What is Pompe disease?
Pompe disease is a lysosomal storage disorder that occurs due to partial or complete deficiency of the enzyme acid α glucosidase. (Online Mendelian Inheritance in Man number -232300) This results in accumulation of the lysosomal glycogen in all cells of the body. However the clinical phenotype occurs mostly due to muscle involvement and it is also referred to as a metabolic myopathy. This disease has an autosomal recessive pattern of inheritance. It affects both, males and females and has an estimated frequency of 1 in 40,000 live births.
When do we suspect Pompe disease?
It presents with a continuous spectrum of disease phenotype from infancy to adulthood.
Classic early onset Pompe disease presents before 1 year of age with cardiac and skeletal muscle involvement. Most affected neonates present shortly after birth with rapidly progressive disease symptoms of
Late onset Pompe disease is a slowly progressive disease phenotype. The clinical features include
· Respiratory problems as the major cause of mortality
Therefore the spectrum of disease manifestations to alert for testing for Pompe disease
- Hypertrophic cardiomyopathy
- Motor developmental delay
- Proximal limb girdle muscle weakness – difficulty in climbing stairs, dancing, doing sports
- Respiratory problems with progression to ventilator use
- Affected siblings with similar phenotype
How is Pompe disease diagnosed?
High index of suspicion is important
1. Clinical suspicion based on the above-mentioned features – hypertrophic cardiomyopathy and hypotonia in infants and proximal limb girdle muscle weakness in older children and adults.
2. Elevated serum CK (creatine kinase) levels in infants and EKG evidence of short PR interval and large QRS complexes
3. Acid alpha-glucosidase (GAA) enzyme activity in blood (3 ml blood in heparin vacutainer) or dried blood spots.
4. Molecular analysis of GAA gene – 4 ml blood in EDTA vacutainer is required for this testing. It is also helpful to send the blood sample of the parents for carrier testing and confirmation of the mutations identified in the affected patient.
What are the treatment options available?
Enzyme Replacement Therapy (ERT) with recombinant Myozyme® (alglucosidase alfa) is available for treatment. Early diagnosis and initiation of definitive treatment with ERT facilitates a good response to therapy. The enzyme is given as an infusion once every 2 weeks. It is a safe modality with few infusion related reactions.
Supportive therapy in form of physiotherapy, cardiac management and regular monitoring for possible complications is also important.
Without definitive treatment like ERT, the disease course is progressive. Infantile onset Pome patients mostly die before the first year of life. The late onset patients develop respiratory failure and this is the commonest cause of mortality.
How to prevent the birth of a child with Pompe disease?
- Parents of a child with Pompe disease are carriers. They will never develop any disease manifestations.
- For a couple with one child with Pompe disease, or those who are identified to be carriers, there is a 25% risk of recurrence in each pregnancy.
- Prenatal diagnosis by chorionic villus sampling and molecular analysis for the familial mutation is performed at 11 weeks of gestation.
- Carrier testing by molecular analysis of siblings of the parents of an affected child should be offered. They have a 50% of being carriers.
When to contact a Medical Professional?
- When a diagnosis of Pompe disease is made
- When pregnancy is planned in a family with history of Pompe disease
Who to contact for more information?
- The Department of Health Research and Indian Council of Medical Research have constituted a National Task Force to perform a multicentric collaborative study at different research institutes across the country.
Lysosomal Storage Society of India - LSDSS
|PATIENT INFO ENGLISH|
|PATIENT INFO HINDI|
Dr Ratna Dua Puri
Sri Ganga Ram Hospital, New Delhi