Pompe disease is an autosomal recessive condition with an incidence of around 1 in 40,000 in the general population, and is caused by a deficiency of the enzyme acid alpha-glucosidase. Clinical features occur due to the deposition and accumulation of glycogen within lysosomes, most notably those within the cardiac and skeletal muscles. The extent of this enzyme deficiency affects both the age of onset and severity of symptoms, and allows for clinical stratification into distinct subgroups.
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. Clinical examination and investigation will frequently reveal hypotonia and motor developmental delay, macroglossia, cardiomegaly, generalised hypertrophy, a murmur, cardiomyopathy, conduction disturbances (short PR interval with a broad QRS complex), respiratory distress and hepatomegaly (usually as a consequence of heart failure).
Children with classic infantile-onset Pompe disease will usually have a severe deficiency of the acid alpha-glucosidase enzyme .
Without treatment, these symptoms will progress rapidly and the hypertrophic cardiomyopathy may develop a left ventricular outflow tract obstruction or compress adjacent respiratory structures. These cardiac features together with significant weakness of the diaphragmatic and respiratory muscles will lead to death from cardiorespiratory failure within the first year of life.
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.
Unlike the infantile-onset forms of Pompe disease cardiac involvement is not a feature, although some adults have been reported to have arteriopathy which may be associated with raised blood pressure and occasionally aortic dilatation.
Those affected by late-onset Pompe disease will usually have a partial deficiency of the enzyme acid alpha-glucosidase (2 – 40% normal enzyme activity) .
Without treatment, morbidity and mortality occur mainly as a result of respiratory insufficiency and failure, with death occurring anytime from the third decade onwards.