Glicogenoses hepáticas no Brasil: inquérito nacional

Abstract

Objectives: To describe clinical and laboratory characteristics, treatment and outcomes of patients with hepatic glycogenosis followed at pediatric hepatology referral centers in Brazil. And to compare the findings with the type of hepatic glycogenosis. Methods: Multicenter and retrospective study of patients diagnosed with hepatic glycogenosis followed at 13 Brazilian centers. Data were collected from medical records. Quantitative variables were described as median, first and third quartiles. Categorical variables were described as absolute and relative frequencies. The Kruskal-Wallis test was used to compare quantitative variables by type of glycogenosis. Pearson's chi-square test and Fisher's exact test were used to compare categorical variables. The Wilcoxon test was used to compare measurements at two different moments (admission and last evaluation) of the variables of interest. Results were significant if the probability of significance was less than 5% (p < 0.05). Results: A total of 132 patients were included, 47.8% with type I hepatic glycogenosis, 9.8% with type III, 0.8% with type IV, 4.5% with type VI and 37.1% with type IX. Patients with type I glycogenosis manifested and were diagnosed earlier: medians of 4 (p<0.001) and 52.8 (p<0.034) months, respectively. They manifested with more episodes of hypoglycemia at clinical presentation (p<0.001), higher frequency of overweight and obesity (p=0.006), higher values of total cholesterol (p=0.04), triglycerides (p<0.001), venous lactate (p<0.001) and uric acid (p<0.001) upon admission. During follow-up, they presented, more frequently, microalbuminuria (p<0.001), other renal alterations (p<0.001) such as nephromegaly (57.7%), nephrolithiasis (34.6%) and arterial hypertension (30.8%), infections requiring hospitalization (p<0.001), hyperuricemia requiring allopurinol (p<0.001) and hepatic adenomas (p=0.003). The three liver transplant recipients were type I due to adenomas and/or frequent decompensations. They required treatment with raw starch earlier (p<0.001), a greater number of daily (p<0.001) and nocturnal (p<0.001) doses. There was a significant improvement in aminotransferases, lipids and lactate during follow-up. One patient type Ia died at 1.5 years of age due to sepsis. Patients with glycogen storage disease type III more frequently presented elevated values of alkaline phosphatase (p=0.003), alanine aminotransferase (p<0.001) and aspartate aminotransferase (p<0.001) upon admission. During follow-up, they presented more alterations in total creatine phosphokinase (p<0.001), higher incidence of skeletal myopathy (p=0.028) and cardiomyopathy (p<0.001). There was a significant improvement in alanine aminotransferase during the follow-up. Patients with type IX also presented, more frequently, alterations in aspartate aminotransferase (p<0.001) and alanine aminotransferase (p<0.001) upon admission. There was a lesser need for the use of raw starch (p<0.001), and significant improvement in length (p=0.007), body mass index (p=0.020) and aminotransferases during the follow-up. Evolution to cirrhosis occurred only in type IX patients (in 10.2%) at a median age of 3.5 years. Conclusion: It´s important to consider a high suspicion of type I hepatic glycogenosis in patients with history of hepatomegaly, persistent hypoglycemia, and laboratory alterations in lipids, lactate, and uric acid, aiming at early diagnosis and treatment. Monitor patients from a renal and infectious point of view, as well as for the formation of hepatic adenomas. Monitor patients with type III glycogenosis, paying attention to the development of myopathy and cardiomyopathy. Monitor patients with type IX, paying attention to liver function, due to the risk of progression to liver cirrhosis.