RESUMEN
In previous years, the role of gastroesophageal (GE) ultrasound as a diagnostic tool in gastroesophageal reflux disease (GERD) has been disputed. Most authors believe that it is difficult to diagnose GERD without correlation studies between esophageal pathology and ultrasonographic signs. Indeed, there are many anatomic descriptions of the normal GE junction. The fact that GERD diagnosis was made by morphological studies was believed to be an incorrect deduction. We revisit the pathophysiologic data concerning the gastroesophageal junction and gastric function and review the data in the literature of the past 30 years.
Asunto(s)
Reflujo Gastroesofágico , Niño , Unión Esofagogástrica/diagnóstico por imagen , Reflujo Gastroesofágico/diagnóstico por imagen , Humanos , UltrasonografíaRESUMEN
BACKGROUND: Glycogenosis type II (GSDII or Pompe disease) is an autosomal recessive disease, often characterized by a progressive accumulation of glycogen within lysosomes caused by a deficiency of α-1,4-glucosidase (GAA; acid maltase), a key enzyme of the glycogen degradation pathway. To date, more than 326 different mutations in the GAA gene have been identified in patients with GSDII but the course of the disease is difficult to be predicted on the basis of molecular genetic changes. Studies on large informative families are advisable to better define how genetics and non genetics factors like exercise and diet may influence the clinical phenotype. METHODS AND RESULTS: In this study, we report on clinical, instrumental, and pathological features as well as on molecular analysis of a family with 10 out of 13 siblings affected by late-onset Pompe disease. Three mutations segregated in the family, two of which are novel mutations. Siblings showing a more severe phenotype were compound heterozygous for c.118C > T [p.R40X] and c.2647-7G > A [p.N882fs] on GAA, whereas, two patients showing a mild phenotype were compound heterozygous c.2647-7G > A [p.N882fs] and c.2276G > C [p.G759A] mutations. Quantitative expression analysis showed, in the patients carrying p.R40X/ p.N882fs, a significant (p 0.01) correlation between the levels of expression of the mutated allele and the age at onset of the disease. CONCLUSIONS: As far as we know, this is the largest informative family with late-onset Pompe disease described in the literature showing a peculiar complex set of mutations of GAA gene that may partially elucidate the clinical heterogeneity of this family.