Conjugated Hyperbilirubinemia in Infancy (Mitochondrial DNA Depletion Syndrome, Liver)

Excerpt

A male infant was born at term after a normal pregnancy and was normal in early infancy. The mother in a previous marriage had 1 normal child, a girl, now 6 years old and healthy. The infant under discussion is the second born with her current spouse; the first born, a male, developed progressively worsening liver failure and died at age 9 months, and an etiologic diagnosis had not been established. This the second male infant presented at 3 months with poor feeding, irritability, lethargy, and jaundice. The infant had hepatomegaly of 4 cm. Investigations demonstrated hypoglycemia, conjugated hyperbilirubinemia, increased levels of alkaline phosphatase (574 U, normal 110–320 IU/L), aspartate aminotransferase (190 IU, normal 20–60 IU/L), alanine aminotransferase (144 IU, normal 6–50 IU/L), and gamma glutamyl transpeptidase (GGT) (624), an amino acid analytic result that was abnormal but not specific and in keeping with liver disease, normal result from organic acid analysis, increased α-fetoprotein (300,000 ng/mL), normal levels of very long-chain fatty acids, increased lactate (7.6 mmol/L), no ketosis, increased ammonia (40 μmol/L), prolonged prothrombin time, normal total carnitine, markedly decreased free carnitine (0.8, normal 30.3–40.5 nmol/L), and a normal acyl carnitine profile. All studies for an infectious etiology were negative. Muscle biopsy examined by hematoxylin and eosin, histochemistry, and electron microscopy was normal. Liver biopsy showed mitochondrial DNA depletion in the liver but not in fibroblasts. A mutation in the deoxyguanosine kinase (dGK) gene was excluded. …