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Título

POMPE DISEASE ENZYME REPLACEMENT THERAPY : A CASE REPORT

Apresentação do caso único

Female, 8 years old, born at term, cesarean section. Neonatal screening tests were normal. Parents are healthy and non-consanguineous. The brother is healthy and the sister died of cardiomyopathy. The mother was referred at 30 days of life with asthenia and cyanosis during breastfeeding. At 60 days of life, an echocardiogram was performed that diagnosed cardiomegaly and hypertrophic cardiomyopathy. Patient was hospitalized for investigation of cardiomyopathy. Electroneuromyography was performed that complies with a myopathic pattern. Laboratory tests were also performed, with deficiency of the enzyme alpha glucosidase (4.8). In addition, the genetic panel revealed heterozygous variation in the GAA gene and was caused by infantile Pompe disease. Frameshift mutation 17q25.3, NM-000152.4(GAA);c.525delT;p(GLu176Argfs0), and, missense variation NM- 000152-4(GAA): 1941c>G;p.(Cys647Trp). Neurological evaluation showed body hypotonia, deep reflexes were present and symmetrical. Enzyme therapy with Myozyme 20g/kg dose every 15 days was started. The patient maintained significant hypotonia without improvement in the evolution of cardiomyopathy and significant muscle weakness that worsened between 12-14 days after enzyme administration. It was decided to start weekly treatment with Myozyme, maintaining 20g/kg, resulting in significant clinical improvement. Currently, the patient is stable. Echocardiography revealed control hypertrophic cardiomyopathy secondary to Pompe disease with mild left ventricular hypertrophy, preserved systolic and diastolic function, and an ejection fraction of 70%. The electrocardiogram was normal, and the Holter monitoring showed mild isolated supraventricular extrasystoles.

Discussão

Pompe disease is a rare recessive genetic disease that results in glycogen storage related to defects in the enzyme acid alpha-glucosidase, or that leads to an intracellular accumulation of glycogen, especially in the muscles and heart. Two forms have been described: infantile and juvenile. Enzyme replacement therapy can help improve muscle tone and reduce glycogen storage in individuals with Pompe disease.

Comentários finais

Transitioning from biweekly to weekly enzyme replacement therapy demonstrated remarkable clinical improvement. There was stabilization of the hypertrophic cardiomyopathy, increased muscle tone, and improvement in quality of life, highlighting the effectiveness of adjusting the frequency of therapy to improve clinical benefits in the treatment of Pompe disease.

Referências

1. Kohler L, Puertollano R, Raben N. Pompe Disease: From Basic Science to Therapy. Neurotherapeutics. 2018 Oct;15(4):928-942. doi: 10.1007/s13311-018-0655-y. PMID: 30117059; PMCID: PMC6277280.
2. Meena NK, Raben N. Pompe Disease: New Developments in an Old Lysosomal Storage Disorder. Biomolecules. 2020 Sep 18;10(9):1339. doi: 10.3390/biom10091339. PMID: 32962155; PMCID: PMC7564159.

Palavras Chave

Pompe; enzyme replacement therapy; myopathy