| Autor: |
Wilke MVMB; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos St., 2350, 3rd Floor, Porto Alegre 90035-903, Brazil.; Post Graduation Program Ciências da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil., de Oliveira BM; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos St., 2350, 3rd Floor, Porto Alegre 90035-903, Brazil.; Post Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil., Starosta RT; Division of Medical Genetics and Genomics, Washington University in Saint Louis, Saint Louis, MO 63130, USA., Shinawi M; Division of Medical Genetics and Genomics, Washington University in Saint Louis, Saint Louis, MO 63130, USA., Lu L; Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO 63130, USA., He M; Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO 63130, USA., Ma Y; Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO 63130, USA., Stoll J; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Washington University in Saint Louis, Saint Louis, MO 63130, USA., de Souza CFM; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos St., 2350, 3rd Floor, Porto Alegre 90035-903, Brazil.; Postgraduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil., de Siqueira ACM; Treatment Center of Inborn Errors of Metabolism, Instituto de Medicina Integral Professor Fernando Figueira, Recife 50070-902, Brazil., Vieira SMG; Pediatrics Gastroenterology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil., Cerski CT; Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil., Refosco LF; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos St., 2350, 3rd Floor, Porto Alegre 90035-903, Brazil., Schwartz IVD; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos St., 2350, 3rd Floor, Porto Alegre 90035-903, Brazil.; Post Graduation Program Ciências da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil.; Post Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil.; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil.; BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil. |
| Abstrakt: |
Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the GBE1 gene, which encodes the glycogen branching enzyme (GBE). GSD IV accounts for approximately 3% of all GSD. The phenotype of GSD IV ranges from neonatal death to mild adult-onset disease with variable hepatic, muscular, neurologic, dermatologic, and cardiac involvement. There is a paucity of literature and clinical and dietary management in GSD IV, and liver transplantation (LT) is described to correct the primary hepatic enzyme defect. Objectives: We herein describe five cases of patients with GSD IV with different ages of onset and outcomes as well as a novel GBE1 variant. Methods: This is a descriptive case series of patients receiving care for GSD IV at Reference Centers for Rare Diseases in Brazil and in the United States of America. Patients were selected based on confirmatory GBE1 genotypes performed after strong clinical suspicion. Results: Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly, failure to thrive, and elevated liver enzymes starting at the age of 5 months. Before LT at the age of two, empirical treatment with corn starch (CS) and high protein therapy was performed with subjective improvement in his overall disposition and liver size. Pt #2 is a 30-month-old Afro-American descent patient with the chief complaints of failure to gain adequate weight, hypotonia, and hepatosplenomegaly at the age of 15 months. Treatment with CS was initiated without overall improvement of the symptoms. Pt #3.1 is a female Latin patient, sister to pt #3.2, with onset of symptoms at the age of 3 months with bloody diarrhea, abdominal distention, and splenomegaly. There was no attempt of treatment with CS. Pt #4 is an 8-year-old male patient of European descent who had his initial evaluation at 12 months, which was remarkable for hepatosplenomegaly, elevated ALT and AST levels, and a moderate dilatation of the left ventricle with normal systolic function that improved after LT. Pt #1, #3.2 and #4 presented with high levels of chitotriosidase. Pt #2 was found to have the novel variant c.826G > C p.(Ala276Pro). Conclusions: GSD IV is a rare disease with different ages of presentation and different cardiac phenotypes, which is associated with high levels of chitotriosidase. Attempts of dietary intervention with CS did not show a clear improvement in our case series. |
