Pompe Disease: A Rare Genetic Disorder
Pompe disease is a rare inherited disorder caused by a deficiency or malfunction of the lysosomal enzyme acid alpha-glucosidase (GAA). Without this enzyme, glycogen builds up inside cells, especially in skeletal and respiratory muscles, the heart, liver, and nervous system. This accumulation leads to progressive muscle weakness and, if untreated, premature death from respiratory or cardiac failure.
The condition is also known as Glycogen Storage Disease Type II or Acid Maltase Deficiency.
Pompe disease symptoms can appear as early as infancy, including low muscle tone, delayed motor development, and skeletal abnormalities.
Clinical Forms
1. Infantile-Onset Pompe Disease (IOPD)
Symptoms appear within the first weeks of life, including:
- Muscle and motor issues: Generalized hypotonia (low muscle tone), delayed motor development, firm and rubbery muscles, calf hypertrophy, Gowers’ sign
- Cardiac problems: Hypertrophic cardiomyopathy, left ventricular outflow tract obstruction, conduction system abnormalities
- Respiratory issues: Respiratory failure requiring urgent intervention
- Other signs: Feeding difficulties, growth delay, hepatomegaly, macroglossia, hearing loss
- Progression: Without treatment, most infants die within the first year.
Early detection is sometimes possible prenatally, and symptoms after two months of age may be milder but still include hypotonia and delayed motor milestones.
2. Late-Onset Pompe Disease (LOPD)
Symptoms may appear from childhood to adulthood, often progressing slowly:
- Muscle weakness: Mainly proximal muscles; difficulty climbing stairs, rising from chairs, or raising arms
- Respiratory involvement: May worsen after anesthesia; chronic respiratory support often needed
- Other signs: Macroglossia, hepatomegaly (sometimes), lumbar hyperlordosis, scoliosis
- Impact on daily life: Adolescents may have reduced physical capacity; many adult-onset patients live normal lives for years before noticeable limitations
Late-onset Pompe disease can resemble limb-girdle muscular dystrophy.
Key Symptoms
- Progressive muscle weakness (proximal muscles first)
- Respiratory difficulties (shortness of breath, chronic insufficiency)
- Heart enlargement (hypertrophic cardiomyopathy)
- Feeding difficulties in infancy
- Growth delay
- Firm, rubbery muscles with calf hypertrophy
- Skeletal abnormalities (lumbar hyperlordosis, scoliosis)
- Macroglossia and hepatomegaly
Diagnosis
Diagnosis involves:
- Blood tests for enzyme activity
- Genetic testing for GAA mutations
- Muscle biopsy (glycogen accumulation in lysosomes)
- Imaging and EMG to evaluate muscle and heart involvement
- Monitoring serum creatine kinase (CK) and liver enzymes
Treatment
The only causal treatment is enzyme replacement therapy (ERT):
- Alglucosidase alfa: A recombinant version of GAA administered chronically
- Symptomatic management: Treat complications such as heart failure, respiratory insufficiency, and skeletal deformities
- Early treatment, especially in infantile-onset, significantly improves survival and quality of life
References