Dados do Trabalho

Título

POMPE DISEASE: THE CREATION OF A NEONATAL SCREENING PROTOCOL WILL MODIFY THE NATURAL HISTORY OF THE DISEASE

Apresentação dos casos

Case 1: A 5-month-old female infant, born at term with no previous hospitalizations and no known consanguinity. She was admitted to the hospital due to pneumonia. During the investigation, a chest X-ray revealed cardiomegaly. Further evaluation with an echocardiogram showed symmetric non-obstructive hypertrophic cardiomyopathy and a left ventricular mass index of 557 g/m². She was transferred to a reference center for pediatric cardiology evaluation. Upon admission, she was in fair general condition, and had normal cardiac and pulmonary auscultation. Notable developmental delays included lack of cervical support, hypotonia, global areflexia, absence of active movement in all four limbs despite painful stimuli, weak crying, and absence of the primitive plantar grasp reflex. During hospitalization, she developed respiratory failure, cardiorespiratory arrest, and ultimately died. Case 2: A 3-month-old male infant, born at term with no previous hospitalizations and no known consanguinity. He was admitted due to respiratory discomfort. A chest X-ray showed cardiomegaly, and an echocardiogram confirmed symmetric non-obstructive hypertrophic cardiomyopathy. Upon admission to the reference center, he exhibited developmental delays, absence of cervical support, hypotonia, and global areflexia. He also progressed to respiratory failure, cardiorespiratory arrest, and death during hospitalization. Both cases underwent genetic testing for Pompe Disease, which showed positive screening results with reduced activity of acid alpha-glucosidase. Further sequencing of the GAA gene revealed pathogenic mutations in homozygosity of the GAA gene.

Discussão

Both cases involve early-onset Pompe Disease, a lysosomal storage disorder inherited in an autosomal recessive pattern with an incidence of 1 in 40,000 live births. This condition leads to the accumulation of glycogen in tissues such as muscles and the liver. The infantile form of Pompe Disease is characterized by clinical manifestations including cardiomegaly, respiratory difficulties, and hypotonia. In Brazil, enzyme replacement therapy has been included in the Unified Health System (SUS) since 2006

Comentários finais

Despite being a rare disease, we emphasize the importance of establishing a neonatal screening protocol in the country for early diagnosis before the onset of clinical symptoms. This would facilitate timely treatment and potentially alter the natural history of the disease.

Referências

Hirschhorn R, Reuser A. Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In: The metabolic and molecular bases of inherited disease, Scriver C, Beaudet A, Sly W, Valle D (Eds), McGraw-Hill, New York 2001. p.3389.
Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999; 7:713.
Mechtler TP, Stary S, Metz TF, et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet 2012; 379:335.
Burton BK, Charrow J, Hoganson GE, et al. Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience. J Pediatr 2017; 190:130.
Raben N, Plotz P, Byrne BJ. Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med 2002; 2:145.
Orth M, Mundegar RR. Effect of acid maltase deficiency on the endosomal/lysosomal system and glucose transporter 4. Neuromuscul Disord 2003; 13:49.
Kroos M, Hoogeveen-Westerveld M, van der Ploeg A, Reuser AJ. The genotype-phenotype correlation in Pompe disease. Am J Med Genet C Semin Med Genet 2012; 160C:59.

Palavras Chave

pompe disease; lysosomal storage diseases; inborn error of metabolism