Researchers presented the case of a patient with late-onset Pompe disease (LOPD) with an identified compound heterozygous mutation, as published in Frontiers in Neurology

The case study details a 22-year-old patient who was hospitalized for progressive dyspnea and ambulatory weakness for 2 months. The neurological team noted that the patient had poor chest expansion and decreased tendon reflexes in her upper and lower extremities. She had varying degrees of weakness in the flexor and extensor muscles of the wrist and the forearm, as well as the intrinsic muscles of the feet (none were lower than three-fifths). 

Her laboratory results demonstrated the following: 

Continue Reading

  • Elevated levels of creatine kinase-MB isoenzyme: 51.4 IU/L 
  • Elevated lactate dehydrogenase: 392.9 U/L 
  • Creatine kinase, alanine aminotransferase, and aspartate aminotransferase levels were within the normal range. 

In addition, her further blood investigations revealed the following: 

  • Elevated red blood cell count: 7.37x 1012/L 
  • Elevated hemoglobin: 174.3 g/L 
  • Elevated hematocrit: 59.8% 
  • Elevated N-terminal probrain natriuretic peptide: 2038 pg/ml 

Upon the patient’s first night of hospitalization, her dyspnea worsened and she developed blurred consciousness, restlessness, and urinary incontinence. Urgent head computerized tomography (CT) scan revealed multiple overdue strip high-density shadows presented in the sulfide of the bilateral cerebral hemispheres.

Chest CT revealed bilateral pleural effusion and inflammation in the lungs. Chest x-ray demonstrated an increased cardiothoracic ratio and the presence of inflammation in the lungs. Her blood gas revealed a pH of 7.057 and a pCO2 of 18.4 kPa and she was therefore started on ventilator support.

Read more about Pompe disease etiology

Acid alpha-glucosidase (GAA) activity in the patient was found to have decreased to 9.77 nmol/1 h/mg, which was insufficient for a diagnosis of GAA activity deficiency. Her physicians next performed a muscle biopsy of her left quadriceps with written consent. Genetic studies revealed 2 compound heterozygous mutations at c.1411_1414del (p.Glu471ProfsTer5) in exon 9 and c.2238G>C (p.Trp746Cys) in exon16 in the patient.

The patient was diagnosed with myasthenia gravis (MG) and started on gamma globulin (0.4 g/kg x 5 days) and methylprednisolone (500 mg/d x 3 days). Later tests ruled out a diagnosis of MG. A permanent tracheostomy was placed in view of the patient’s long-term need for a ventilator.

She was discharged with home ventilation support. Six months later, the patient’s condition improved enough for her to walk for about 15 minutes and she could choose not to use her ventilator at rest during the daytime, as well as when dressing and showering herself.

“Among the heterozygous mutation, c.1411_1414del (p.Glu471ProfsTer5) was a rare and damaging mutation for LOPD,” the authors concluded. “We emphasized the importance of muscle biopsy and GAA gene analysis in diagnosing respiratory and ambulatory weakness.” 


Zhang H, Chen J, Zhu Y, Ma X, Zhong W. Case report: identification of compound heterozygous mutations in a patient with late-onset glycogen storage disease type II (Pompe disease)Front Neurol. 2022;13:839263. doi:10.3389/fneur.2022.839263