Pompe Disease

Pompe disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive lysosomal storage disorder from GAA mutations causing glycogen accumulation.

• Incidence 1 in 40,000.

• Infantile onset (IOPD): cardiomyopathy, hypotonia, death by 1 year without treatment. Late onset (LOPD): limb girdle weakness and respiratory failure from childhood to adulthood.

• Diaphragmatic weakness with orthopnoea is a distinctive feature.

• IOPD: floppy infant, macroglossia, hepatomegaly, hypertrophic cardiomyopathy, respiratory failure.

• LOPD: slowly progressive proximal weakness, trunk weakness, early respiratory involvement, scoliosis, fatigue, back pain.

• Rarely cerebral aneurysm.

• Reduced acid alpha glucosidase activity in dried blood spot, lymphocytes or fibroblasts (confirm with second tissue).

• GAA sequencing; CRIM status (infantile) by immunoblot.

• CK mildly raised (2 to 10 times), raised urinary Glc4 tetrasaccharide.

• Pulmonary function: supine drop in FVC over 10% suggests diaphragm weakness. ECG (short PR, large QRS), echocardiogram.

• Muscle biopsy with PAS positive vacuoles (usually not needed). Newborn screening where available.

• Enzyme replacement therapy: alglucosidase alfa 20 mg/kg IV every 2 weeks (40 mg/kg in infantile onset), avalglucosidase alfa 20 mg/kg every 2 weeks, cipaglucosidase alfa 20 mg/kg with miglustat 260 mg orally 1 hour before (LOPD).

• Start immediately in IOPD; immunomodulation (rituximab, methotrexate, IVIG) in CRIM negative infants to prevent antibody formation.

• Premedicate for infusion reactions (antihistamine, paracetamol, steroid); anaphylaxis preparedness.

• Respiratory support: non invasive ventilation, cough assist, vaccination.

• Physiotherapy, exercise, high protein diet; orthopaedic care.

• Cardiac care for infantile disease.

• Genetic counselling and sibling testing.