Crigler-Najjar syndrome type I. Severe unconjugated hyperbilirubinemia with
intense jaundice appears in the first 3 days of life and persists through
the neonatal period. Diffusion of unconjugated (lipid-soluble) bilirubin
into the brain may be favored by a damaged blood-brain barrier (e.g.,
hypoxia, hyperosmolality), but also by prematurity and the presence of
hypoalbuminemia or highly protein-bound drugs (e.g., sulfonamides).
Kernicterus usually presents in the first week of life (although it may
occur at any time, especially during the neonatal period, but is not limited
to this period) with lethargy, loss of the Moro reflex, and poor feeding.
Left untreated, it may progress to opisthotonus, signs of increased
intracranial pressure (e.g., bulging fontanelle, high-pitched crying),
seizures, and stiffness. Affected infants often die in the first weeks or
months of life secondary to kernicterus, others survive with little or no
neurologic sequelae. In survivors, these neurologic signs often do not
resolve or recur after an initial improvement and may finally result in
bilateral choreoathetosis, seizures, mental retardation, hearing loss,
speech anomalies, and extrapyramidal signs. The neurologic sequelae reflects
injury to basal ganglia, corpus subthalamicum, thalamus, globus pallidum,
putamen, cerebellar and cranial nerve nuclei, and hippocampal structures.
Phototherapy (450-nm wavelength light) and emergent exchange transfusion
often are required in the first days of life. The only treatment for
Crigler-Najjar syndrome type I is liver transplantation.