Name: Shruti Kadam

Roll no: 113

Biochemistry Semester 6 Paper 1 Unit 3 Assignment

Carbohydrate metabolism : G6PD DEFICIENCY

Glucose-6-phosphate dehydrogenase is an enzyme found in the cytoplasm of all cells in the
body. It is a housekeeping enzyme that plays a vital role in the prevention of cellular damage
from reactive oxygen species. It does this by providing substrates to prevent oxidative
damage. Erythrocytes are particularly vulnerable to ROS due to their role in oxygen transport
and the inability to replace cellular proteins as mature cells. Inherited deficiencies of glucose-
6- phosphate Dehydrogenase can result in acute hemolytic anemia during times of increased
reactive oxygen species production. In particular, anti-malarial agents have a strong
association with inducing hemolytic anemia in patients with Glucose-6-phosphate
dehydrogenase deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme found in the cytoplasm of all cells
in the body. It is a housekeeping enzyme that plays a vital role in the prevention of cellular
damage from reactive oxygen species (ROS). It does this by providing substrates to prevent
oxidative damage. Erythrocytes are particularly vulnerable to ROS due to their role in oxygen
transport and inability to replace cellular proteins as mature cells. Inherited deficiencies of
G6PD can result in acute hemolytic anemia during times of increased ROS production. This
may be caused by stress or exposure to certain foods that contain high amounts of oxidative
substances, for example, fava beans, or certain medications. In particular, anti-malarial
agents have a strong association with inducing hemolytic anemia in patients with G6PD
deficiency.
ETIOLOGY
• The Gd gene codes for the G6PD enzyme.
• This gene is located on the long arm of the X chromosome and therefore follows X-
linked inheritance.
• Deficiency of G6PD may be due to mutations that change the protein structure and
therefore reduce its activity, or the amount of enzyme produced.
• There are currently 186 known human G6PD mutations, and most are point mutations
affecting a single nucleotide.
• None of the mutation patterns seen in humans cause complete inactivation of G6PD
since this would be lethal to a developing embryo.

EPIDEMIOLOGY
• G6PD is the most common human enzyme defect known, affecting upward of 400
million people worldwide.
• Men are more commonly affected than women due to X-linked inheritance. It is most
prevalent in tropical and subtropical areas.
 • There is evidence to suggest that G6PD deficiency is protective against
uncomplicated malaria, but not severe malaria cases. The protective mechanism for
G6PD deficiency and malaria is still being investigated.
• G6PD deficiency is more common in people of African, Mediterranean, or Asian
descent, likely owing to its suggested protective effect from malaria.

PATHOPHYSIOLOGY
• G6PD is the catalyst in the rate-limiting first step of the pentose phosphate pathway,
which uses glucose-6-phosphate to convert nicotinamide adenine dinucleotide
phosphate (NADP) into its reduced form, NADPH.
• In red blood cells, NADPH is critical in preventing damage to cellular structures
caused by oxygen-free radicles.
• It does this by serving as a substrate to the enzyme glutathione reductase.
• Reduced glutathione can be used to convert hydrogen peroxide to water and prevent
damage to cellular structures, particularly the cell wall of red blood cells (RBCs) since
they have limited capacity for repair once mature.
CLINICAL MANIFESTATION
• Although most patients remain asymptomatic throughout their life, the clinical
manifestations of G6PD deficiency depend on the age of the patient.
• In new-borns, G6PD deficiency is recognized as a serious risk factor for the
development of neonatal hyperbilirubinemia.
• Neonates with G6PD deficiency are two times more likely to develop
hyperbilirubinemia than the general population, and approximately 20% of
kernicterus cases are associated with G6PD deficiency.
• Symptoms of kernicterus in a new born include lethargy, extreme sleepiness, and poor
muscle tone.
• Although rare, G6PD deficiency should be considered in neonates, who develop
jaundice in the first 24 hours of life, who have a history of a sibling with neonatal
jaundice, or have a bilirubin level greater than the 95th percentile.
• In adults, common symptoms and exam findings of G6PD deficiency include those of
hemolytic anemia or possibly red blood cell sequestration by the spleen.
• Some of these manifestations include pallor, jaundice, fatigue, splenomegaly, and
dark urine.

EVALUATION
• NEONATAL EVALUATION:
In new born infants, assess the presence of jaundice by first examining the skin for a yellow
appearance in a room that is well lit. More objective measurements include obtaining total
serum bilirubin (TSB) or transcutaneous bilirubin (TcB) in new-borns. An hour-specific
bilirubin nomogram can be used to risk-stratify new born patients with elevated bilirubin
levels to help determine the appropriate treatment.
Although screening tests for G6PD deficiencies are available, they are not routinely
performed in the United States; however, screening should be considered in new-borns that
have severe jaundice resistant to phototherapy or who have a family history or ethnicity
suggestive of G6PD deficiency. The most common screening method includes a rapid
fluorescent spot test to detect the generation of NADPH from NADP. Screening can also be
performed by quantitative spectrophotometric analysis.
• CHILDREN AND ADULT EVALUATION:
The evaluation of older patients presenting with complications of G6PD deficiency begins
with a complete history to include new medications and screening for a family history of
similar symptoms. It is also important to evaluate for possible infection, as the stress of
infection may trigger a hemolytic event in patients with G6PD deficiency.
Laboratory studies include a complete blood count, bilirubin levels, reticulocyte count, serum
aminotransferases, and lactate dehydrogenase. A peripheral blood smear may show signs of
hemolysis such as schistocytes.

TREATMENT / MANAGEMENT
• NEONATES
In the neonatal patient, treatment focuses on managing jaundice and preventing kernicterus.
This includes phototherapy based on standard published guidelines. In severe cases, an
exchange transfusion may be necessary.
• CHILDREN AND ADULTS
In older patients, management depends primarily on the overall clinical picture. Less severe
presentations may be managed with supportive care and discontinuation and avoidance of the
offending agents. Treat any infections as indicated by history and exam. More severe cases
may require transfusions.

DIFFERENTIAL DIAGNOSIS
Many disease processes may resemble the pathophysiology of G6PD deficiency. Therefore
differential considerations should include:
• Autoimmune hemolytic anemia
• Bilirubin conjugation disorders (e.g., Gilbert syndrome)
• Hemolytic disease of the new born
• Hereditary spherocytosis
• Sickle cell anemia
• Thalassemia
Reference: https://www.ncbi.nlm.nih.gov/books/NBK470315/
https://www.healthline.com/health/glucose-6-phosphate-dehydrogenase-deficiency