Diagnosis: Pompe Disease

Complaints:

 Muscle weakness
 Difficulty in walking
 Myalgia(a yr ago)  muscle pain
 Frequent muscle cramps progressed to difficulty in walking  waddling gait  diff. climbing in stairs and
walking
 Frequent falls, unusually clumsy
 Sob, fatigue w/ mod exercise

Others:

 Born via normal delivery

 3rd and only boy
 Active child

1. To explain the normal structure and function of cell organelles.

 Cell is the basic building block of all living cells
 A cell contains the body’s hereditary material.
 It provides structure for the body, converts nutrients to energy and other special function.
 An alteration of the cell can damage its function.

Nucleus contains the cell’s hereditary (DNA) information and controls the cell’s growth and
reproduction.
Lysosome – these membranous sacs of enzymes recycle the cell’s organic material by digesting
cellular macromolecules. It contains Acid Alpha glucosidase enzyme.

GENE
 Gene is a basic functional and physical unit of hereditary.
 Hereditary is a process where one parent passes their genes to their offspring.
 Genes is made up of DNA. Every child inherits genes from their biological parents and
turned into specific trait.
2. Define Pompe disease and explain the physiologic function of the cell that is
impaired in this disease condition.
POMPE DISEASE / Glycogen Storage Disease Type II
 Autosomal recessive metabolic disorder (both parents are carriers)
 Accumulation of Glycogen in the Lysosome due to the deficiency of lysosomal acid alpha
glucosidase enzyme
 It results from the deficiency/mutation of an enzyme Acid Alpha Glucosidase (GAA)/ Acid
Maltase , ( chromosome 17 ) which breakdown complex sugar (glycogen) in the body
 damages the muscles and nerves cells throughout the body.
 When body can’t make protein that breakdown glycogen
 Defect in Lysosomal Metabolism
 A rare genetic disorder where the body cannot breakdown complex sugars (glycogen)
and it is stored in the cells which affects organs, tissues and muscle.
 Build-up of Glycogen causes :
 Myopathy ( muscle weakness ) – which affects tissues ( heart, skeletal muscle and nervous
tissue
 The GAA enzyme is found in all tissues, and continuous accumulation of glycogen due to a
deficiency in this enzyme causes lysosomes to swell and rupture, resulting in cellular damage
(Fig. 1). An accepted mechanism of pathophysiology is that this in turn leads to progressive
degeneration of skeletal, respiratory, and cardiac muscles, eventually resulting in loss of
function.  In the severe form of the disease, glycogen accumulation in liver tissue in addition
to cardiac and respiratory muscles. This leads to cardiomegaly, hepatomegaly, elevation of
liver enzymes, and death due to cardiorespiratory failure. In milder forms of the disease,
glycogen accumulation predominantly in skeletal muscles results in progressive weakness.
3. To correlate laboratory results with the clinical manifestation and other findings on
physical examination that occur in patients with Pompe disease.
>>>> LATE ONSET - ADULTHOOD
There are 3 types of Pompe :
1. Classic infantile-onset  appears within few months of birth.
2. Non-classis infantile onset  appears about 1 year of age.
3. Late-onset  appears later in a child’s life, even teens or adulthood.
Who gets POMPE DISEASE?
 It is inherited from parents (inherited 1 copy of defective gene who can be asymptomatic).
 It is a very rare disorder.
 Parents both carry defective gene.
 SYMPTOMS: depends when the disease presented

CLASSIC ONSET: NON-CLASSIC LATE ONSET –

 Few months old
 Weak muscle
 Poor Muscle tone
 Enlarged liver
(Hepatomegaly)
 Failure to gain
weight and grow
(failure to thrive)
 Trouble breathing
 Feeding Problems
 Infections in the
Respiratory
System
 Problems with hearing
ONSET ADULTHOOD
 1 year old  10 years old and
above
 Motor skills delayed  Legs and trunk
 (sitting/rolling over ) get steadily weak
 Muscles get  Breathing problems
steadily weak  Enlarged Heart
 Hepatomegaly  Increasing difficulty in
 Breathing walking
problems  Muscle pain over large
area
 Loss of ability to
exercise
 Falling often
 Lung infection
 Losing weight
 Morning headache
 Difficulty in swallowing
 Arrythmia

DIAGNOSTIC TEST
 Complete patient and family history
 Blood sample for enzymes to be studied and counted – Confirmation ( DNA Testing )
 Breathing test to measure Lung Capacity ( Pulmonary Function Test )
 Electromyography ( how well muscles work ) – MRI
 Heart Studies ( X-rays, Electrocardiogram, Echocardiogram )
 Sleep Studies ( respiratory breathing problem disturbance )
 Prenatal Diagnosis for pregnant women who is at risk. ( amniocentesis) – screen for developmetal
 abnormalities in a fetus

LABORATORY TEST
SGPT/ALT (liver test) – increase Creatinine
Kinase
 CK-BB – brain
 CK-MB - cardiac and skeletal muscle
 CK-MM- muscular injury Troponin –
increase
 Protein found in skeletal and heart muscle fibers that regulate contraction Myoglobin –
increase in blood when injury to muscle occur.
 Protein found in heart and muscle.

COMPLICATIONS – DEATH (absence of functional ACID ALPHA-GLUCOSIDASE)

 Respiratory problems (Respiratory Failure)
 Heart Problem (Cardiorespiratory Failure)
 Muscle Weakness
 Hyperlordotic = excessive spine curvature in the lower back.
 = C-shaped lower back in the LUMBAR region.

4. To discuss the physiologic basis of management of Pompe disease.

TREATMENT
Enzyme Treatment Therapy (ERT) – for all patient
Alglucosidase Alfa Intravenously
 genetically engineered enzyme
 act as natural occurring: Alfa glucosidase enzyme

MANAGEMENT
Infants who present with Pompe disease in the earlier phases of the disease generally present
with severe ventricular hypertrophy with or without left ventricular outflow tract obstruction and
normal or even hyperdynamic left ventricular EF. In the presence of LV outflow tract obstruction,
the use of digoxin, other inotropes, diuretics, and afterload reducing agents such as ACE-
inhibitors may exacerbate the left ventricular outflow tract obstruction.
CARDIOLOGY RECOMMENDATIONS
 Chest x-ray at regular intervals (see pulmonary recommendations).
 Obtain an initial echocardiogram to evaluate the extent of cardiomyopathy, of regular intervals.
 Medical management may be useful based on stage of cardiomyopathy.
 Avoid drastic changes in fluid status, either through dehydration or fluid overload.
 Obtain a twenty-four hour ambulatory ECG at baseline and regular intervals as patients are at risk
for life-threatening arrhythmias.
  Monitor for arrhythmias, including in patients on ERT.
Addressing impaired secretion clearance due to weakened cough is critical to maintaining
optimal functional status. Both manual and mechanical techniques used in treating other
neuromuscular. Liberal use of bronchodilators should be used in conjunction with these airway
clearance techniques and assisted coughing maneuvers (i.e., The Cough Assist In-Exsufflator)
to maximize the patient’s pulmonary toilet care. Inspiratory muscle training may also be
important. Bronchodilators and steroids (both inhaled and/or oral) can be useful when an
asthmatic process is present. If there is underlying cardiomyopathy, the use of selective beta
agonists (e.g., levalbuterol) may be recommended. All pulmonary infections should be
aggressively treated. Supplemental O2 (either nocturnal or continuous) can be used to treat
hypoxia, provided that hypoventilation is not present.
PULMONARY RECOMMENDATIONS
 Clinical assessment of respiratory status, both asleep and awake, should be performed at each
medical visit.
 When feasible, assessment of pulmonary function and gas exchange should be performed at
diagnosis, annually, and at every visit or with changes in patients’ clinical condition.
 Chest radiographs should be obtained upon diagnosis and when clinically indicated.
 Polysomnography should be performed upon diagnosis and when clinically indicated in infantile
and late onset Pompe disease.
 Maximizing clearance of airway secretions should routinely be performed.
 Assessment of respiratory function during sleep needs to be made whenever the patient
complains of daytime sleepiness, unexplained fatigue or has observed apneas during sleep, or
when vital capacity falls below 40–50% predicted.
 Supplemental oxygen and/or noninvasive positive pressure ventilation should be prescribed
based on underlying ventilatory abnormalities such as hypoxemia, obstructive sleep apnea, and
hypoventilation. Treatment modality should be based on a firm diagnosis of the type of
respiratory events seen during sleep.
 All pulmonary infections should be aggressively managed.
For patients with late-onset Pompe disease, the goal is intended to manage
1) the increasing accumulation of glycogen and
2) the increase in amino acid utilization

GASTROINTESTINAL/NUTRITION RECOMMENDATIONS
 Obtain videofluoroscopic swallowing assessment and evaluation for GE reflux to guide
management of feeding (oral/gavage feeding) at baseline and as clinically indicated.
 Provide oral stimulation and non-nutritive sucking for infants who are nonoral feeders.
 Monitor growth parameters carefully.
 Provide adequate nutrition (high protein consisting of 20–25% protein) with attention to vitamins
and minerals.
 Encourage appropriate exercise in consultation with a physical therapist with experience in
Pompe disease.
Rehabilitation management of Pompe disease
 comprehensive and preventative, based on an understanding of the pathokinesiology of
disease progression and on individual assessment.

 It should optimize and preserve motor and physiological function, prevent or minimize
secondary complications, promote and maintain the maximum level of function, and
maximize the benefits of ERT and other therapies when they become available.

 Rehabilitation services should include physical therapy, occupational therapy, speech

therapy, respiratory therapy, orthopedics, early intervention/educational/vocational
rehabilitation and independent living services, and the use of adaptive equipment,
assistive technology, and orthotic intervention where indicated.

 Rehabilitation related to respiratory and pulmonary issues are discussed within those
sections of this guideline.

 Management of feeding as relates to oral motor function is addressed in the

gastrointestinal/nutrition section have observed that a high protein-low carbohydrate diet
plus aerobic exercise, can be beneficial to some of these patients (see cautions on limits
of exercise in the Musculoskeletal/Functional/Rehabilitation section).

 The rationale to this form of therapy is an attempt to decrease glycogen deposition,

increase muscle fatty acid utilization, and at the same time compensate for the
increased amino acid oxidation that has been shown to occur in Pompe disease