In this week’s Case Record of the Massachusetts General Hospital, a 9-month-old boy was admitted to the hospital because of fever, diarrhea, and acute liver failure. He had been well, and the results of routine newborn metabolic screening were normal. Examination showed an enlarged liver that was fatty on imaging studies.
The Pediatric Acute Liver Failure (PALF) database shows that the cause of liver failure in children is not determined 49% of the time, although this percentage varies with the age of the child.
Clinical Pearls
• What are the most common causes of liver failure in children?
The differential diagnosis of liver failure in children includes acetaminophen and other drugs, which are the most common identified cause of liver failure (16%), metabolic disorders (10% of the cases), viruses (6%), and ischemia (4%).
• What viruses cause liver failure in children?
Possible infectious causes of acute liver failure include herpes simplex virus, parvovirus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and hepatitis A, B, and C viruses.
Table 2. Differential Diagnosis of the Inborn Errors of Metabolism Associated with Fatty Liver.
Morning Report Questions
Q: How do patients with fatty acid-oxidation disorders present?
A: Fatty acid-oxidation defects (FAODs) and carnitine transport defects are generally suspected in the hypoketotic hypoglycemic patient, or in an infant with acute fatty liver.
Q: What are the pathologic processes that lead to organ dysfunction in children with fatty acid-oxidation defects?
A: Defects in any of the enzymes involved in the fatty acid-oxidation pathway can result in accumulation of unoxidized fatty acids, resulting in intracellular accumulation of fat, and a variety of organ dysfunctions. The FAODs that result in accumulation of long-chain fatty acids present with more severe clinical symptoms (hypoketotic hypoglycemia, liver disease, skeletal myopathy with or without cardiomyopathy, sudden death, and pregnancy complications) than the short-chain and medium-chain FAODs. The latter can have a more subtle onset, including decompensation with fasting, a more variable hypoketotic hypoglycemia, and skeletal myopathy.