Glucose-6-phosphate dehydrogenase deficiency

from Wikipedia, the free encyclopedia
ICD-10 codes G6PD deficiency
(glucose-6-phosphate dehydrogenase deficiency)
D55.0 Glucose-6-phosphate
dehydrogenase (G6PD) deficiency
with anemia
E74.8 Glucose-6-phosphate
dehydrogenase (G6PD) deficiency
without anemia
Information in medical databases
OMIM Record +305900
HGMD Data set G6PD

The glucose-6-phosphate dehydrogenase deficiency (short: G6PD (H) deficiency ; synonyms: favism , favabean disease ) is an inherited deficiency of the enzyme glucose-6-phosphate dehydrogenase in humans due to a mutation of the G6PD gene the X chromosome , section q28 (Xq28). The deficiency of the enzyme G6PD leads to an increase in the ability of the red blood cells ( erythrocytes ) to be destroyed by external factors in the form of hemolysis by changing the sugar metabolism . The symptoms of G6PD deficiency are highly variable depending on the mutation (allelic variant) and gender of the person affected: they range from freedom from symptoms to a life-threatening hemolytic crisis. Three typical forms are symptom-free, induced hemolytic anemia (hemolytic crisis) and chronic hemolytic anemia with hemolytic crises. Newborns with a G6PD deficiency can suffer from prolonged or particularly severe neonatal jaundice (icterus neonatorum). The severe forms almost exclusively affect boys and men.

Summarizing all variants and characteristics, around 1.18 billion people in the world have some form of G6PD deficiency. G6PD deficiency is mainly found in geographical regions where malaria was or is widespread. The G6PD deficiency also occurs in malaria-free areas, but is much less common. This distribution of the G6PD deficiency represents a balanced polymorphism : the relative resistance of the affected women to malaria infections outweighs the disadvantage of the sensitivity of the affected men from an evolutionary point of view. The disease was observed for the first time in connection with the consumption of broad beans (fava bean, field bean , broad bean), to which the alternative name favism can be traced back. In addition to the fava beans, substances such as henna or various drugs have the property of triggering hemolytic crises. In connection with the COVID-19 pandemic, various medical publications explicitly pointed to complications with the drug hydroxychloroquine . This could lead to hemolysis and microembolisms and thus death.

The treatment of the G6PD deficiency depends on the form and the person affected. Knowledge of the G6PD deficiency is crucial for all those affected, as this means that factors that trigger a hemolytic crisis such as fava beans or certain medications can be avoided. In a hemolytic crisis, avoiding or removing the trigger immediately is critical; Blood transfusions may be required in rare cases. The prognosis of the G6PD deficiency depends on the type of G6PD deficiency: it is good overall, very good if those affected are informed and the mild form of the G6PD deficiency is present, and is not associated with a reduced life expectancy . People with severe G6PD deficiency and frequent hemolytic crises have a higher morbidity ( susceptibility to disease) than people without G6PD deficiency.

root cause

Normal function of glucose-6-phosphate dehydrogenase (G6PD)

Glucose-6-phosphate dehydrogenase

The glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is an enzyme with a molar mass of not more than 59,289  Dalton (Da), the 249-515 amino acids comprises in the space and a homodimer or a homotetramer forms. It belongs to the enzyme family of oxidoreductases and forms its own subfamily of glucose-6-phosphate dehydrogenases. G6PD exists in two isoforms , one short and one long. The long isoform (515 amino acids) is found in lymphoblasts , granulocytes and sperm cells . The short isoform (249 amino acids) is found in the liver and above all in the red blood cells ( erythrocytes ). Both isoforms bind NADP twice: once at the N-terminal end of the enzyme as a cofactor (between amino acids 27 and 210) and once as a structural element at the C-terminal end.

The enzyme G6PD catalyzes the conversion of glucose-6-phosphate into D-glucono-1,5-lactone-6-phosphate (6-phosphoglucono-δ-lactone) with the reduction of NADP + to NADPH . NADPH is a cofactor for the enzyme glutathione reductase . Its substrate glutathione is in its oxidized form as a dimer with a sulfide bridge (GSSG). Glutathione reductase dissolves the sulphide bridge of the dimer by reduction, so that two monomers reduced glutathione (GSH) are formed; here NADPH is oxidized to NADP + . Glutathione is a tripeptide that occurs in almost all human cells, which reduces oxidants that react as radicals , and is therefore referred to as a radical scavenger or an antioxidant . Examples of aggressive oxidants occurring in the metabolism are oxygen radicals , hydroxyl radicals and hydrogen peroxide . Certain drugs or their metabolic intermediates also react radically (z. B. primaquine , nitrofurantoin or sulfanilamide ), as are the alkaloids Vicin and Convicin the broad bean . The antioxidant function of glutathione requires that the substance is present in a reduced state.

The NADP + produced when glutathione is reduced by glutathione reductase is in turn "recycled" by the G6PD to NADPH. In terms of balance, G6PD therefore helps to maintain the antioxidant capacity of the human body.

Pathomechanism (pathophysiology)

If the enzyme glucose-6-phosphate dehydrogenase (G6PD) is reduced in its activity or produced less than normal due to changes in the G6PD gene, these changes cause a reduction in the conversion of NADP to NADPH (as well as of glucose-6-phosphate in 6-phosphoglucono-δ-lactone as a starting point for further steps of the pentose phosphate path , see below). The reduced conversion of NADP into NADPH has consequences in the glutathione metabolism. The enzyme glutathione reductase, which is responsible for the conversion of oxidized glutathione (without antioxidant effect) into reduced glutathione (with antioxidant effect) with the simultaneous conversion of NADPH into NADP, can no longer catalyze this reaction as usual due to the lack of NADPH. As a result of this reduced reduction of oxidized glutathione, the amount of reduced glutathione and thus the antioxidant capacity of the human body decreases. If substances with an oxidative effect (oxidants) now appear in the body, if the amount of reduced glutathione has dropped sharply, its antioxidant protective effect cannot be maintained: The oxidants damage the cell components, especially the cell membrane, but also proteins, ultimately irreversible Damage to the affected cells and subsequently to their demise.

In contrast to other cells in the human body, erythrocytes get their energy almost exclusively from glucose. 90–95% of the glucose is used via glycolysis to produce ATP and thus energy. The remaining 5-10% glucose is used for the formation of NADPH by G6PD and another enzyme of the pentose phosphate pathway (6-phosphogluconate dehydrogenase). Erythrocytes do not have G6PD-independent mechanisms for NADPH production to a significant extent. If the activity of G6PD is reduced, the amount of NADPH falls, followed by the amount of reduced glutathione. The erythrocyte therefore no longer has adequate antioxidant protective mechanisms. In people with G6PD deficiency, the action of oxidants damages and destroys the erythrocytes ( hemolysis ). If it is done quickly, the process corresponds to a hemolytic crisis. A deficiency in erythrocytes that arises in this way is called hemolytic anemia . If the process is slow, hemolytic anemia of milder severity develops.

Since erythrocytes specialize in oxygen transport by binding to hemoglobin , they generate a particularly large amount of oxygen radicals. Therefore, erythrocytes are always affected to a certain extent with a G6PD deficiency. Depending on the gene mutation and subsequent change in the G6PD enzyme, the extent of hemolysis and the shortening of the lifespan of the erythrocytes vary. As a compensation, the formation of red blood cells ( erythropoiesis ) is increased, whereby there are limits to the compensation.

All known malaria pathogens (e.g. Plasmodium falciparum ) go through a life phase in erythrocytes. The shorter lifespan of the erythrocytes with G6PD deficiency therefore reduces the chance of the pathogen multiplying and reproducing. This connection is held responsible for the relative protective effect of a G6PD deficiency against malaria.

Inheritance

Figure 3. Position of the G6PD gene on the human X chromosome
Fig. 4. Inheritance (biology) of the G6PD deficiency (genetic transmission with all combinations)

The glucose-6-phosphate dehydrogenase gene (G6PD gene) is located on section q28 of the X chromosome (Xq28) in humans (DEHUG6 locus ; see Figure 3). Therefore, the G6PD gene is inherited with the X chromosome (X chromosomal; see Figure 4).

If an altered or pathological G6PD gene on an X chromosome is passed on to the offspring (children), the sex of the subsequent affected person is of particular importance due to the X-linked inheritance. In the case of a female offspring who has passed on a mutated G6PD gene, a healthy G6PD gene is available on the second X chromosome ( heterozygosity ). According to the X inactivation ( Lyon hypothesis ), G6PD genes together with the X chromosome are activated or deactivated at random and in a disordered manner. The deactivated X chromosome with the deactivated G6PD gene cannot function as the basis for protein production. Correspondingly, no defective G6PD enzymes are produced using inactive defective G6PD genes. Intact inactive G6PD genes are also not used for the synthesis of G6PD enzyme. In the female individuals affected in this way, two groups of erythrocytes result - one with a modified G6PD gene and one with a normal G6PD gene. Depending on the distribution of the two groups, which can turn out very differently depending on the random X-inactivation, the affected girls and women have a highly variable and mostly weak characteristic expression of the G6PD deficiency and thus - also very variable - few or no symptoms.

In male descendants who inherit an X chromosome with defects in the G6PD gene, the second X chromosome is missing (male individuals, in contrast to females, have one X and one Y chromosome). They are hemizygous for the disease . This also means that X inactivation does not occur, so that the genetic information of the single X chromosome is always translated into proteins. If a defective G6PD gene is present, a correspondingly defective G6PD enzyme is therefore always produced. Since the Y chromosome does not contain any information about G6PD, only one group of erythrocytes with a defective G6PD enzyme is ever formed in male offspring. As a result, affected boys and men usually have significantly more severe symptoms than affected girls or women, as they do not have a group of red blood cells with normal G6PD activity. The probability of developing a serious G6PD deficiency is therefore much higher for boys and men than for girls or women.

Girls or women are only more seriously ill with G6PD deficiency if both X chromosomes each have a defective G6PD gene ( homozygous ). This presupposes that both the father and the mother of such female offspring have a mutation in the G6PD gene. But this is rarely the case.

Variants of the G6PD gene

The enzyme G6PD has two variants: A and B. These variants are caused by genetic changes at the DNA level. In contrast to the mutations, the resulting proteins have no pathological function. The A variant is defined by exchanging a DNA building block (nucleotide) at position 376 of the DNA of the G6PD gene (nucleotide substitution). For the nucleotide adenine is guanine used. This swap causes a change in the amino acid encoded by this DNA segment. Instead of aspartic acid, asparagine is encoded so that the resulting G6PD protein is modified accordingly. The B variant does not have this change in the DNA building block sequence (DNA base sequence) at position 376. There is no significant difference in the function and functionality of the two variants of the G6PD enzyme without further changes (mutations) being present.

The variants of the G6PD enzyme have a specific geographical distribution. The A variant is found mainly in people from Africa (all regions below the Sahara) and in people of African origin, such as the African-American population group in the USA. The A variant is also very common in China. The B variant is typical for the Mediterranean region. It occurs both in southern European population groups as well as in Middle Eastern and North African population groups.

In the case of a mutation of the G6PD gene, people with the A variant of G6PD - expressed as a rough rule - show less severe symptoms than people with the B variant. However, it is quite possible and it happens that people with a pathological A variant of G6PD have more severe symptoms than people with a pathological B variant.

Mutations in the G6PD gene

The G6PD gene is approximately 18,000 base pairs (bp) in size and has 13 exons . The exons code for the protein glucose-6-phosphate dehydrogenase comprising 249-515 amino acids (depending on the isoform ). A total of 149 mutations of the G6PD gene are currently (23 September 2006) known, identified by molecular genetics and described in the specialist literature. 139 of these are missense or nonsense mutations , 8 small deletions , 1 large deletion and 1 mutation of splicing .

The following variants and mutations of the G6PD gene are known and described in molecular genetic terms:

Table 1. Described mutations and variants of the G6PD range
Variant or mutation G6PD gene protein
designation Short name
G6PD protein isoform		 OMIM code Type Subtype position position Structural change Function change
G6PD-A (+) Gd-A (+) G6PD A +305900.0001 Polymorphism nucleotide A → G 376
(exon 5) 		126 Asparagine → aspartic acid (ASN126ASP) No enzyme defect (variant)
G6PD-A (-) Gd-A (-) G6PD A +305900.0002 Substitution nucleotide G → A 376
(exon 5)
and
202 		68
and
126 		Valine → methionine (VAL68MET)
asparagine → aspartic acid (ASN126ASP)
G6PD-Mediterranean Gd-Med G6PD B +305900.0006 Substitution nucleotide C → T 563
(exon 6) 		188 Serine → Phenylalanine (SER188PHE) Class II
G6PD-Canton Gd-Canton G6PD A +305900.0021 Substitution nucleotide G → T 1376 459 Arginine → leucine (ARG459LEU) Class II
G6PD-Chatham Gd-Chatham G6PD +305900.0003 Substitution nucleotide G → A 1003 335 Alanine → threonine (ALA335THR) Class II
G6PD-Cosenza Gd-Cosenza G6PD B +305900.0059 Substitution nucleotide G → A 1376 459 Arginine → proline (ARG459PRO) G6PD activity <10%, thus a high proportion of sick people.
G6PD-Mahidol Gd-mahidol G6PD +305900.0005 Substitution nucleotide G → A 487
(exon 6) 		163 Glycine → Serine (GLY163SER) Class II
G6PD-Orissa Gd-Orissa G6PD +305900.0047 Substitution nucleotide 44 Alanine → glycine (ALA44GLY) NADP binding site affected. Greater stability than other variants.
G6PD-Asahi Gd-Asahi G6PD A- +305900.0054 Substitution nucleotide (several) A → G
±
G → A 		376
(exon 5)
202 		126
68 		Asparagine → aspartic acid (ASN126ASP)
valine → methionine (VAL68MET) 		Class III.

Epidemiology (occurrence)

Approx. G6PD deficiency affects 200 million people in some form worldwide. People from current or former malaria areas are significantly more often affected by the G6PD deficiency in all forms than people who do not come from such regions. Corresponding to the area in which malaria spreads (both present and past), there are increased incidences of G6PD deficiency in the tropics and subtropics . The following regions are characterized by an increased incidence of G6PD deficiency:

Table 2. Prevalence and incidence of G6PD deficiency by geographic region of the world - selection
North America The population groups with Afro-American or Mediterranean-European as well as Middle Eastern and Far Eastern descent are affected here
United States In the Afro-American population, 12.8% of all newborns in this group have a G6PD deficiency.
Central America All population groups affected
Mexico Prevalence of all G6PD forms 0.71%.
South America All population groups affected
Brazil In the state of Rio Grande do Sul , newborns (n ​​= 2799): 1.4% complete G6PD deficiency, 6.4% partial G6PD deficiency, total 7.9%.
middle East All population groups affected.
Abu Dhabi Newborn screening in 8,198 newborns: 9.1% (746) newborns are affected by G6PD deficiency.
Bahrain Prevalence 25% in newborn screening 1985.
Iraq
Iran In the Iranian provinces of Mazandaran and Guilan on the Caspian Sea , the prevalence of G6PD deficiency is 8.6–16.4%. The following variants of G6PD were found: G6PD-Mediterranean 66.2%, G6PD-Chatham 27% and G6PD-Cosenza in 6.75% of those affected.
Israel 806 male and female newborns were examined: 30.2% of all boys and 10.4% of all girls had a severe G6PD deficiency. 14% of the affected girls had a father who came from a population with a low prevalence for G6PD deficiency.
Jordan Newborn screening in 181 newborns. 11% of all female and 12% of all male newborns have some form of G6PD deficiency.
Lebanon Affected men 10: 1,000, affected women 0.4: 1,000. For men over 14 years of age, 36 affected persons in 3,000 examined persons (1.2% or cumulative incidence 12: 1,000).
Cyprus 6.4% of adult men have a G6PD deficiency: of these, 52.6% have the Mediterranean mutation 563C-> T in exon 6 (Ser188Phe) of the G6PD gene.
Southern Europe All population groups affected.
Greece 1,286,000 newborns (male and female) were examined between 1977 and 1989. A G6PD deficiency occurred in 3.14% of all examined (corresponds to 40,349 affected persons); 1 out of 22 male and 1 out of 54 female subjects were affected.
Italy In the newborn screening incidence by measurements 0.9: 1,000, calculated according to Hardy-Weinberg's law 4.8: 1,000.
In the province of Cosenza , G6PD deficiency was found in 209 of 16,787 boys (1.24%). 99 of the 209 affected boys had a severe G6PD deficiency (0.59%).
Portugal 0.51% of 15,208 men are G6PD deficient.
Spain Newborn screening for G6PD deficiency in Catalonia : of 3,189 newborns examined (including newborns with a migrant background), 29 showed some form of G6PD deficiency (0.91%), with 3 of 29 recorded cases being found in newborns of Spanish origin .
In Menorca, the prevalence is 9.7 / 1,000 for men (11 affected out of 1139 examined, corresponding to 0.97%).
North africa All population groups affected.
Libya The prevalence of G6PD deficiency in eastern Libya is 2.8% for men and 1.8% for women.
Tunisia In 325 subjects, the incidence of G6PD deficiency was 1.84%. Of those affected, 96.2% had Mediterranean type B (+), 1.96% had African type A (+).
Asia - Middle East and Far East All population groups affected.
Afghanistan In a study of Afghan refugees in Pakistan, 15.8% of the Pathan population and 7.0–9.1% of Uzbeks showed some form of G6PD deficiency. 2.9% of the Tajiks and 2.1% of the Turkmens were also affected.
China In China as a whole, 6,683 out of 155,879 volunteer test subjects (4.29%) had some form of G6PD deficiency.
India In the province of Rajasthan , 55 of 1,198 children (4.59%) were found to have some form of G6PD deficiency.
Indonesia In North Sumatra , 6.0% of all boys in Nias Province, 3.9% of all boys in Asahan Province and 0.9% of all boys in Medan City were found to have some form of G6PD deficiency.
Japan 9,620 children of atomic bomb survivors were screened in Hiroshima and Nagasaki . 0.11% of the male and 0.42% of the female children in Hiroshima and 0.16% of the male and 0.31% of the female children in Nagasaki had some form of G6PD deficiency. A total of 10 variants or changes in the G6PD enzyme were identified, with 3 new variants each being described in Hiroshima and Nagasaki.
Malaysia Newborn screening in 8,975 newborns between 1985 and 1986 showed an incidence of 4.5% in the Chinese population, 3.5% in the Malaysian, and 1.5% in the Indian population.
Myanmar (Burma) In the state (region) of Shan with malaria endemic 66 of 311 examined with G6PD deficiency corresponding to 21.2% (variant G6PD-Mahdiol).
Pakistan All forms of G6PD deficiency occur in 1.8% of the male population (1.07% in Kashmiris , 1.47% in Punjab residents , 2.77% in Sindhis and 3.17% in Pathans).
Singapore Newborn screening of approximately 1,600,000 newborns with an incidence of 1.62% in all newborns (3.15% in males, 0.11% in females).
Tajikistan Prevalence 2.1% (all forms of G6PD deficiency)
Thailand Prevalence in males 3 to 18% depending on the geographical region: the most common G6PD mutation is G6PD-mahidol (163Gly → Ser).
The prevalence in 505 male newborns examined is 12.08%.
61 out of 505 male newborns had some form of G6PD deficiency.
Vietnam Prevalence in the Kinh 0.5% and Mong 0.7% population: both groups do not live in malaria-endemic areas. In the population living in malaria endemic areas of Vietnam, the prevalence is 9.7 to 31%.
Africa (Sub-Sahara) All population groups affected
Kenya Prevalence in the lowlands of the malaria endemic area 7%, in the highlands of the malaria endemic area 1%.
South Africa In the population group of Greek descent in Cape Town , 6.7% of all male subjects examined had a form of G6PD deficiency.
Northern and Central Europe Population groups with a migration background from subtropical and tropical regions affected (including the Mediterranean region)
France In newborn screening, 6% boys affected by G6PD deficiency and 1% girls affected.
Netherlands 668 pregnant women and 754 healthy newborns from ethnic minorities in the Netherlands were screened for G6PD deficiency. The prevalence across all groups combined was 6.6% in men and 5.2% in women. The highest incidence of G6PD deficiency was found among Africans of sub-Saharan origin (black Africans).

Symptoms and clinical forms

Icteric sclera in a four-year-old with proven genetic G6DH deficiency and manifest haemolytic anemia after consumption of fava beans .

The glucose-6-phosphate dehydrogenase deficiency is very different due to its different forms and manifestations. In addition to the genetic change in the G6PD gene and gender, the possible presence of other congenital or acquired blood diseases (example: iron deficiency anemia) and exposure of the person affected to substances that can trigger hemolysis are important for the presence of symptoms or the clinical form .

For triggering substances, see also : Favism

Freedom from complaints

Most girls and women with a G6PD deficiency are symptom-free in childhood and adulthood. In these patients or affected persons, a reduction in activity can be determined by measuring the activity of the G6PD in the erythrocytes; Hemolysis with subsequent clinical symptoms such as jaundice (jaundice), anemia, feeling weak (malaise) or circulatory failure (in severe cases of hemolysis) does not occur. Even if substances that can trigger hemolysis are ingested or supplied, hemolysis practically never occurs, since the residual activity of G6PD is almost always sufficient to prevent damage (hemolysis) of the erythrocytes.

Only in newborns, if there is a glucose-6-phosphate dehydrogenase deficiency, prolonged or increased neonatal jaundice (icterus neonatorum) can occur, which does not necessarily lead to illness or damage to the affected newborn. On the basis of symptoms alone, prolonged or increased neonatal jaundice caused by G6PD deficiency cannot be differentiated from neonatal jaundice of any other cause.

diagnosis

The diagnosis of G6DH deficiency is suspected if patients of certain ethnic groups (see epidemiology) develop one or more of the following symptoms (especially if there is a 'positive family history', i.e. if the disease is known to blood relatives):

  • Anemia,
  • Jaundice or others
  • Hemolysis symptoms

Laboratory parameters:

  • Blood count and reticulocyte count; in acute G6PD deficiency, Heinz bodies could be seen in the blood smear;
  • Liver enzymes (to rule out other causes of jaundice);
  • Lactate dehydrogenase (increased with hemolysis and a marker of hemolytic severity)
  • Haptoglobin (decreased with hemolysis as the free haptoglobin is measured);
  • "Immediate antiglobulin test" (direct Coombs test ) - in the case of G6DH deficiency it should be negative, otherwise this indicates immunologically induced hemolysis.

If there are enough reasons to suspect a G6PD deficiency, the "Beutler test" (fluorescent spot test) can serve to confirm the diagnosis. The Beutler test is a quick and inexpensive test that shows NADPH produced by G6PDH under UV light. If the blood cells don't fluoresce, the test is positive. The test may be false negative in patients undergoing acute hemolysis for unknown causes. It is therefore only meaningful 2–3 weeks after such a hemolytic episode.

classification

According to the WHO, G6PD deficiency can be divided into different classes according to the measured functionality ( enzyme activity ) of G6PD.

Table 3. Classification of G6PD deficiency according to enzyme activity - WHO classification
Class WHO Enzyme activity in erythrocytes in% normal Clinical picture
class 1 reduced chronic hemolytic anemia
2nd grade <10% severe G6PD deficiency
Class 3 10-60% moderate G6PD deficiency
Grade 4 normal activity (60% -100%) no G6PD deficiency
Class 5 increased activity (> 110%) no G6PD deficiency

Differential diagnosis

Due to its variable symptoms and characteristics, the G6PD deficiency can sometimes be very difficult to differentiate from other diseases.

Jaundice (jaundice)

A distinction needs to be made between jaundice ( jaundice ) caused by G6PD deficiency and other forms of jaundice caused by other circumstances and triggers:

Newborn jaundice (jaundice neonatorum)
In classic neonatal jaundice , the symptoms and signs of hemolysis that are found in G6PD deficiency are usually absent.
Haemolytic jaundice of the newborn (Morbus haemolyticus neonatorum)
The distinction between this jaundice and that of G6PD deficiency can be very difficult. The hemolytic disease of the newborn is a positive Coombs' test proved which provides evidence for hemolysis-causing antibodies. A negative Coombs test suggests a G6PD deficiency; The ultimate proof can only be achieved by determining the G6PD activity in the erythrocytes, which can be very problematic , especially after blood transfusions in severe hemolytic crises. Alternatively, the G6PD gene is genotyped.

Hemolytic anemia

Congenital hemolytic anemia (s) due to enzyme defects
In addition to G6PD deficiency, there are other congenital hemolytic anemias that are caused by enzyme defects. An example of such anemia is pyruvate kinase (PK) deficiency.
β-thalassemia (beta thalassemia)
β-thalassemias are also congenital hemolytic anemias. In contrast to the anemia caused by enzyme defects, β-thalassemias are caused by a mutation in the β chain of hemoglobin . In contrast to the G6PD deficiency, they are a hemoglobinopathy . In typical β-thalassemias, hemolytic anemia does not appear until 3–9 months, when the mutation in the beta chain of hemoglobin can show its effects due to the change in hemoglobin synthesis from fetal hemoglobin ( HbF ) to adult hemoglobin ( HbA ) . The course of hemolytic anemia due to β-thalassemia is usually more gradual than that of G6PD deficiency.
α-thalassemia (alpha thalassemia)
Like β-thalassemia.
Autoimmune hemolytic anemia (n)
In the various forms of autoimmune hemolytic anemia, the antibodies that lead to hemolysis by means of immune processes can usually be identified. This detection of antibodies is not possible in the case of G6PD deficiency, since hemolysis takes place here by a different mechanism.
Drug-induced hemolytic anemia (n)
These hemolytic anemias can be very difficult to distinguish from G6PD deficiency. An indication can be given by the origin of the person concerned, whereby drug-induced hemolytic anemia can also occur in people from regions with G6PD deficiency. A reliable differentiation can only be made by measuring the G6PD activity.

Other anemias

Iron deficiency anemia
This anemia is typically not associated with hemolysis. As a rule, it also develops gradually. Typically, there are small erythrocytes ( MCV less than 70 fL) and a lack of iron and ferritin in the serum or plasma.
Bleeding anemia
This anemia can be differentiated from the anemia of G6PD deficiency by identifying a source of bleeding . In addition, bleeding anemia usually shows no signs of hemolysis.
Folic Acid Deficiency Anemia
This anemia is characterized by abnormally large erythrocytes ( MCV greater than 100 fL). It develops gradually and usually has no signs of hemolysis.
Vitamin B 12 - Deficiency Anemia
This anemia is characterized by abnormally large erythrocytes ( MCV greater than 100 fL). It develops gradually and usually has no signs of hemolysis.

The Kelley-Seegmiller syndrome must also be distinguished .

Historical

The lack of glucose-6-phosphate dehydrogenase as the cause of the long-known clinical picture of favism or haemolytic anemia as a result of primaquine exposure was first identified in 1956. The first cDNA sequence of the G6PD was described in 1981.

literature

  • RK Ohls, RK Christensen: Chapter 20. Diseases of the blood. In: RE Behrman, RM Kliegman, HB Jenson: Nelson Textbook of Pediatrics. 17th edition. Saunders, Philadelphia 2003, ISBN 0-7216-9556-6 .
  • M. Right, HA Pearson: Chapter 295. Hemolytic Anemias. In: JA McMillan, CD Deangelis, RD Feigin, JB Warshaw, FA Oski: Oski's Pediatrics: Principles and Practice. 3. Edition. Lippincott Williams & Wilkins, 1999, ISBN 0-7817-1618-7 .

Databases

  • Glucose-6-phosphate dehydrogenase deficiency.  In: Online Mendelian Inheritance in Man . (English), as of July 21, 2006, information in English .
  • Entrez protein from the National Center for Biotechnology Information (NCBI), National Library of Medicine (NLM), USA record 120731 . As of September 19, 2006. Information in English .
  • SwissProt database, University of Geneva, Switzerland. Data record P11413 . As of September 19, 2006. Information in English .
  • Human Gene Mutation Database (HGMD), Institute of Medical Genetics, Cardiff, UK data set G6PD . As of September 23, 2006. Information in English .

Individual evidence

  1. ↑ Diabetes and Co: Mankind is becoming increasingly multimorbid. In: Deutsches Ärzteblatt. June 8, 2015.
  2. ↑ iss.it: Connection of hydroxychloroquine and G6PD. Retrieved May 9, 2020 .
  3. ↑ Chloroquine Is Not a Harmless Panacea for COVID-19. March 23, 2020, accessed on May 9, 2020 .
  4. ↑ German doctors Verlag GmbH, editing German doctors Journal: hydroxychloroquine at COVID-19 possibly with increased ... April 22, 2020, accessed on May 9, 2020 .
  5. ↑ Glucose-6-phosphate dehydrogenase deficiency - knowledge for medical professionals. Retrieved on May 9, 2020 (German).
  6. ↑ THE COVID-19 PANDEMIC AND HEMOGLOBIN DISEASES (DE) _Version III (Updated). Retrieved May 9, 2020 .
  7. ↑ Rapporto ISS COVID-19 n. 14/2020 German version - Interim guidance for the appropriate support of people with enzymopenia G6PD (favism) in the current SARS-CoV-2 emergency scenario. Version April 14, 2020 - ISS. Retrieved May 9, 2020 .
  8. ↑ The Belgian AFMPS warns about the risk of hemolysis associated with the use of hydroxychloroquine. Retrieved May 9, 2020 .
  9. ↑ T. Takizawa, IY Huang, T. Ikuta, A. Yoshida: Human glucose-6-phosphate dehydrogenase: primary structure and cDNA cloning. In: Proc Natl Acad Sci USA . 83 (12), 1986, pp. 4157-4161.
  10. ↑ G. Martini, D. Toniolo, T. Vulliamy et al. a .: Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. In: EMBO J . 5 (8), 1986, pp. 1849-1855.
  11. ↑ RJ Dern, IM Weinstein, GV Leroy, DW Talmage, AS Alving: The hemolytic effect of primaquine. I. The localization of the drug-induced hemolytic defect in primaquine-sensitive individuals. In: J Lab Clin Med. 43 (2), 1954, pp. 303-309. PMID 13130947 .
  12. ^ RJ Dern, E. Beutler, AS Alving: The hemolytic effect of primaquine. II. The natural course of the hemolytic anemia and the mechanism of its self-limited character. In: J Lab Clin Med. 44 (2), 1954, pp. 171-176. PMID 13184224 .
  13. ^ E. Beutler, RJ Dern, AS Alving: The hemolytic effect of primaquine. III. A study of primaquine-sensitive erythrocytes. In: J Lab Clin Med. 44 (2), 1954, pp. 177-184. PMID 13184225 .
  14. ↑ EL Kimbro Jr., MV Sachs, JV Torbert: Mechanism of the hemolytic anemia induced by nitrofurantoin (furadantin); further observations on the incidence and significance of primaquine-sensitive red cells. In: Bull Johns Hopkins Hosp. 101 (5), 1957, pp. 245-257. PMID 13472250 .
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