THE DISORDER OF MUSCLES / MYOPATHIC DISEASE:

Introduction :

Disorders of the Muscle (Myopathic Disease) Primary muscle disease

can decrease the ability of anormal neural impulse to generate effective
muscle contraction. Some commonly recognized myopathies include
Duchenne muscular dystrophy (DMD), myotonic dystrophy, and polymyositis.

Disorders of the Muscle (Myopathic Disease)

Primary muscle disease can decrease the ability of a normal neural impulse
to generate effective muscle contraction. Some commonly recognized
myopathies include Duchenne muscular dystrophy (DMD), myotonic
dystrophy, and polymyositis. Duchenne muscular dystrophy is a genetic
muscle-wasting disorder caused by mutations in the dystrophin gene.17
Because it is an X-linked recessive disorder with shortened survival, it affects
essentially only males. The diagnosis is made when a dystrophin mutation is
found in DNA from circulating white blood cells or when dystrophin is found
to be absent or abnormal in biopsied muscle tissue.

Another term: Pseudohypertrophic muscular dystrophy

Sign and Symptoms:

Symptoms of Duchenne muscular dystrophy (DMD) most often appear

between the ages of 2 and 4 years, though they can begin as early as
infancy or be noticed later in childhood.
DMD causes muscle weakness that worsens over time, so common
symptoms include:

1. Progressive muscle weakness and atrophy (loss of muscle bulk) that

begins in your
child’s legs and pelvis. It occurs less severely in their arms, neck and other
areas of their
body.
2. Calf muscle hypertrophy (increase in muscle size).
3. Difficulty climbing up stairs.
4. Difficulty walking that gets worse over time.
5. Frequent falls.
6. Waddling gait (walk)
7. Toe walking.
8. Fatigue.
Other common symptoms of DMD include:

1. Cardiomyopathy.
2. Breathing difficulties and shortness of breath.
3. Cognitive impairment and learning differences.
4. Delayed speech and language development.
5. Developmental delay.
6. Scoliosis (spine curvature).
7. Short stature (height)

A classic sign of Duchenne muscular dystrophy is trouble getting up from a

lying or sitting position, as manifested by a positive Gowers's sign.

Duchenne muscular dystrophy mainly affects boys, but girls who are carriers
for DMD can sometimes have milder symptoms.

Symptoms of muscle weakness usually appear by the age of 2 years to 4

years, but sometimes, are noted as late as 6 years.

Risk factors:

Family History: A family history of DMD increases the risk of having or

being acarrier of the disease.

Carrier Mother: If a mother is a carrier of the mutated gene, there is a

50%chance that her male children will inherit the disease.

What causes DUCHENNE MUSCULAR DYSTROPHY

Duchenne muscular dystrophy (DMD) is caused by a change (mutation) inthe

gene that gives instructions for a protein called dystrophin. Dystrophin is a
critical part of the dystrophin-glycoprotein complex (DGC), which plays an
important role as a structural unit of muscle. In DMD, both dystrophin and
DGC proteins are missing, which ultimately leads to the death (necrosis) of
muscle cells. People with DMD have less than 5% of the normal quantity of
dystrophin needed for healthy muscles.
Duchenne muscular dystrophy has X-linked recessive inheritance, but
about30% of cases happen spontaneously without a family history of the
condition.
X-linked means the gene responsible for DMD is located on the X
chromosome, one of two sex chromosomes. Males have an X and Y
chromosome, and females have two X chromosomes.

Diagnostic and test:

If your child's provider suspects that your child may have DMD, they’ll
likelyorder the following tests:

Creatine kinase blood test: Your muscles release creatine kinase when
they’re damaged, so elevated levels may indicate DMD. Levels typically peak
by age 2 and can be more than 10 to 20 times above the normal range.

Genetic blood test: A genetic blood test that looks for a complete or
nearcomplete absence of the dystrophin gene can confirm the diagnosis of
DMD.

Muscle biopsy: Your child’s provider may take a small sample of their
muscle tissue from a muscle in their thigh or calf. A specialist will then lookat
the sample under a microscope to look for signs of DMD.

Electrocardiogram (EKG): As DMD almost always affects your heart, your

child’s provider will likely perform an EKG to look for characteristic signs of
DMD and to check the health of your child’s heart.

Management and treatment:

Supportive therapies for DMD include:

Corticosteroids: Corticosteroids, such as prednisolone and deflazacort, are

beneficial for delaying muscle strength loss, improving lung
function,delaying scoliosis, slowing the progression of cardiomyopathy (heart
weakness) and prolonging survival. Medication to treat cardiomyopathy:
Early treatment with ACE inhibitorsand/or beta-blockers may slow the
progression of cardiomyopathy and prevent the onset of heart failure.
Physical therapy: The main goal of physical therapy for DMD is to prevent
contractures (permanent tightening of your muscles, tendons and skin).
Thisusually involves certain stretching exercises.

Surgery to help treat scoliosis and contractures: Surgery to release

contractures may be necessary for severe cases. Surgery to correct scoliosis
may improve lung and breathing function.

Exercise: Your child’s healthcare provider will likely recommend

gentleexercise to avoid muscle atrophy due to a lack of use. This is usually a
combination of swimming pool and recreation-based exercises.

Other supportive therapies for DMD include:

Mobility aids, such as braces, canes and wheelchairs.

Tracheostomy and assisted ventilation for respiratory failure.

MYOTONIC DYSTROPHY:

Myotonic dystrophy is the most common form of muscular dystrophy in

adults, with an estimated frequency of I in 8000 persons."1 Myotonia, or
delayed muscle relaxation, is the key feature of this neuromuscular disorder.
This autosomal dominant disorder causes progressive muscle weakness,
abnormalities of the cardiac conduction system, endocrine
dysfunction, and cataracts.Respiratory dysfunction in myotonic dystrophy is
common, usually occurring late in the course of disease, and can indude
respiratory muscle weakness, OSA, and bulbar muscle dysfunc-tion leading
to aspiration. Sleep-disordered
breathing is common, even at an early age.

Patients with myotonic dystrophy can be very sensitive to anesthesia and

respiratory depressants. Both respiratory failure and prolonged
neuromuscular blockade have been reported in patients with myotonic
dystrophy given usual doses of these agents. NIV can be used
postoperatively, especially if the patient has had the opportunity to adjust to
NIV
preoperatively. Pro-longed monitoring after surgery is prudent.

There are two main types:

Myotonic Dystrophy Type 1
(DM1) and Myotonic
Dystrophy Type 2 (DM2).
Dystrophia myotonica: A Latin term used to describe the condition.
Steinert's disease: Named after the German doctor who first identified the
disorder.

Myotonic muscular dystrophy: Another name for thecondition.

ETIOLOGY & EPIDEMIOLOGY/PATHOPHYSIOLOGY

Etiology (Cause): Myotonic dystrophy is caused by genetic mutations in

the DMPK (DM1)
or CNBP (DM2) genes.

Epidemiology :
Myotonic dystrophy is inherited in an autosomal dominant manner, meaning
that if one parent has the condition, there is a 50% chance their child will
inherit it. The condition can manifest at any time from infancy to adulthood

Pathophysiology:
Mutations in the DMPK gene lead to the production of a toxic RNA, which
interferes with the normal function of other genes. Mutations in the CNBP
gene disrupt the function of the protein it produces, leading to similar
problems. These genetic changes result in muscle weakness, myotonia, and
other systemic complications.

Risk factors:

Family History: The primary risk factor is having a family history of

myotonic dystrophy.

Congenital Myotonic Dystrophy: A more severe form of the disease can

occur in babies of mothers who have DM1.

Sign and Symptoms:

Myotonia:
Difficulty relaxing muscles after use, often manifested as difficulty releasing
a grip.
Muscle Weakness:
Progressive weakness, typically starting in the hands, feet, neck, and face,
and then
spreading to other muscles.
Other Symptoms:
Early onset cataracts.
Cardiac conduction defects (abnormal heart rhythms).
Learning difficulties.
Daytime sleepiness.
Infertility.
Endocrine disturbances.
Gastrointestinal problems.

Diagnostic And Tools:

Genetic Testing: Blood tests are used to identify mutations in the DMPK or
CNBP genes.

Electromyography (EMG): Measures the electrical activity of muscles,

which can help diagnose myotonia.

Muscle Biopsy: A small sample of muscle tissue is examined under a

microscope.
Electrocardiogram (ECG): Measures the electrical activity of the heart to
assess for cardiac abnormalities.

TREATMENT AND MANAGEMENT:

There is currently no cure for myotonic dystrophy, and treatment focuses on

managing the symptoms and complications.

Interdisciplinary Approach: Treatment involves a team of specialists,

including neurologists, cardiologists, ophthalmologists, and physical
therapists.

Medications: There are no medications that target the underlying genetic

cause of myotonic dystrophy.

Medications may be used to manage specific symptoms, such as heart

problems or muscle spasms.

Physical Therapy: Helps to maintain muscle strength and function.

Occupational Therapy: Helps patients adapt to daily living activities.

POLYMYOLITIS:

Polymyositis is a rare autoimmune disease that makes your immune system

attack your muscles. It’s a type of myositis. Myositis causes chronic
inflammation in your muscles — swelling that comes and goes over a long
time. Eventually, this inflammation makes your muscles feel weak. If you
have polymyositis, you may have inflammation in multiple muscles at the
same time. It usually affects the muscles on or near thecenter of your body,
including in your:
Arms Hips and thighs.
Chest.
Back.
Abdomen.
Neck.

SYMPTOMS AND CAUSES

The most common polymyositis symptoms include:

Muscle weakness (especially in your shoulders and hips).

Muscle pain and tenderness.
Trouble swallowing (dysphagia).
Difficulty talking.
Trouble breathing or shortness of breath (dyspnea).
Fatigue (feeling tired all the time).
Joint pain.
Fever.
Stiffness (especially right after you wake up in the morning). Weight loss.

Another Term: Polymyositis is also known as idiopathic

inflammatory
myopathy.

SYMPTOMS AND CAUSES

The most common polymyositis symptoms include:
Muscle weakness (especially in your shoulders and hips).
Muscle pain and tenderness.
Trouble swallowing (dysphagia).
Difficulty talking.
Trouble breathing or shortness of breath (dyspnea).
Fatigue (feeling tired all the time).
Joint pain.
Fever.
Stiffness (especially right after you wake up in the morning) weight loss.

ETIOLOGY :
The exact cause is unknown, but it's believed to be an autoimmune disorder
where the body's immune system mistakenly attacks healthy muscle tissue.
You’re more likely to develop polymyositis if you have other autoimmune
diseases, including:

Lupus.
Rheumatoid arthritis.
Scleroderma.
Some viral infections can trigger polymyositis, including:
COVID-19.
Influenza (the flu).
The common cold.
HIV.

EPIDEMIOLOGY:
Polymyositis is an uncommon disease. It affects both men and women, but
is more common in women. It can occur at any age, but is most common
between 50 and 70 years
old.

The overall prevalence is estimated at 1 per 100,000. It is more common in

black patients than in white patients.

RISK FACTORS:

Autoimmune diseases: People with other autoimmune diseases may have

an increased risk.
Age: While it can occur at any age, it's more common in individuals aged 50
to 70.
Sex: People assigned female at birth (AFAB) are twice as likely to have
polymyositis compared to people assigned male at birth (AMAB).

DIAGNOSIS AND TEST:

Blood tests: Elevated levels of muscle enzymes (like creatine kinase) can
indicate muscle damage.
Other blood tests may be done to check for other autoimmune markers.

Electromyography (EMG): This test measures the electrical activity of

muscles.

Magnetic Resonance Imaging (MRI): This imaging technique can help

visualize muscle inflammation.

Muscle biopsy: A small sample of muscle tissue is taken and examined

under a microscope to look for signs of inflammation and damage.

MANAGEMENT AND TREATMENT

Treatment:
The primary goal of treatment is to reduce inflammation and muscle
weakness. Treatment often involves a combination of medications and
therapies.

Medications:

Corticosteroids: These medications can help reduce inflammation.

Immunosuppressants: These medications help suppress the immune
system.Other medications: Depending on the individual's needs, other
medications may be used.

MANAGEMENT AND TREATMENT

Management:

Physical therapy :can help improve muscle strength and function.

Occupational therapy can help with activities of daily living.

Regular exercise and a healthy diet are important for overall health
and well-being.

ACID MALATASE
DEFICIENCY

ACID MALATASE
DEFICIECY
Acid maltase deficiency (AMD) is a rare genetic disorder characterized by a
deficiency of the lysosomal enzyme acid-α-glucosidase (GAA), leading to
glycogen build up within the lysosomes. This buildup occurs in the cells of
your organs and tissues, especially your heart and skeletal muscles,causing
them to break down.

Another Terms:
Pompe disease and Glycogen storage disease type
II (GSD II).

Etiology:
Pompe disease is caused by mutations in the GAA gene, which codes for the
acid-α-glucosidase enzyme.

Pathophysiology:
The deficiency of GAA prevents the breakdown of glycogen, a complex
sugar, in lysosomes (cellular compartments). This leads to an accumulation
of glycogen, particularly in skeletal and cardiac muscles, causing muscle
weakness and other complications.

RISK FACTORS:

Genetic Inheritance:
Pompe disease is an autosomal recessive disorder, meaning both
parents must carry a copy of the mutated GAA gene for their child to
inherit the condition.
Carrier Status:
Individuals who carry one copy of the mutated GAA gene are carriers
and can pass the gene to their children, but they do not typically
experience symptoms.

SIGNS AND SYMPTOMS:

Classic Pompe Disease (Infantile Form):

Appears soon after birth
Characterized by:
Hypertrophic cardiomyopathy (enlarged heart muscle)
Cardiorespiratory failure
Generalized muscle weakness (floppy infant syndrome)
Non-Classic Pompe Disease (Late-Onset Form):Appears later in childhood or
adulthood
Characterized by:
Progressive muscle weakness
Delayed motor skills (e.g., rolling over, sitting)
Cardiomegaly (enlarged heart)

DIAGNOSTIC TOOLS:
Measurement of α-glucosidase activity in dried blood spots: This
is essential for diagnosis.

Genetic testing: To confirm the diagnosis and identify the specific mutation
in the GAA gene.
Muscle biopsy: To examine muscle tissue for glycogen accumulation.
Treatment and Management / medication:

Enzyme Replacement Therapy (ERT):

The primary treatment for Pompe disease involves regular infusions of

alglucosidase alfa (Lumizyme), a man-made version of the GAA enzyme.

Symptoms Management:

Treatment also focuses on managing symptoms and complications, such as

respiratory support, nutritional support, and physical
therapy.

No cure:

While ERT can reduce or slow the progression of the disease, there is
currently no cure for Pompe disease.