title: Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report.
abstract: Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m(2) (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.
authors.affiliation: Division of Metabolic Diseases, Department of Paediatrics, University Hospital Padua, Via Giustiniani 3, 35128 Padua, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Del Rizzo
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.forename: Alessia
authors.initials: A
authors.lastname: Cerutti
authors.forename: Chiara
authors.initials: C
authors.lastname: Cazzorla
authors.forename: Ornella
authors.initials: O
authors.lastname: Milanesi
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Nascimbeni
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Laura
authors.initials: L
authors.lastname: Giordano
authors.forename: Andrea
authors.initials: A
authors.lastname: Bordugo
authors.forename: Alberto B
authors.initials: AB
authors.lastname: Burlina
mesh_terms: D001706:Biopsy; D001919:Bradycardia / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009202:Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D004252:DNA Mutational Analysis; D042241:Early Diagnosis; D056947:Enzyme Replacement Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020125:Mutation, Missense; D010641:Phenotype; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases