Pompe disease

Pompe disease is an autosomal-recessive lysosomal glycogen-storage disorder caused by deficient acid alpha-glucosidase (GAA) activity from biallelic pathogenic variants in GAA. Glycogen accumulation primarily injures skeletal, respiratory, and cardiac muscle. Infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD) differ in cardiac involvement, presentation, monitoring, and treatment planning.1

Time-critical and urgent safety

An out-of-range Pompe newborn screen is not a diagnosis, but it requires prompt confirmatory testing and metabolic referral. Confirmed IOPD is time-critical because cardiomyopathy and respiratory or feeding weakness can progress rapidly and disease-modifying treatment is most effective when started early.1

Call emergency services for blue or gray color, severe breathing difficulty, fainting with poor recovery, inability to clear secretions, or acute feeding failure with reduced alertness. Promptly report new orthopnea, morning headaches, weak cough, breathing pauses during sleep, declining voice endurance, or recurrent chest infections; respiratory muscle weakness can be clinically significant before daytime shortness of breath.1

Infantile and late-onset patterns

IOPD presents during infancy with cardiomyopathy. Features may include hypotonia, generalized weakness, enlarged or thickened heart muscle, feeding difficulty, poor growth, macroglossia, and respiratory distress.1

LOPD includes infant presentations without cardiomyopathy and later presentations across childhood or adulthood. It more often presents with limb-girdle, trunk, neck, or diaphragmatic weakness, exercise intolerance, gait change, scoliosis, sleep-disordered breathing, or respiratory failure. Onset and progression vary. Cognition is not inherently impaired by Pompe disease.1

Screening and diagnosis

Newborn screening measures GAA activity in a dried-blood spot. Low screening activity can result from pseudodeficiency and requires confirmation. Diagnosis uses deficient GAA activity in leukocytes or another appropriate tissue and/or biallelic pathogenic or likely pathogenic GAA variants in a person with a positive screen or compatible features. A variant of uncertain significance does not establish the diagnosis.1

Evaluation determines cardiac, respiratory, swallowing, hearing, motor, and nutritional involvement. Muscle biopsy is not automatically required when biochemical and molecular testing establish the diagnosis. Family testing and recurrence counseling should use the confirmed variants with a genetics professional.1

Disease-modifying and supportive care

Enzyme-replacement therapy (ERT) is established disease-modifying treatment for Pompe disease. Several approved ERT products or combinations now have different age, weight, phenotype, prior-response, administration, and monitoring criteria. ERT improves important outcomes but is not a cure, and residual or progressive muscle, respiratory, hearing, or orthopedic concerns can remain.13

For IOPD, cross-reactive immunologic material (CRIM) status and antibody risk affect treatment planning; some people need specialist-directed immune-tolerance treatment around ERT initiation. These decisions are urgent but cannot be made from a general page. Infusion reactions, product selection, switching, and stopping criteria require a Pompe-experienced team.13

Ongoing care may include cardiology, respiratory and sleep medicine, neuromuscular and metabolic care, hearing, nutrition, speech-language pathology, rehabilitation, and genetics. Exercise, energy conservation, ventilation, cough support, mobility equipment, and positioning require direct assessment and monitoring rather than a disease-stage prescription.

Swallowing and communication

Feeding and swallowing assessment should consider weak suck or chewing, coughing or choking, nasal regurgitation, prolonged meals, respiratory symptoms, fatigue, weight and hydration, posture, and secretion clearance. Texture, pacing, positioning, equipment, and tube-feeding decisions require direct assessment coordinated with respiratory and nutrition care.1

Speech may become soft, short-phrased, or less reliable with facial, bulbar, or respiratory weakness. Language, literacy, and cognition are generally available for communication. Preserve the person's usual language and decision-making role and reduce effort before assuming a cognitive barrier.

AAC can be temporary, part-time, or long-term. Options include writing, alphabet boards, stored messages, text-to-speech, partner-assisted scanning, switches, and speech-generating systems. Trial access from current hand function, posture, fatigue, respiratory support, hearing, and vision. Include urgent breathing, suction, positioning, and pain messages, train partners, and maintain a low-tech backup.4 For evaluation, trials, funding, and implementation, use the AAC device acquisition guide.

Coding

• ICD-10-CM E74.02: Pompe disease.

The code does not distinguish IOPD from LOPD, newborn-screening status, treatment status, or current cardiac and respiratory involvement. Code associated conditions only when documented and supported by local rules.5

Sources

1. Leslie et al. Pompe Disease, GeneReviews — current phenotype definitions, screening, diagnosis, ERT, CRIM, surveillance, and genetics (updated 2025).
2. MetabERN clinical pathway recommendations for Pompe disease — current diagnosis, treatment, and multidisciplinary follow-up pathway (2024; PMID 39482698).
3. US Food and Drug Administration: cipaglucosidase alfa-atga and miglustat approval record — example of phenotype, age, weight, and prior-response limits on current treatment indications.
4. American Speech-Language-Hearing Association: Augmentative and Alternative Communication — individualized, multimodal AAC assessment.
5. Centers for Medicare & Medicaid Services: FY2026 ICD-10-CM definitions — E74.02 descriptor.

Review boundary

This page cannot diagnose Pompe disease, interpret a newborn screen, select or monitor ERT, determine CRIM or immune-tolerance treatment, or remotely assess cardiac, respiratory, or swallowing risk. Emergencies require immediate local assessment. Treatment, ventilation, diet, exercise, equipment, mobility, and communication decisions require direct review with qualified teams and the person or family.