet cell, parietal cell, and thyroid autoantibodies are frequently found; 2) paraneoplastic stiff-person syndrome (associated with breast and small cell lung cancer) with anti-amphiphysin antibodies can be found in serum and CSF. In paraneoplastic stiff-person syndrome, anti-GAD antibodies are usually, but not always, negative; 3) idiopathic stiff-person syndrome with no detectable autoantibodies or autoimmune glandular dysfunction. Frequently, autoimmune disorders are associated with the stiff-person syndrome, including insulin-dependent diabetes mellitus (up to 30% of patients with stiff-person syndrome), thyroiditis, MG, adrenal and ovarian failure, pernicious anemia, and vitiligo. Diazepam is highly effective at reducing spasms and stiffness, but oral doses of up to 300 mg per day may be necessary in some patients. Baclofen has been used with excellent responses both orally and intrathecally with typical dosage ranges of 10-100 mg per day orally, and 50-1000 µg per day intrathecally. Other agents with reported benefit in some patients are tizanidine, methocarbamol, vigabatrin, and valproate (mainly for spasms). Botulinum toxin has been used occasionally for severe muscle spasms with dystonia. Corticosteroids, plasma exchange and iv immunoglobulin infusions may be helpful.
Isaacs syndrome: The disease presents early in life with most patients being < 40 years of age at the time of symptom onset. A dominant mode of inheritance in the familial form of the disease may occur. Progressive painless stiffness, cramping, and weakness are prominent features of the disease. As opposed to fasciculations, patients complain of constant myokymia (writhing movements of the muscles under the skin visualized by continuous "rippling" movements of the muscle). These persist during sleep. Hyporeflexia is also seen in a large percentage of patients. Weakness, when present, tends to be in the distal lower extremities. Autonomic involvement may also be seen with hyperhidrosis and tachycardia. Calf hypertrophy has been described in some patients. "Action" or grip myotonia may be seen. However, percussion myotonia is rare. There may be an associated neuropathy. EMG is the most valuable diagnostic test with continuous motor activity: spontaneous discharges, and rhythmical and continuous firing. The configuration of the wave forms varies, representing either motor units or single fiber discharges. Myokymia is seen electrically. This motor activity persists during sleep. Serum CK levels may be increased. No routine laboratory test is available to detect the antibodies which have been described in research studies. The diagnosis is made by the characteristic history of cramping and stiffness, which persists during sleep and the EMG findings of continuous spontaneous discharges and myokymia in the affected muscle groups. Sleep, narcosis and plexus block have no effect on the continuous motor activity, which can be blocked only succinylcholine. Plasma exchange can result in significant benefit, while the iv immunoglobulin can make symptoms worse. The differential diagnosis includes stiff-person syndrome (prominent muscle stiffness which disappears during sleep with no myokymia on EMG). Anti-GAD antibodies are found in stiff-person syndrome. Benzodiazepines are helpful in stiff-person syndrome, but have no effect in Isaacs syndrome. Phenytoin and carbamazepine are helpful for stiffness in Isaacs syndrome, while there is no effect in stiff-person syndrome. Another disease to be considered in the differential is the Schwartz-Jampel syndrome (myotonia, stiffness syndrome, dwarfism and muscle hypertrophy).
Fatty acid oxidation defects (FAODs): FAODs usually present with a history of hypoglycemia or coma after sustained exercise or prolonged fasting (>24 hours), intermittent bouts of weakness, lethargy, ataxia and coma or episodic vomiting. In addition, disorders of lipid metabolism may cause two main clinical syndromes, namely (1) progressive weakness (long- and very long-chain acyl-CoA dehydrogenase (LCAD, VLCAD), and trifunctional enzyme deficiencies) or (2) normal muscle strength between attacks with episodes of acute, recurrent, reversible muscle dysfunction with exercise intolerance, cramps and acute painful rhabdomyolysis or myoglobinuria (with or without myalgia) induced by fever, fasting or prolonged exercise, valproate therapy, cold exposure (carnitine palmitoyltransferase I and II deficiency (CPT I/II) or (3) both (LCAD, VLCAD, short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCAD), and trifunctional enzyme deficiencies). Identification of the specific enzyme requires tissue (muscle, lymphocytes or cultured fibroblasts) analysis.
LCAD may present as a limb-girdle myopathy.
CPT I/II are the commonest FAOD and the most common cause of recurrent myoglobinuria. CPT is inherited as autosomal recessive trait but occurs most commonly in young adult males. The age of onset in the adult form is typically in the 2nd or 3rd decade of life. Rest does not abort the attacks and there is no second-wind phenomenon. Hypoglycemia with minimal-to-absent ketonemia and ketonuria, mild lactic acidosis, hyperammonemia, and reduced plasma carnitine levels. CK levels are normal or mildly elevated (50%) between attacks. During attacks serum CK levels may rise to 100,000 U/L. In contrast to b-oxidation defects, CPT is characterized by the absence of dicarboxylic aciduria (urine analysis (fasting) for organic acids). Iv glucose improves exercise tolerance while oral glucose is not effective. Assays are available for the measurement of CPT I and II in circulating lymphocytes and cultured fibroblasts. The gene has been mapped to chromosome 1p12. McArdle disease needs to be differentiated from CPT I/II deficiency. Treatment consistes of frequent meals, low in fat and high in carbohydrates before and during exercise and avoid fasting.
Familial nocturnal cramps
Carnitine deficient myopathy: This is autosomal recessive disorder presents with a slowly progressive weakness of limbs and axial muscles starting in childhood or mid-adult life. Cardiomyopathy (often fatal), peripheral neuropathy and hypoketotic hypoglycemia may be concomitant features. Myalgias and cramps are rarely observed. Serum CK levels are normal or mildly increased. In contrast to secondary beta-oxidation defects, there is no dicarboxylic aciduria. Serum and liver carnitine level are normal, but reduced carnitine levels are found in muscle. Muscle biopsy is diagnostic. L-carnitine (50-100 mg/kg/day in divided doses improves muscle strength. Some patients improve on riboflavin and prednisolone.
Becker muscular dystrophy: This form of dystrophy is considered to be a late onset-form of Duchenne muscular dystrophy. It occurs in about 4/100,000 male births. It is a X-linked genetic disorder practically limited to males and transmitted by females. The age of onset is varies between 5 to 45 years. It results in proximal weakness first affecting the pelvic girdle then the pretibial muscles (foot drop), and later on the pectoral muscles and upper limbs. Hypertrophy of the calves, quadriceps femoris and deltoid muscles is a consistent finding. Cardiac involvement occurs and mentation is normal. Serum CK levels are 25 to 200 x increased. EMG shows a myopathic pattern with myotonic discharges. The latter together with muscle biopsy (ELISA dystrophin measurement) should be able to differentiate this disorder from hereditary spinal muscular atrophy. Patients become wheelchair bound before the age of 30 years, but some patients live an advanced age. Female carriers (mothers of the patient) have generally calf hypertrophy, raised serum CK levels and abnormal EMG.
Polyneuropathy: lead- and drug-induced, and uremic and hypothyroidism-induced polyneuropathy.
GM2 gangliosidosis (hexosaminidase deficiency): Late-onset forms of GM2 gangliosidosis: Tay-Sachs disease (hexosaminidase A deficiency) and Sandhoff (hexosaminidase A and B deficiency) disease exist. Late-onset forms (age of > 60 years) of GM2 gangliosidosis occur particularly in Ashkenazi Jew descendants, but have been identified in other populations as well. Early and dominant sensory disturbances (axonal sensory polyneuropathy) such as mechanoallodynia are often the first symptoms. In addition, almost half of the patients present with psychiatric manifestations (psychosis), slowly progressive SMA with muscle weakness (often limb-girdle in distribution) and nocturnal cramps and other combinations of MND (fasciculations, spasticity and amyotrophy), progressive spinocerebellar ataxia and ophthalmoplegia. Other manifestations such as dementia, dystonia, and seizures are less common. In contrast to chronic (or adult) GM1 gangliosidosis, extrapyramidal features (dystonia, parkinsonism) are not a prominent feature and are explained by the fact that in chronic (or adult) GM2 gangliosidosis storage neurons are more widely distributed (thalamus, substantia nigra and other brainstem nuclei, and cerebellum). MRI may reveal severe cerebellar atrophy. The diagnosis is based on serum and leukocyte total hexosaminidase (Sandhoff disease) and hexosaminidase A (Tay-Sachs disease), which decreased in both conditions (2 to 4% of normal). Further confirmation can be received from rectal biopsy (ganglion cells). GM2 gangliosidosis is autosomal recessive and the HEXA gene is located on chromosome 15q23-24. All patients with recessive atypical ataxia or unusual motor neuron disorder should be screened for lysosomal storage disease, particularly if the parents are consanguineous. The disease may mimick progressive muscular dystrophy.
Adult-onset amyotrophic lateral sclerosis (ALS): The prevalence of ALS ranges from 4-6/100,000. Sporadic ALS accounts for 90% of cases, whereas autosomal form accounts for the remaining 5-10%. The onset can occur at any age in adult life, but most patients are more over 50 years of age. Typically, the disease begins distal, asymmetric and focal, and then spreads in an anatomic pattern. Initial features are either those of dysfunction of the lower motor neuron (fatigue, weakness of distal limb muscles e.g. drop foot, muscle atrophy e.g. wasted small hand muscles (difficulty with buttons and key manipulation), fasciculations, stiffness in the fingers and cramps in the brachioscapular myotoma) or upper motor neuron (slowed movements, hyperreflexia, hypertonia and spasticity). The legs remain relatively preserved. Later on, bulbar involvement ensues causing dysphagia, drooling of saliva, dysphonia, tongue atrophy with fasciculations, spastic dysarthria ('hot potato speech') or aspiration. Signs of pseudobulbar palsy (bilateral corticobulbar involvement) usually evolve during the course of the disease and may become evident such as brisk jaw jerk, uncontrolled emotional incontinence with sparing of cognitive function. Autonomic functions and eye movements remain always preserved. An initially tentative diagnosis may become more secure as the disease progresses. Hence a triad of atrophic weakness of the hands and forearms, slight spasticity in the upper and lower limbs, and generalized hyperreflexia in the absence of sensory symptoms usually leaves little doubt. Upper MN and lower MN findings (clinically or on EMG) in at least three of four anatomical regions (bulbar, cervical, thoracic and lumbosacral) are required for definite clinical diagnosis. Forced vital capacity is used for follow-up of respiratory muscle strength. SNAPs should be normal. The NCVs are normal but the amplitude may be slightly reduced. CSF protein is normal or slightly elevated. Intriguingly, SEPs are abnormal. Brain MRI may show slight atrophy of the motor cortices and degeneration of the motor tracts (subtle symmetric increased T2 signal intensity in the posterior limb of the internal capsule, brainstem, and spinal cord). Variants in the pattern of evolution exist (progressive bulbar palsy; early thoracic, abdominal, or posterior neck muscle involvement; hemiplegic forms; proximal limb or shoulder girdle amyotrophy etc.). 20% of familial forms and 5% of the sporadic forms have mutations in the gene for cytosolic, copper/zinc superoxide dismutase (SOD1) encoded on chromosome 21q22.1 and are transmitted as an autosomal dominant trait. Invariably, death from respiratory failure usually occurs within 3-5 years from onset of symptoms in 50% of patients. 5-year survival after diagnosis is about 7%. Familial ALS may present as an LMN syndrome. Riluzole (50mg bid), a glutamate antagonist, prolongs tracheostomy free survival by 3–6 months. Approximately 10% of patients stop the drug because of adverse events, principally gastrointestinal intolerance and asthenia. CBC and liver function tests should be monitored every month. Riluzole does not produce an improvement in symptoms. Physiotherapy remains the mainstay of treatment. Weight loss should be tackled by early institution of percutaneous endoscopic gastrostomy feeding or gastrostomy. Sialorrhea is generally managed with anticholinergic agents including atropine or amitriptyline taken orally, hyoscine (scopolamine) transdermally, glycopyrronium bromide subcutaneously, or via gastrostomy. The following disorders in order of appearance are most commonly misdiagnosed as ALS: multifocal motor neuropathy with conduction blocks (anti-GM1 antibodies), CIDP, MG, MS, sensorimotor neuropathy, syringomyelia, cervical spondylitic radiculomyelopathy (neuroimaging, pain in neck and shoulders, sensory changes), and IBM. In relation to progressive bulbar palsy, MG, polymyositis, muscular dystrophy and Kennedy disease (X-linked) needs to be considered. MND has been observed in association with certain systemic conditions such as monoclonal gammopathy, lymphoma, thyroid disorders, hyperparathyroidism, HTLV-1 or HIV infections, heavy metal toxicity or high titers of anti-GM1 ganglioside antibodies.
Central core myopathy (CCM): Although mostly occurring in childhood, late onset forms exist. This autosomal dominant disorder presents often with mild and proximal weakness and muscle cramps following exercise. There are no fasciculations or myotonia. Pes cavus, pes planus and kyphoscoliosis may occur at young age. Serum CK levels may be normal or slightly increased. EMG shows small amplitude motor unit potentials with a normal interference pattern. The findings on muscle biopsy are pathognomonic. Malignant hyperthermia is the most common complication. The gene is located at chromosome 19q13.1. The disease is often mistaken for LGMD.
Limb-girdle muscular dystrophy (LGMD): The LGMD diagnostic criteria are the following: face-sparing, slowly progressive predominant proximal symmetric weakness with primarily lower limb onset, normal to mildly raised serum CK activity, myopathic EMG and dystrophic changes on muscle biopsy. Cardiac involvement is infrequent. The age of onset varies from late childhood to early adulthood. Fourteen genetically distinct forms of LGMD have been identified the majority of LGMD are autosomal recessive (LGMD2) the others autosomal dominant (LGMD1). Major differential diagnosis of LGMD is X-linked recessive dystrophinopathies, FSHMD and EDMD.
The most important autosomal recessive forms presenting in adulthood are:
1) calpainopathy (CAPN3 gene chromosome 15q15)(LGMD 2A) Described in the Amish population, Réunion and Brazil. Age of onset usually between 8 - 15 years (range 2-40 years). The disorder is clinically characterized by early contractures of Achilles tendon (tendency to toe walk), proximal shoulder weakness with scapular winging, adductor weakness, difficulties in running and walking, and atrophic calves. Serum CK levels are very high (>10x increased). Patients are wheelchair bound after 10-28 years (mean age of 30). The diagnosis is based on Western blotting or molecular testing (immunostaining of muscle biopsy is unreliable).
2) dysferlinopathy (LGMD 2B) arises from the same gene (chromosome 2p13) as Miyoshi myopathy. The disease has been identified in Palestinian and Sicilian families. Clinically it can present as proximal or distal muscle leg weakness with difficulties in running and walking, inability to toe walk. Age of onset varies between 17-23 years. Serum CK levels are extremely high. The diagnosis is based on Western immunoblotting on muscle biopsy for dysferlin protein. Important differential diagnosis is polymyositis. Therefore any patient with polymyositis not responding to steroids should be considered as probable dysferlinopathy.
3) telethoninopathy (LGMD 2G gene chromosome 17q11) is clinically characterized by foot drop with difficulty in running and walking. It affects proximal muscles of both upper and lower limbs. The age of onset is in the early teens. Serum CK levels are substantially increased. Patients are wheelchair bound after 18 years. The diagnosis is based on immunohistochemistry of muscle biopsy.
Adult autosomal dominant forms are:
1) LGMD 1A (myotilin gene chromosome 5q22.3-31.3), clinically characterized by proximal weakness of hip and shoulder girdles, dysarthric speech, tightened heel cords. The age of onset is around 27 years. Serum CK values are markedly elevated. DNA testing is the only diagnostic modality.
2) LGMD 1B (chromosome 1q11)(similar to Bethlem myopathy (chromosome 21q)) Early manifestations are non-disabling contractures of elbows, ankles, interphalangeal joints of the fingers later followed by proximal symmetric weakness in the lower limbs. Very important here are the cardiac irregularities (e.g. arrhythmias, conduction block, etc.). Serum CK values are normal or slightly elevated. This form can be differentiated from EDMD by absence of contractures in neck and spine. Unlike in LGMD 1B, patients with Bethlem myopathy do not have cardiac involvement.
3) LGMD 1D (chromosome 6q23) patients suffer significant cardiac involvement and proximal symmetric weakness in the lower limbs. The age of onset is before 25 years. Serum CK values are slightly elevated (2-4x). There is no diagnostic test available.
Infectious diseases: Lyme disease and meningoencephalitis (West-Nile virus and anthrax).