scholarly journals Children who have cytolysis syndrome in debut of genetic diseases: analysis of primary morbidity

2021 ◽  
Vol 1 (4) ◽  
pp. 18-24
Author(s):  
Rima A. Ushakova ◽  
Svetlana P. Bochkareva ◽  
Anna A. Vereshhinskaja

Background. Cytolysis syndrome often helps to suspect liver pathology. However, a rare genetic disease may manifest under the guise of increased transaminases. No true etiology of the disease is then identified with the standard examination algorithm. It is not recognized for a long time. Patients diagnosed with unspecified hepatitis receive irrational treatment, which in turn leads to deterioration in the quality of medical care.Purpose. To analyze the medical history, laboratory test results and list of clinical symptoms in pediatric patients with genetic diseases in the debut, and to correlate an identified symptom complex with increased transaminases.Methods. The article presents the results of a retrospective study of 17 randomly selected cases of children with a first established diagnosis of Duchenne — Becker muscular dystrophy, glycogen storage disease, mucopolysaccharidosis followed up in 2010–2019. We used data from patient complaints, anamnesis vitae and anamnesis morbi, laboratory test results and list of clinical symptoms in the debut of genetic diseases. The statistical processing was performed by using parametric and nonparametric methods. Confirmation of the diagnosis was obtained by molecular genetic techniques and the test for expression of urine glycosaminoglycans. Confirming diagnostic technologies were used in the laboratory of molecular diagnostics and the laboratory of inherited metabolic diseases at the Bochkov Research Centre for Medical Genetics (Moscow).Results. A comparative analysis of medical history and clinical and laboratory data was performed in 9 patients with Duchenne — Becker muscular dystrophy, 5 patients with glycogen storage disease, and 3 children with mucopolysaccharidosis. Prolonged neonatal jaundice was observed in 22.2% of newborns with Duchenne muscular dystrophy. In myopathies, elevated transaminases originate from destroyed muscle fibers and are not associated with the breakdown of the liver cells. This fact is also confirmed by our discovery of a direct correlation between AST (r = 0.76) and ALT (r = 0.72) values with high activity of creatine phosphokinase (CPK), p < 0.05. Prolonged neonatal jaundice was observed in 40% of children with glycogen storage disease. Hepatomegaly was detected in all cases, due to which the volume of the abdomen increases giving a specific form to patients against the background of overweight, lag in physical development due to low growth in 80% of cases and a “puppet face” in 100% of children. There is strong correlation between the increased alkaline phosphatase and AST (r = 0.78), ALT (r = 0.81), p < 0.05. In the third group, there are three children with mucopolysaccharidosis. We did not find any significant increase in transaminases in this group of children.Conclusion. Against the background of progressive Duchenne — Becker muscular dystrophy, hyperenzymemia is detected in each male patient. There is correlation between elevated transaminases and high creatine phosphokinase. Cytolysis syndrome was found only in some cases of glycogen storage disease, and hyperenzymemia occurs against the background of typical clinical symptoms of the disease. In cases of mucopolysaccharidosis we have found no elevated transaminases, but there is hepatomegaly. In case of prolonged unexplained cytolysis syndrome, the pediatrician should conduct a diagnostic search to identify or exclude genetic diseases.

2020 ◽  
Vol 8 ◽  
Author(s):  
Shen Ying ◽  
Zhang Zhihua ◽  
Zheng Yucan ◽  
Jin Yu ◽  
Lin Qian ◽  
...  

Aim: The aim of this study was to investigate the clinical utility of panel-based next-generation sequencing (NGS) in the diagnostic approach of glycogen storage disease (GSD).Methods: We performed a retrospective review of the 32 cases with suspected GSDs between April 2013 and November 2019 through panel-based NGS, clinical and biochemical data and long-term complications.Results: Of the 32 clinical cases, we identified 41 different variants, including 24 missense (58.5%), one synonymous (2.4%), three nonsense (8%), one splice (2.4%), four frameshift (9.8%), one deletion (2.4%), four insertions (9.8%), two deletion-insertion (4.9%) and one duplication(2.4%), of which 13(31.7%) were previously unreported in the literature. In addition, patients with different types of GSDs showed important differences in biochemical parameters (i.e., CK, rGGT, TG, and UA).Conclusions: The panel-based NGS played an important diagnostic role in the suspicious GSDs patients, especially in the mild phenotype and ruled out detectable pathologic conditions. Besides, differences between our GSDs patients reflect biochemical heterogeneity.


2021 ◽  
Vol 9 ◽  
Author(s):  
Fengyu Wang ◽  
Fengli Wang ◽  
Xiaojun Zhou ◽  
Yingjie Yi ◽  
Jie Zhao

Glycogen storage disease (GSD) Ib is a rare genetic metabolic disorder caused by gene mutation in the glucose 6-phosphate transport gene SLC37A4 (OMIM# 602671). This study aimed to explore the association between a novel lipoprotein lipase (LPL) mutation and severe hypertriglyceridemia in a GSD Ib infant with severe hypertriglyceridemia. A 5-month-old girl was admitted to our hospital because of repeated episodes of low-grade fever over the past month and because of neutropenia. The patient was diagnosed with GSD Ib and severe hypertriglyceridemia based on clinical manifestations and laboratory test results. Next-generation sequencing and Sanger sequencing were then applied to DNA from the peripheral blood of the patient and her parents to analyze gene mutations. Pathogenicity prediction analysis was performed using Sorting Intolerant From Tolerant (SIFT) and PolyPhen-2 platforms. The results revealed that this infant carried a compound heterozygous variation in the SLC37A4 gene, a c.1043T &gt; C (p.L348P) mutation derived from her mother and a c.572C &gt; T (p.P191L) mutation derived from her father. In addition, a novel c.483delA (p. A162Pfs*10) frameshift mutation was found in the patient's LPL gene exon 4, which was derived from the heterozygous carrier of her father. The SIFT and PolyPhen-2 prediction programs indicated that these mutations were likely harmful. Medium-chain triglyceride milk and granulocyte colony-stimulating factor subcutaneous injection alleviated the symptoms. Our findings identified a novel LPL gene frameshift mutation combined with SLC37A4 gene compound heterozygous mutations in a GSD Ib infant with severe hypertriglyceridemia.


2016 ◽  
Vol 18 (10) ◽  
pp. 1037-1043 ◽  
Author(s):  
Ana I Vega ◽  
Celia Medrano ◽  
Rosa Navarrete ◽  
Lourdes R Desviat ◽  
Begoña Merinero ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document