G6PD Deficiency in the Newborn Clinical Presentation

Updated: Jun 25, 2020
  • Author: Lawrence C Wolfe, MD; Chief Editor: George T Griffing, MD  more...
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Presentation

History

The majority of people with glucose-6-phosphatase dehydrogenase (G6PD) deficiency may remain clinically asymptomatic. However, neonates can present with exacerbated neonatal jaundice. Episodes of acute hemolytic anemia following exposure to an oxidative agent or with chronic nonspherocytic hemolytic anemia can occur. [4, 16, 28, 29, 30, 26, 31]

Patients may experience episodes of intravascular hemolysis and consequent anemia, triggered by infections, medicines that induce oxidative stresses, fava beans, and ketoacidosis. Hemolysis begins 24-72 hours after exposure to oxidative stress. Patients with severe hemolysis present with weakness, tachycardia, jaundice, and hematuria.

The clinical presentation of G6PD deficiency includes a spectrum of hemolytic anemia ranging from mild to severe hemolysis in response to oxidative stress. The likelihood of developing hemolysis and its severity depend on the level of the enzyme deficiency, which in turn depends on the G6PD variant. [4, 5]

Neonatal jaundice/hyperbilirubinemia 

G6PD deficiency is one of the major risk factors for severe neonatal jaundice. [10] Jaundice most often appears within the first 24 hours of life, usually earlier than physiologic jaundice but later than jaundice seen in blood group alloimmunization.   

Jaundice can be very severe in some G6PD-deficient babies, especially in association with prematurity, infection, and/or environmental factors (such as naphthalene-camphor balls used in babies' bedding and clothing). Coexistence of a mutation in the uridyl transferase gene (UGT1A1; the same mutations that are associated with Gilbert syndrome) can also exacerbate neonatal jaundice. [18]

Hazardous hyperbilirubinemia, defined as a total serum bilirubin of greater than 30 mg/dL, is a rare event, occurring in 5 per 100,000 live births after universal bilirubin screening. G6PD deficiency is the leading cause of hazardous hyperbilirubinemia when an etiology is identified. [35]  A retrospective study evaluating neonates readmitted to the hospital for hyperbilirubinemia indicated G6PD deficiency to be the most frequent and severe risk factor for hyperbilirubinemia in regions where prevalence of the deficiency is high. [36]

Some G6PD-deficient neonates, if undiagnosed soon after birth, could present later in the first week of life with generalized jaundice, poor feeding, lethargy, breathing difficulty, or seizures. If inadequately managed, neonatal jaundice associated with G6PD deficiency can lead to kernicterus and permanent neurologic damage. [28, 29, 30, 26, 31, 18]

Acute hemolytic anemia 

Acute episodic hemolytic anemia occurs on exposure to oxidative stress, as in association with certain medications and chemicals, infections, and ketoacidosis, and after ingestion of fava beans. Hemolysis usually begins 24-72 hours after exposure to oxidative stress. In cases of severe hemolysis, patients present with malaise, irritability, weakness, jaundice, tachycardia due to moderate to severe anemia, and often dark urine (cola- or tea-colored) due to hemoglobinuria (usually within 6-24 hours). The onset can be extremely abrupt, especially with favism in children.

Acute hemolysis is usually self-limited and resolves within 8-14 days due to the compensatory production of young red blood cells, which have high levels of G6PD enzyme. Young red blood cells are not vulnerable to oxidative damage and, hence, limit the duration of hemolysis. Acute renal failure is a rare complication of acute hemolytic anemia in adults. [4, 18]

Chronic nonspherocytic hemolytic anemia

A small percentage of G6PD-deficient patients have chronic nonspherocytic hemolytic anemia of variable severity. G6PD Brighton, G6PD Harilaou, and G6PD Serres are included in this category. [1, 18, 37]

The patient with chronic nonspherocytic hemolytic anemia is usually a male with a history of neonatal jaundice who may present with anemia, unexplained jaundice, or gallstones later in life. Although they have chronic hemolysis, the patients are also vulnerable to acute oxidative damage on exposure to an oxidative agent. [18]

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Physical Examination

Physical examination findings may be normal in patients with G6PD deficiency. Jaundice, pallor, and splenomegaly may be present in patients with severe hemolysis. Patients may have right upper quadrant tenderness due to hyperbilirubinemia and cholelithiasis.

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