A CRIM-negative Pompe Case Receiving Enzyme Replacement Therapy with a Successful Immunotolerance Regimen
2Hacettepe University Faculty of Medicine Department of Pediatrics Pediatric Immunology Unit, Turkiye
3Hacettepe University Faculty of Medicine Department of Pediatrics Pediatric Rheumatology Unit, Turkiye
4Ankara Etlik City Hospital Complex Children's Hospital Pediatric Metabolic Diseases Unit, Turkiye
Background: Pompe disease or Glycogen Storage Disease Type II (OMIM: #232300) is the first autosomal recessive metabolic disease due to lysosomal acid α-glycosidase (GAA) enzyme deficiency. During GAA enzyme deficiency, glycogen accumulates in intracellular lysosomes and causes disorders in the organs and tissues where it accumulates, especially in muscle tissue. There are two forms of the disease, early (infantile) and late-onset (juvenile-adult). Significant improvement in symptoms and prognosis has been reported in patients followed up with enzyme replacement therapy (ERT). CRIM positivity in patients receiving ERT indicates that the patient will not develop an immunological reaction to the enzyme and it is important in terms of enzyme therapy. In a study that examined the CRIM test results in relation to the ERT response, life span, heart function and motor development in Pompe disease patients, it was reported that CRIM negativity was associated with poor prognosis. The CRIM test in our case was negative and an immunotolerance regimen was given before ERT.
Case: A 2-month-old female patient presented to our clinic due to hypotonia, elevated creatine kinase and hypertrophic cardiomyopathy. When she was one month old, her mother had taken her to a different general pediatric outpatient clinic because of decreased movements and she was diagnosed with hypertransaminasemia. Echocardiography showed hypertrophic cardiomyopathy and her serum creatinine kinase was 477 U/L (N150). Her mother and father were consanguineous but originated from the same village. Her GAA activity was low at 0.16 μmol/hour/L, so a preliminary diagnosis of Pompe disease was considered. The diagnosis was confirmed by the identification of a homozygous c.2646+2TA mutation in the GAA gene but the CRIM test was negative. After consultation with the immunology and rheumatology departments, the patient was treated with 4 cycles of subcutaneous methotrexate at a dose of 0.6 mg/kg before ERT, followed by Alglucosidase alfa at a dose of 30 mg/kg for 2 weeks and 1 mg oral rescue folic acid 2 days after the methotrexate. Immunomodulation was discontinued as the patient did not show an increase in the Alglucosidase alfa IgG Ab titer.
Results: The patient’s Alglucosidase alfa IgG Ab titer remained stable under ERT and their cardiac findings improved. The patient is still being followed under ERT without any problems.
Discussion: CRIM negativity is associated with a poor prognosis in Pompe patients. Many immunotolerance protocols have been reported with mixed results including combinations of different agents such as rituximab, intravenous immunoglobulin, and methotrexate. In our case, successful immunotolerance was achieved with a single agent.
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