Pompe disease in a five-year child

Aim. To demonstrate a clinical case of orphan hereditary disease from the group of lysosomal storage diseases - Pompe disease (glycogenosis type II) in a five-year child. Materials and methods. Anamnestic data, clinical and laboratory parameters and treatment of a five-year child with Pompe disease. The patient was observed in the gastroenterological department of the Children’s Regional Clinical Hospital. Results. Child admitted with complaints of muscle weakness, difficulty climbing stairs, rare headaches. According to his history, his mother turned to the pediatrician about the prolonged course of a respiratory infection. An outpatient examination revealed a significant increase in the levels of alanine aminotransferase and aspartate aminotransferase. Viral hepatitis was excluded. The child was hospitalized in a hospital for further examination with hepatitis, unspecified etiology (non-infectious). Examination of the child revealed a lag in physical development, muscle hypotension, hepatomegaly, liver dysfunction, and increased total creatine phosphocanase and IgE. A decrease in the activity of acid α-1,4-glucosidase in the spot of dried blood was determined according to tandem mass spectrometry and gene mutations GAA DNA diagnostic method. Diagnosed with Pompe disease (glycogenosis type II). Myopathic syndrome. The treatment with the genetic engineering enzyme-substituting drug Mayozayme was started at a dose of 20 mg/kg, intravenously, once every two weeks. Conclusion. Pompe disease is a rare pathology characterized by a low frequency of prevalence and polymorphism of clinical manifestations, complicating the diagnosis. Timely diagnosis of the disease and the earliest possible appointment of pathogenetic therapy are required to improve patients’ quality of life, slow down the progression of the disease, and prevent the development of life-threatening complications.

Exercise, nutrition and enzyme replacement therapy are efficacious in adult Pompe patients: report from EPOC Consortium

Pompe Disease, also known as glycogenosis type 2, is due to deficiency in lysosomal alpha- glucosidase, a lysosomal hydrolase, which presents infantile and late onset subtypes (LOPD). The myopathy in LOPD can be reversed by Enzyme Replacement Therapy (ERT), but might benefit from a concomitant low carbohydrate - high protein diet and aerobic exercise treatment. From 65 Late onset Pompe cases, we were able to obtain in 58 a self-reported evaluation, most of them gave a positive efficacy evaluation of Enzyme Replacement Therapy and they were classified by a self-administered scale as Responders or non-Responders. A cooperative study of a clinical group on LOPD monitored age, sex, BMI, Gardner-Medwin-Walton scale and six minute walking test (6MWT). The only clinical parameters that were significantly associated with a Responder category were the pre-ERT walking distance (p<0.035) and the use of regular diet, exercise or both (p<0.029). The present study shows that in LOPD this condition can be treated by ERT, but also benefits from concomitant diet and aerobic exercise therapy.

ANTHROPOMETRIC AND DIETARY ASSESSMENT OF PATIENTS WITH GLYCOGENOSIS TYPE I

ABSTRACT Objective: To perform anthropometric and dietary evaluation of patients with glycogenosis type Ia and Ib. Methods: This cross-sectional study is composed of a sample of 11 patients with glycogenosis divided into two subgroups according to the classification of glycogenosis (type Ia=5 and type Ib=6), aged between 4 and 20 years. The analyzed anthropometric variables were weight, height, body mass index, and measures of lean and fat body mass, which were compared with reference values. For dietary assessment, a food frequency questionnaire was used to calculate energy and macronutrients intake as well as the amount of raw cornstarch consumed. Mann-Whitney U test and Fisher’s exact test were performed, considering a significance level of 5%. Results: Patients ingested raw cornstarch in the amount of 0.49 to 1.34 g/kg/dose at a frequency of six times a day, which is lower than recommended (1.75-2.50 g/kg/dose, four times a day). The amount of energy intake was, on average, 50% higher than energy requirements; however, carbohydrate intake was below the adequacy percentage in 5/11 patients. Short stature was found in 4/10 patients; obesity, in 3/11; and muscle mass deficit, in 7/11. There were no statistical differences between the subgroups. Conclusions: In patients with glycogenosis type I, there was deficit in growth and muscle mass, but no differences were found between the subgroups (Ia and Ib). Although the diet did not exceed the adequacy of carbohydrates, about 1/3 of the patients presented obesity, probably due to higher energy intake.

Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene

BackgroundPHKG2-related liver phosphorylase kinase deficiency is inherited in autosomal recessive pattern and is a rare type of liver glycogenosis. We demonstrated the clinical presentation and genetic determinants involved in children with PHKG2- related liver phosphorylase kinase deficiency.MethodologyTen Pakistani children with liver phosphorylase kinase from seven different families, were enrolled over a period of 18 months. All regions of the PHKG2 gene spanning exons and splicing sites were evaluated through targeted exome sequencing. Variants were analyzed using different bioinformatics tools. Novel variants were reconfirmed by direct sequencing.ResultsSeven different variants were identified in PHKG2 gene including five novel variants: three stop codons (c.226C>T [p.R76*], c.454C>T [p.R152*] and c.958C>T [p.R320*]), one missense variant c.107C>T (p.S36F) and one splice site variant (c.557-3C>G). All five novel variants were predicted to be damaging by in Silico analysis. The variants are being transmitted through recessive pattern of inheritance except one family (two siblings) has compound heterozygotes. Laboratory data revealed elevated transaminases and triglycerides, normal creatinine phosphokinase and uric acid levels but with glycogen loaded hepatocytes on liver histology.ConclusionPHKG2 related liver phosphorylase kinase deficiency can mimic both liver glycogenosis type I (glucose-6-phosphatase deficiency) & III(amylo-1,6 glucosidase) and characterized by early childhood onset of hepatomegaly, growth restriction, elevated liver enzymes and triglycerides. Molecular analysis would be helpful in accurate diagnosis and proper treatment. The symptoms and biochemical abnormalities in liver glycogenosis due phosphorylase kinase deficiency tend to improve with proper dietary restrictions but need to be monitored for long-term complications such as liver fibrosis and cirrhosis.