Pompe Diasese –A Review

 

Mrs Purohit Saraswati, Mrs. Mamatha M, Mrs. Sunith PS, Mrs. Rashmi P

Asst Lecturer, J.S.S College of Nursing, Ramanuja Road., Mysuru-570004

*Corresponding Author E-mail: saruswati28@gmail.com

 

ABSTRACT:

Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally. Pompe disease, also known as glycogen storage disease type II. The disease is caused by mutations in the gene that instructs the body to make an enzyme called acid alpha-glycosidase (GAA). Patients with Pompe disease have deficient lysosomal enzyme acid alpha-glycosidase (GAA) activity, which catalyses the breakdown of glycogen to glucose in the lyososome.1 Clinically it is classified into 3 types namely Infantile-onset Pompe disease, Non-classic infantile-onset Pompe disease and Late or adult onset Pompe disease. Diagnostic test is the measurement of acid alpha-glucosidase (GAA) enzyme activity. Pompe disease management can be done based on its manifestations and complications.

 

KEY WORDS: acid alpha-glycosidase, lysosome, Heterozygote

 


INTRODUCTION:

Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally. Pompe disease is a rare, progressive, and often fatal muscular disease. The underlying pathology is a deficiency of the enzyme acid alpha-glucosidase (GAA) that hydrolyzes lysosomal glycogen. Pompe disease is a single disease which manifests as a clinical spectrum that varies with respect to age at onset, rate of disease progression, and extent of organ involvement.2

 

What is Pompe Disease:

Pompe disease, also known as glycogen storage disease type II, is an inherited disorder whose primary symptom is progressive weakness in the muscles used for mobility and breathing. In infants with Pompe disease, the heart muscles are often severely affected as well.

 

CAUSES:

Pompe disease, also known as glycogen storage disease type II or acid maltase deficiency, is a rare genetic disorder that results in profound muscle weakness. The disease is caused by mutations in the gene that instructs the body to make an enzyme called acid alpha-glucosidase (GAA).3

 

What Organelle does Pompe Disease Affect in a Cell?:

Patients with Pompe disease have deficient lysosomal enzyme acid alpha-glucosidase(GAA) activity, which catalyses the breakdown of glycogen to glucose in the lyososome. Without sufficient GAA activity, massive amounts of glycogen can accumulate in the lysosome, causing distention of this organelle.

 

Clinical Manifestations: 4

Infantile onset<12 months

Late onset >12months

Head lag

Morning headache

Enlarged tongue

Gait abnormality

Respiratory insufficiency

Day time somnolence

Delayed motor development

Shortness of breath

Muscle weakness

Scapular winging

Cardiomegaly

scoliosis

organomegaly

Low back pain

 

Muscle weakness

 

Classification of Pompe Disease:

Clinical Classification:

1) Infantile-onset Pompe Disease:

Classic infantile-onset Pompe disease has a reported incidence of 1 in 100,000 and will usually present in the first two to six months of life with hypotonia and muscle weakness, feeding difficulties and failure to thrive, respiratory distress or infections and cardiac problems.

 

2) Non-Classic Infantile-onset Pompe Disease:

This variant will usually present within the first year of life with motor developmental delay and weakness. Cardiomegaly is less a feature, and cardiac involvement is not present in some definitions of non-classic infantile-onset Pompe disease. The rate of clinical progression is slower in these children and without treatment, death will usually occur in childhood as a result of respiratory insufficiency.

 

3) Late or Adult onset Pompe Disease:

This variant can present at any age, although typically an earlier presentation is associated with more severe symptoms. Clinical features include proximal muscle weakness that progresses slowly, and the involvement of the respiratory muscles and diaphragm. A lower limb weakness, poor exercise tolerance and fatigue are usually present, and affected patients may become wheelchair bound in later life. Orthopnoea, sleep apnoea, and respiratory failure may also be present.5

 

DIAGNOSTIC TESTS:

Measurement of acid alpha-glycosidase (GAA) enzyme activity is diagnostic. GAA is the only gene in which mutation is known to cause GSD II.6

 

MANAGEMENT:

Treatment of manifestations:

Management guidelines from the American College of Medical Genetics: individualized care of cardiomyopathy as standard drugs may be contraindicated and risk for tachyarrhythmia and sudden death is high; physical therapy for muscle weakness to maintain range of motion and assist in ambulation; surgery for contractures as needed; nutrition/feeding support. Respiratory support may include inspiratory/expiratory training in affected adults, CPAP, BiPAP and/or tracheostomy.

 

Prevention of Primary Manifestations:

Begin enzyme replacement therapy (ERT) with Myozyme or Lumizyme (alglucosidase alfa) as soon as the diagnosis is established. Infants at high risk for development of antibodies to the therapeutic enzyme are likely to need an immunomodulatory protocol early in the treatment course. In the pivotal trial, a majority of infants in whom ERT was initiated before age six months and before the need for ventilatory assistance demonstrated improved survival, ventilator-independent survival, improved acquisition of motor skills, and reduced cardiac mass compared to untreated controls. In affected individuals with late-onset disease, ERT may stabilize ventilatory function and motor ability, measured by six-minute walk and upright pulmonary function testing. ERT can be accompanied by treatable infusion reactions as well as anaphylaxis.

 

Prevention of Secondary Complications:

Aggressive management of infections; keeping immunizations up to date; annual influenza vaccination of the affected individual and household members; respiratory syncytial virus (RSV) prophylaxis (palivizumab) in the first two years of life; use of anesthesia only when absolutely necessary.

 

Surveillance:

Routine monitoring of respiratory status, cardiovascular status, musculoskeletal function (including bone densitometry), nutrition and feeding, renal function, and hearing.

 

Agents/circumstances to avoid:

Digoxin, ionotropes, diuretics, and after load-reducing agents, as they may worsen left ventricular outflow obstruction in some stages of the disease; hypotension and volume depletion; exposure to infectious agents.

 

Evaluation of relatives at risk:

Evaluate at-risk sibs by GAA enzyme activity or molecular genetic testing (if the pathogenic variants have been identified in an affected family member) to permit early diagnosis and treatment with ERT.

 

Genetic Counseling:

GSD II (Pompe disease) is inherited in an autosomal recessive manner. In most instances, the parents of a proband are heterozygote and thus carry a single copy of a GAA pathogenic variant. Heterozygote’s (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Historically, children with classic infantile Pompe disease have not survived to reproduce, whereas many individuals with later-onset disease survive into their 50s and 60s. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.7

 

CONCLUSION:

Pompe disease is a rare, progressive, and often fatal muscular disease. The underlying pathology is a deficiency of the enzyme acid alpha-glucosidase (GAA) that hydrolyzes lysosomal glycogen. Pompe disease is a single disease which manifests as a clinical spectrum that varies with respect to age at onset, rate of disease progression, and extent of organ involvement.

 

REFERENCES:

1.     https://ghr.nlm.nih.gov/condition/pompe-disease:accessed on 18/10/2016

2.     https://rarediseases.org/rare-diseases/pompe-disease/:cited on 25/10/2016

3.     https://www.counsyl.com/services/family-prep-screen/diseases/pompe-disease/accesses on 10/11/2016

4.     http://www.webmd.com/a-to-z-guides/pompe-disease#1/cited on 15/11/2016

5.     http://www.nature.com/gim/journal/v8/n5/abs/gim200650a.html cited on 20/11/2016

6.     https://www.ncbi.nlm.nih.gov/books/NBK1261/ accessed on 25/11/2016

7.      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110959/cited on 01/12/2016

 

 

 

 

Received on 22.08.2016          Modified on 29.08.2016

Accepted on 21.12.2016          © A&V Publications all right reserved

Int. J. Adv. Nur. Management. 2017; 5(1): 82-84.

DOI:  10.5958/2454-2652.2017.00018.X