What is the most likely cause of jaundice and abnormal liver function studies in a 7-day-old African American boy with sepsis due to Escherichia coli (E. coli), hyperbilirubinemia, and elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels?

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Differential Diagnosis

  • Single most likely diagnosis
    • B. Inadequate NADPH production for oxidative injury protection: This patient's presentation with jaundice, elevated liver enzymes, and hemolytic anemia (indicated by low hemoglobin and elevated indirect bilirubin) in the context of a bacterial infection (Escherichia coli sepsis) is suggestive of glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an X-linked recessive disorder that leads to inadequate NADPH production, making red blood cells more susceptible to oxidative stress and hemolysis, especially during infections or exposure to certain medications or foods. The condition is more common in African American males, which aligns with the patient's demographics.
  • Other Likely diagnoses
    • A. Inability to metabolize galactose to glucose: This refers to galactosemia, a condition that can present with jaundice, liver dysfunction, and sepsis in the neonatal period, especially after the introduction of lactose-containing feeds (breast milk or formula). However, the direct Coombs test being negative and the specific pattern of liver enzyme elevation and hemolysis might be less typical for galactosemia.
    • E. Single amino acid substitution within the beta-globin chain: This refers to sickle cell disease, which can cause jaundice and hemolytic anemia. However, the acute presentation with sepsis and specific laboratory findings might not fully align with the typical initial presentation of sickle cell disease.
  • Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)
    • Infections leading to hemolysis or liver dysfunction (e.g., congenital infections like toxoplasmosis, rubella, cytomegalovirus, herpes simplex), although the blood culture growing Escherichia coli and the clinical context provided point more directly towards a complication of the identified sepsis rather than a separate infectious cause.
    • Other causes of neonatal sepsis that could lead to multi-organ dysfunction, including the liver and hematologic systems.
  • Rare diagnoses
    • C. Loss-of-function mutation in the WAS gene: This refers to Wiskott-Aldrich Syndrome, a rare X-linked recessive disorder characterized by eczema, thrombocytopenia, and recurrent infections. While it could potentially present with some overlapping features, the specific combination of jaundice, hemolytic anemia, and liver enzyme elevation in the context of sepsis is less typical.
    • D. Mutation in proteins linking the red blood cell membrane to its cytoskeleton: This refers to hereditary spherocytosis or other membrane disorders, which can cause hemolytic anemia but might not fully explain the liver enzyme elevation and the specific context of sepsis and jaundice in this patient.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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