Genetic studies by NGS Panel
Panel for hereditary hemolytic anemia including membranopathies and enzymopathy (Code 10070)
This panel combines the panels with code 10061 + 10062.
Red blood cells have active anaerobic metabolism using glucose as an energy source. The major metabolic functions include maintaining membrane proteins, preserving iron hemoglobin in the Fe3 + state and modulating the affinity of hemoglobin for oxygen. These functions need the regulation of four components: ATP, NADH, NADPH, and 2,3 diphosphoglycerate. Enzymatic defects in these pathways produce hereditary hemolytic anemias due to red blood cell enzymopathies or glycogen storage disease. Common enzymatic defects include pyruvate kinase (PK) deficiency and glucose 6-phosphate dehydrogenase (G6PD) deficiency. Defects in other enzymes are less frequent and include hexokinase deficiency, glucose phosphate isomerase deficiency, diphosphoglycerate maltose deficiency, glutathione reductase deficiency, glutathione synthetase deficiency, glutathione peroxidase deficiency, gamma-glutamylcysteine synthetase deficiency, 5-nucleotidase pyrimidine deficiency, adenylate kinase 1 deficiency, phosphoglycerate kinase 1 deficiency, tri-phosphate isomerase deficiency 1, glycogen storage disease due to phosphofructo kinase deficiency, glycogen storage disease due to aldolase A deficiency, Overproduction of adenosine deaminase in erythrocytes and hereditary recessive methemoglobinemia type 1 and type 2.
G6PD deficiency causes hemolysis in response to oxidative stress such as drugs, dehydration and fever / infection, whereas PK deficiency is characterized by continuous hemolysis due to its activity in the main anaerobic glycolytic pathway.
Defects of the red blood cell membrane include hereditary spherocytosis and hereditary elliptocytosis, also called ovalocytosis. In these diseases there is a defect in the superficial membrane of the red blood cells that makes them have a sphere form in hereditary spherocytosis or an elliptical / oval shape in hereditary elliptocytosis. The red blood cells of these patients have a shorter life.
Hereditary spherocytosis is the most common cause of hemolytic anemia among people of Northern European descent. Less than 10% of patients with hereditary spherocytosis are manifested with the severe variant of hereditary pyropoyquilocytosis, which is characterized by severe, transfusion-dependent haemolytic anemia, which begins in childhood and can also manifest with neonatal jaundice.
Complications that can occur due to severe anemia include growth retardation, mandibular and frontal prominence, splenomegaly, and early disease of the gallbladder.
Gilbert syndrome is the most known alteration in bilirubin metabolism and is manifested by an increase in unconjugated bilirubin. It is due to a deficiency of the enzyme uridine diphosphate glucuronyl transferase (UGT) responsible for the conjugation process. In the literature, cases have been described in which Gilbert Syndrome and hereditary spherocytosis coexist, a situation that is accompanied by a higher degree of hyperbilirubinemia with formation of gallstones. Therefore, Gilbert’s Syndrome is a modifying factor of hereditary hemolytic anemias due to membranopathies.
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