Limb-girdle muscular dystrophy - AbsoluteAstronomy.com

Limb-girdle muscular dystrophy or Erb's muscular dystrophy is an autosomal class of muscular dystrophy

Muscular dystrophy

Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

that is similar but distinct from Duchenne muscular dystrophy

Duchenne muscular dystrophy

Duchenne muscular dystrophy is a recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty walking, breathing, and death. The incidence is 1 in 3,000 boys. Females and males are affected, though females are rarely affected and are more often carriers...

and Becker's muscular dystrophy

Becker's muscular dystrophy

Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis....

. Limb-girdle muscular dystrophy encompasses a large number of rare disorders.

Presentation

The term "limb-girdle" is used to describe these disorders because the muscles most severely affected are generally those of the hips and shoulders -- the limb girdle muscles.

Common symptoms of limb-girdle muscular dystrophy are muscle

Muscle

Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

weakness, myoglobinuria

Myoglobinuria

Myoglobinuria is the presence of myoglobin in the urine, usually associated with rhabdomyolysis or muscle destruction. Myoglobin is present in muscle cells as a reserve of oxygen.-Causes:...

, pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

, myotonia

Myotonia

Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation. Generally, repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed...

, cardiomyopathy

Cardiomyopathy

Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...

, elevated serum

Blood plasma

Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

Creatine kinase

Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...

, and rippling muscles.

The muscle weakness is generally symmetric, proximal, and slowly progressive.

In most cases, pain is not present with LGMD, and mental function is not affected.

LGMD can begin in childhood, adolescence, young adulthood or even later. The age of onset is usually between 10 and 30. Both genders are affected equally. When limb-girdle muscular dystrophy begins in childhood the progression appears to be faster and the disease more disabling. When the disorder begins in adolescence or adulthood the disease is generally not as severe and progresses more slowly.

There is no sensory neuropathy or autonomic or visceral disfunction at presentation.the specific dermatomes affected can be demonstrated clinically,and although lower limb deep tendon reflexes and plantar reflex are lost, abdominal reflexes are preserved

Prognosis

The distal muscles are affected late in LGMD, if at all. Over time (usually many years), the person with LGMD loses muscle bulk and strength. Eventually, s/he may need a power wheelchair or scooter, especially for long distances. The various forms of LGMD are highly variable, and can be variable even among persons with the same form of LGMD. In its most severe form, LGMD2C, the symptoms are usually similar to Duchenne Muscular Dystrophy, with individuals losing the ability to walk between ages 10 and 12.

While LGMD isn't typically a fatal disease, it may eventually weaken the heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

and respiratory muscles, leading to illness or death due to secondary disorders. In its most severe form, LGMD2C, lifespans are typically limited to the 20s or early 30s.

Diagnosis

A person need to perform "Muscle biopsy" test in order to know whether he has muscular dystrophy or not , "Genetic testing" need to be done in order to find the type of LGMD

Currently a "CHIP" is being developed by an organization called "NMD CHIP"

The project is designing chips for the diagnosis of mutations already known to cause Duchenne / Becker muscular dystrophies (DMD/BMD), limb girdle muscular dystrophies (LGMD), congenital muscular dystrophies (CMD), and hereditary motor-sensory neuropathies or Charcot-Marie-Tooth neuropathies (CMT). These diagnostic chips are described as "known-gene chips".

A project website has been set up at www.nmd-chip.eu which enables dissemination of information about the project to stakeholders.

Genetics

LGMD is typically an inherited disorder, though it may be inherited as a dominant, recessive, or X-linked genetic defect. The result of the defect is that the muscles cannot properly form the protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s needed for normal muscle function. Several different proteins can be affected, and the specific protein that is absent or defective identifies the specific type of muscular dystrophy. Among the proteins affected are α, β, γ and δ sarcoglycan

Sarcoglycan

The sarcoglycans are a family of transmembrane proteins involved in the protein complex responsible for connecting the muscle fibre cytoskeleton to the extracellular matrix, preventing damage to the muscle fibre sarcolemma through shearing forces.The dystrophin glycoprotein complex is a...

s. The sarcoglycanopathies

Sarcoglycanopathies

The sarcoglycanopathies are a collection of diseases resulting from mutations in any of the four sarcoglycan genes, α, β, γ or δ.The four sarcoglycanopathies are : α-sarcoglycanopathy, LGMD2D; β-sarcoglycanopathy, LGMD2E; γ-sarcoglycanopathy, LGMD2C; δ-sarcoglycanopathy, LGMD2F...

could be possibly amenable to gene therapy

Gene therapy

Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...

Treatment

Treatment for LGMD is primarily supportive. Exercise and physical therapy

Physical therapy

Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...

are advised to maintain as much muscle strength and joint flexibility as possible. Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is also required. IVIg may increase strength in some forms and prevent progression in others, possibly through the prevention of fibrosis and inflammation without the secondary weakening caused by corticosteroids.

Research

There is currently not an effective treatment or cure to address the underlying genetic defects that cause LGMD. There is a variety of research underway targeted at various forms of LGMD. Methods thought to hold significant promise for an effective treatment include "exon skipping" and gene therapy. Several clinical trials are underway and seeking to apply these methodologies to various limb girdly dystrophies.

List of limb-girdle muscular dystrophies

The "LGMD1" family is autosomal dominant, and the "LGMD2" family is autosomal recessive.

Name	OMIM	Location >- \| LGMD1A		>- \| LGMD1B		LMNA LMNA Lamin A/C also known as LMNA is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.-Function:... >- \| LGMD1C		CAV3 Caveolin 3 Caveolin-3 is a protein that in humans is encoded by the CAV3 gene.-Interactions:Caveolin 3 has been shown to interact with Epidermal growth factor receptor, Dysferlin and Dystroglycan.-Further reading:... >- \| LGMD1D		>- \| LGMD1E		>- \| LGMD1F		>- \| LGMD1G		>- \| LGMD2A		CAPN3 CAPN3 Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.-External links:* The MEROPS online database for peptidases and their inhibitors: ** LOVD mutation database:... >- \| LGMD2B		>- \| LGMD2C		SGCG SGCG Gamma-sarcoglycan is a protein that in humans is encoded by the SGCG gene.-Interactions:SGCG has been shown to interact with FLNC.-External links:* LOVD mutation database:... >- \| LGMD2D		SGCA SGCA Alpha-sarcoglycan is a protein that in humans is encoded by the SGCA gene.-External links:* LOVD mutation database:... >- \| LGMD2E		SGCB SGCB Beta-sarcoglycan is a protein that in humans is encoded by the SGCB gene.-External links:* LOVD mutation database:... >- \| LGMD2F		SGCD SGCD Delta-sarcoglycan is a protein that in humans is encoded by the SGCD gene.-Interactions:SGCD has been shown to interact with FLNC.-External links:* LOVD mutation database:... >- \| LGMD2G		TCAP TCAP (gene) Telethonin is a protein that in humans is encoded by the TCAP gene.-Interactions:Telethonin has been shown to interact with Titin, MYOZ1 and ANKRD2.- External links :*... >- \| LGMD2H		TRIM32 TRIM32 Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.- Structure :... >- \| LGMD2I		>- \| LGMD2J		TTN Titin Titin , also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured... >- \| LGMD2K		POMT1 POMT1 Protein O-mannosyl-transferase 1 is an enzyme that in humans is encoded by the POMT1 gene. It is a member of the dolichyl-phosphate-mannose-protein mannosyltransferases.- Function :... >- \| LGMD2L		>- \| LGMD2M		>- \| LGMD2N		POMT2 POMT2 Protein O-mannosyl-transferase 2 is an enzyme that in humans is encoded by the POMT2 gene.- Function :POMT2 encodes an integral membrane protein of the endoplasmic reticulum that shares significant sequence similarity with a family of protein O-mannosyltransferases of S. cerevisiae... >- \| LGMD2O		POMGNT1 POMGNT1 Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 is an enzyme that in humans is encoded by the POMGNT1 gene.- Function :...

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