Glucose 6 phosphate dehydrogenase deficiency . Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most frequent enzyme deficiency of the red blood cell in humans. It is believed that 200 million people are affected, and the reason for this is that their deficit confers resistance to malaria. It is precisely when studying hemolytic anemia caused by primaquine, an antimalarial drug, that this deficit is discovered.
Summary
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- 1 Detail
- 2 Clinical forms
- 3 Genetics
- 4 Classification
- 5 Laboratory
- 6 Hematological
- 7 Biochemicals
- 8 Treatment
- 9 Source
Detail
G6PD is a very old enzyme in evolution, as it is found in all organisms from yeast and protozoa to plants and animals. In mammals it is cytoplasmic and is found in all cells of the body. The role of G6PD in the red blood cell is a metabolic role due to its reductive potential and thus, the deficiency of this enzyme causes oxidative damage in it and its subsequent destruction. The half-life of this enzyme is 60 days and reflects step by step the age of the red blood cell since it is unable to form new protein molecules and thus, the reticulocyte, which is the youngest red blood cell, has 5 times more enzymatic activity than senescents.
Clinical forms
The deficiency of this enzyme manifests itself in the individual in 3 clinical forms: (a) acute hemolytic anemia (AHA), (b) chronic non-spherocytic hemolytic anemia (AHCNE), and (c) neonatal hemolytic anemia. This latter presentation is currently believed to be due more to liver immaturity due to enzyme deficiency in the liver cell than to hemolysis itself, since newborns do not develop anemia when they become jaundiced.
In AHAs, individuals do not have anemia or hemolysis normally, this is evident only under stress, such as drug administration, infections or ingestion of fava beans (favism) and is presented by people with the most frequent mutations, such as African (A-) and the Mediterranean. The following drugs that should not be indicated for G6PD deficient patients: Antimalarials ( Primaquine , Pamaquine ), Sulfonamides ( Sulfanilamide , Sulfapiridine , Sulfadimidine , Sulfa + Trimethorpin , Sulfamethoxazole ), Nitrofurantoin ( Nitrofurantoin ,Furazolidone , nitrofurazone ), Other ( Nalidixic Acid , Chloramphenicol , Probenecid , Methylene Blue , Blue Toloudina , Naphthalene , Trinitrotoluene , phenylhydrazine , Phenazopyridine ) and Anthelmintics ( B-Naphthol , Niridazole ).
AHCNE are produced by rare variants where the mutation is located in the NADPH binding region and is not so dependent on the activity of the enzyme, which is sometimes quite high (35%). In general, hemolysis is minor, although anemias as intense as thalassemia major have been described. The red blood cell , in these cases, is not able to resist even the stress of circulation and is in permanent destruction.
Genetics
The G6PD gene was cloned in 1984. It is located in the telomeric region of the long arm of the X chromosome. This gene is 20 kb long and has 13 exons. The coding sequence begins in exon 2 since exon 1 does not code. The normal enzyme is called G6PD B and it is an oligomer with a single polypeptide chain of 515 amino acids. G6PD deficiency may be due to deletions or point mutations affecting transcription, processing, or the primary structure itself. Although the enzyme activity is very low (1%) it is never totally absent.
Amino acid substitutions alter the function of the enzyme either by decreasing its stability, affecting the catalytic function of G6PD. The electrophoretic study and the kinetic properties of the residual enzyme have shown that not all ethnic groups have the same mutation and thus more than 400 mutations have been described.
With the current possibility of using the polymerase chain reaction for the study of individual exons or groups of exons, the analysis of G6PD mutations has been simplified and currently around 100 variants have been described.
Classification
G6PD deficiencies have been categorized by the World Health Organization (WHO) according to enzyme activity into 5 classes. Of the 100 different G6PD mutations described to date, they have been identified in all exons except for exon 1 that has no coding sequence and in the vast majority of cases there is only one amino acid substitution. 25% of the mutations are in exon 10 that extends from nucleotide 1052 to 1287, and of these, all but 2 that are at the 5 ‘end of the exon, are class I. The sequence has been thought of The amino acid encoding this exon is found at the NADP binding site because some of these variants are activated with high concentrations of NADPH.
Laboratory
To diagnose that there is a PK deficiency, there are different laboratory tests, both routine and specific.
Hematologic
Hemoglobin between 3 to 4 g / dl, eccentrocytes (they have a displacement of hemoglobin towards one end), Heinz bodies (denatured hemoglobin that precipitates inside the erythrocyte).
Biochemical
An increase in hemoglobin , plasma bilirubin , and urinary and fecal urobinogen , a decrease in haptoglobinemia , hemoglobinuria, and hemosidenuria are observed .
The definitive diagnosis is made in techniques such as: quantitative enzymatic test, which is the measure of the enzymatic activity in the hemolysate in IU per gram of hemoglobin (normal range: 4.6 – 13.5 IU / gHb), fluorescence test, methemoglobin reduction test, ascorbate-cyanide test and electrophoresis.
Treatment
G6PD deficiency lacks etiological treatment and must always be palliative, based on blood transfusions when required; Furthermore, once the diagnosis is established, care should be taken to avoid the patient’s contact with all those substances capable of triggering the hemolytic condition.
