Makindo Medical Notes

Pompe disease leads to the accumulation of glycogen in the lysosomes, causing damage to the heart, liver, and muscles.

About

• An autosomal recessive disorder.
• Classified as both a metabolic myopathy and motor neuron disease.
• Typically presents in infancy but can manifest in adults.

Mechanism

Aetiology

• Caused by a deficiency in the GAA gene, leading to a lack of acid alpha-1,4-glucosidase (acid maltase).
• This enzyme deficiency results in glycogen accumulation within lysosome-derived vacuoles in cells.
• Acid maltase normally breaks down glycogen into glucose; without it, glycogen builds up, leading to cell damage.

Clinical Features

• Infantile-onset: Presents with hypotonia (floppy baby), bulky muscles, and macroglossia.
• Massive cardiomegaly, often progressing to congestive heart failure.
• Hepatomegaly, but notably NO ketosis or hypoglycaemia.

Differential Diagnosis

• Duchenne Muscular Dystrophy: Similar muscle weakness but different etiology.

Investigations

• CK Levels: Elevated or normal.
• Abdominal Ultrasound: Shows hepatomegaly.
• Echocardiography: Demonstrates cardiomegaly.
• Liver Function Tests (LFTs): Elevated AST and LDH.
• Muscle Biopsy: Increased acid maltase activity and glycogen accumulation within lysosomes.
• Electron Microscopy: Confirms glycogen accumulation in vacuoles and cytoplasm.
• Serum acid maltase levels may be measured to confirm diagnosis.

Management

• The most severe forms of Pompe disease lead to death between the ages of 6 months and 2 years.
• Milder forms exist, with patients surviving into adulthood and having a better prognosis.
• Treatment with recombinant human enzyme alpha-glucosidase has shown evidence of benefit, helping improve outcomes in patients.