Flashcards in muscle diseases: Deck (32)
What gene mutation causes central core myopathy?
Central core disease is caused by mutations of the ryanodine receptor (RYR1, on chromosome 19).
What gene mutations cause multiminicore myopathy?
Multiminicore disease may be caused by recessive mutations in selenoprotein N1 (SEPN1), and skeletal muscle ryanodine receptor (RYR1).Selenoprotein contains cysteine were sulfur (16) is replaced by selenium (34), which occurs in glutathione and other enzymes.
What genetic mutations cause centronuclear myopathy?
Centronuclear myopathies may be due to mutations of dynamin 2 (DNM2, chromosome 19), or myelotubularin protein (MTM1, X-chromosome, PI3 phosphatase).
Dynamin is a GTPase associated with pinching vesicles for release from cell membranes.
What genetic mutations cause congenital fiber type disproportion myopathy?
Congenital Fiber Type Disproportion is genetically heterogeneous and maybe due to mutations in alpha-actin (ACTA1, chromosome 1), slow skeletal alpha-tropomyosin 3 (TPM3, chromosome 1), selenoprotein N1 (SEPN1), or skeletal muscle ryanodine receptor (RYR1).
What additional mutations are known to cause nonspecific congenital myopathy?
There are rare additional myopathies due to mutations in MEGF10 (multiple epidermal growth factor like domains 10), EMARDD (myopathy, areflexia, respiratory distress, and dysphagia, early onset), and SMARD1 (spinal muscular atrophy, distal, autosomal recessive, 1).MEGF10 regulates muscle satellite cell generation.
What is nebulin?
Nebulin is an actin binding protein (600 – 900 kDa) that may act as a ruler for actin length. It also inhibits ATPase activity in a calcium-calmodulin sensitive manner. It's mutated form results in nemaline myopathy.
What types of myopathy develop from mutations in ACTA1 gene (actin α-isoform).
Mutations alter the structure of muscle with 3 types of myopathy, type 3 nemaline myopathy, congenital myopathy with excess of thin micro filaments, and fiber type disproportion.ACTA1 is predominant in skeletal muscle.
What is SMARD1 (spinal muscular atrophy, distal, autosomal recessive, 1 due to?
Spinal muscular atrophy with respiratory distress type I (SMARD 1) is due to motor neuron atrophy from a recessive mutation in the IGHMBP2 (Immunoglobulin helicace mu-binding protein 2) gene.
What are the consensus criteria for diagnosis of Sjogren's syndrome?
The American European consensus group definition for Sjogren's syndrome includes:1. Ocular symptoms of inadequate tear production2. Ocular signs of formula damage due to inadequate tearing.3. Oral symptoms of decreased saliva production4. Salivary gland histopathology demonstrating foci of lymphocytes.5. Tests indicating impaired salivary gland function.6. SSA/anti-Ro, SSB/anti-La autoantibodies.
The sensation of eye dryness correlates best with what corneal abnormality?
Dryness correlates best with increased friction of the upper lid moving over the cornea.
What skin changes can occur in Sjogren's syndrome?
Skin involvement in Sjogren's syndrome can include xerosis, cutaneous vasculitis, Raynaud's phenomenon, and annular erythema,
What do elevated platelet factor 4 plasma levels mean in systemic sclerosis?
Elevated plasma levels of platelet factor 4 (CXCL-4) correlate with pulmonary fibrosis and pulmonary hypertension in systemic sclerosis.
What are the common causes of angioedema?
Drug reaction to Ace inhibitors are the most common cause, but NSAID's, calcium channel blockers, estrogens, fibrinolytic agents, any new medication or significant increase in dosage should also be suspect. Complement factor 1 inhibitor (C1-INH) deficiency either inherited (Types 1, 2 or 3) or acquired are not as common. Inherited forms are due to absent protein, defective protein, or inherited problems with clotting factors causing bradykinin release. Aquired C1-INH deficiency can occur with malignancies where autoantibodies develop to C1-INH.
Name additional causes for thromboembolism aside from antiphospholipid antibody syndrome.
Arterial thrombosis/embolism from-blood problems: Inherited coagulation or anticoagulant factor disorders, (TTP/HUS), Hellp syndrome, sepsis with multiorgan failure, nephrotic syndrome, disseminated intravascular coagulation, hyper viscosity, sickle cell disease, atrial fibrillation, platelet dysfunction, endocarditis, decompression sickness, dysfibrinogenemia, homocystinemia, myeloproliferative disorders. Vessel problems: atherosclerosis, cholesterol emboli, paradoxical embolism, polyarteritis nodosa, ANCA positive vasculitis.Medications -heparin, phenothiazines, hydralazine, procainamide, phenytoin.
What treatment for arthritis can be started prior to determining a definite diagnosis?
Acetaminophen, OTC NSAIDs. If infection is unlikely then prednisone 5 mg bid, intraarticular injection with Depo Medrol if joint fluid WBC is<10,000. Prolonged daily high dose prednisone, sulfasalazine, hydroxychloroquine (Plaquenil), methotrexate, or leflunomide (Arava) would require a definite diagnosis.
What are the characteristics of inflammatory backache?
Inflammatory backache is defined as age of onset prior to age 40, incidious onset, improvement with exercise, no improvement with rest, pain at night which improves on arising. Other features suggestive of spondylitis include: arthritis diagnosed by a physician, heel enthesitis, acute uveitis, dactylitis, psoriasis diagnosed by a physician, inflammatory bowel disease, good response to NSAIDs, reactive arthritis, inflammatory bowel disease, elevated C-reactive protein, first or second-degree relative with a ankylosing spondylitis.
What is the major complication when complete rest is used to treat tendinitis?
Without movement, tendons become weak and stiff such that whatever inflammatory reaction resolves due to rest, quickly returns when activity is resumed.
What are the red flags indicating the need for further evaluation in cases of backache of recent onset?
Red flags indicating possible definite cause for backache include: trauma, unexplained weight loss, age over 50 especially if osteoporotic, unexplained fever, history of urinary tract or other infections, immunosuppression, diabetes mellitus, history of cancer, intravenous drug abuse, long use of corticosteroids, age greater than 70, focal neurologic deficit, progressive or disabling symptoms, associated bowel or bladder dysfunction, duration longer than six weeks, and prior spinal surgery.
What are the diagnostic criteria for Behcet's disease?
Behcet's disease is characterized by the presence of recurrent aphthous ulcers with at least 3 episodes in any 12 month period. There must be at least 2 additional features such as: recurrent genital ulceration, eye lesions, skin lesions, or positive pathergy test. Anterior or posterior uveitis on slit lamp examination or retinal vasculitis documented by an ophthalmologist, erythema nodosum or papulopustular skin lesions or pseudo-folliculitis with characteristic achneiform nodules observed by a physician. Other features commonly explained by Behcet's disease include arterial aneurysms in the heart, kidney, or pulmonary vasculature, oligo or polyarticular non deforming arthritis, renal amyloidosis or glomerulonephritis, pericarditis or myocarditis. A positive pathergy test is defined by a papule 2 mm or more mm in size developing within 48 hours after the insertion of a 20gauge needle 5 mm into the forearm skin. Aseptic meningoencephalitis, cerebral vasculitis, recurrent phlebitis, arteritis, synovitis, or focal bowel ulceration might substitute for pathergy in European or North American populations.
What life-threatening complications occur in Behcet's disease?
The greatest morbidity and mortality comes from neurologic, ocular, and large vessel arterial or venous disease.
What treatment is used to manage glomerulonephritis seen in Behcet's syndrome?
Renal disease seems to behave like granulomatosis with polyangiitis, so that rituximab might be effective if glomerulonephritis is present. Those patients with amyloidosis do better with colchicine.
What are the diagnostic criteria for chronic fatigue syndrome?
Chronic fatigue syndrome criteria include documented fatigue for six months or more, and at least four of the eight following symptoms: post exertion malaise, impaired memory/concentration, unrefreshing sleep, muscle pain, multi-joint pain without redness or swelling, tender cervical or axillary lymph nodes, sore throat, and headache. Fatigue must be severe enough to interfere with work or usual activities.
Why are sensitive features of an illness which are non specific important to recognize?
Highly sensitive features or an illness when absent, weigh against the likelihood of that illness.
With systemic diseases can cause muscle enzyme elevation?
Systemic disorders such as inflammatory myopathy (polymyositis/dermatomyositis, systemic lupus erythematosus, and mixed connective tissue disease with antibodies to RNP), infectious myopathy, drug induced myopathies (alcohol, lipid lowering drugs, cocaine, antimalarial drugs, antipsychotic drugs, colchicine, antiretroviral drugs, ipecac, Interferon alpha and penicillamine), dystrophic myopathies, neuroleptic malignant syndrome, metabolic myopathies, hyperthermia, motor neuron disease, endocrine myopathy, and periodic paralysis should be considered. Presymptomatic myopathies as in the early stages of polymyositis, distal myopathy, mitochondrial myopathies, inclusion body myopathy, muscular dystrophy, myotonic dystrophy, and predisposition to malignant hyperthermia.
What are the diagnostic criteria for fibromyalgia?
The criteria for fibromyalgia include a widespread pain index >7, symptom severity >5. If widespread pain index is only 3 – 6 then symptom severity needs to be >9.Symptoms present >3 months.No other condition is present to explain the pain.Widespread pain index is derived from counting the areas of tenderness including the neck, jaw, shoulder, upper and lower arm, chest, abdomen, upper and lower back, hips, upper or lower legs for a maximum of 19 areas.Symptom severity score is derived from weighting fatigue, waking up refreshed, cognitive symptoms on a 0 – 3 scale. Somatic symptoms are rated from 0 – 3 in terms of their number. The final score is between 0 – 12. Best predictor in normals who develop chronic widespread pain is non restorative sleep.
What is diagnostic of inclusion body myositis?
Biopsy shows basophilic rimmed vesicles on frozen section and permanent sections show variation fiber size. On electron microscopy the inclusions resemble myxovirus particles. CD8 + T cells predominate in the inflammatory infiltrate. Inclusion body myositis generally occurs in older men causing slowly progressive mostly distal muscle weakness and lower than expected increases in muscle enzymes. EMG tends to have more fibrillation and polyphasic potentials and MRI changes involve distal anterior muscle groups. Rare genetic enzymatic abnormalities
What genetic defects occur in Nemaline myopathy?
Nemaline myopathy results from congenital abnormalities in the thin filaments due to abnormalities in nebulin (NEB, chromosome 2), alpha-actin (ACTA1, chromosome 1), slow skeletal alpha-tropomyosin 3 (TPM3, chromosome 1), beta tropomyosin 2 (TPM2, Chromosome 9), cofilin 2 (CFL2, Chromosome 14).
What is the natural course of enthesitis?
Enthesitis refers to the condition where in the site of muscle/tendon and bone attachment becomes painful related to repetitive excessive tension. The term implies inflammation however pathologically there is minimal change so that the precise pain generator is undefined. Probably prostaglandins, cytokines, from either the periosteum or muscle participate in the process. Most instances probably spontaneously resolve however a vicious cycle of damage followed by insufficient healing can lead to persistent pain lasting maybe priorhs, or years in duration. Enthesitis associated with spondyloarthropathy may require anti-TNF agents to stop the progression.
What is the usual initial treatment for polymyositis, and dermatomyositis?
Initial treatment of polymyositis, dermatomyositis, and inclusion body myositis are similar. A course of prednisone at 1 mg per kilogram (Max 80 mg) daily for six weeks followed by reduction (10 mg per week until 40 mg daily, then 5 milligrams per week until 20 mg daily, 2.5 mg per week until 10 mg daily, then 1 mg every two weeks until 5 mg daily). Responders may be off treatment by one year. Azathioprine at 2.5 mg per kilogram or methotrexate at 25 mg per week is usually used along with low-dose prednisone (5 to 15 mg daily).