Bilirubin adsorption therapy and subsequent liver transplantation cured severe bilirubin encephalopathy in a long-term survival patient with Crigler-Najjar disease type I.
Crigler-Najjar disease (CN) type I is characterized by persistent unconjugated hyperbilirubinemia from birth. The male patient here was diagnosed with this disease as a neonate and had been treated by phototherapy. At age 16 he suddenly developed generalized convulsions, followed by impaired cognitive function. The serum level of bilirubin was extremely high (total bilirubin: 41.7 mg/dl) and there were no other detectable causes responsible for the metabolic encephalopathy. He received bilirubin adsorption therapy several times, and the bilirubin encephalopathy improved in response to the fall in the serum level of bilirubin. After this he underwent a successful liver transplantation in Australia, and recovery of his mental faculties was satisfactory. Within the subsequent 3 years epileptic abnormal discharges on the electroencephalogram disappeared. Phototherapy alone can not prevent the rise in the serum level of bilirubin in adolescent or adult patients with CN type I, therefore such patients tend to experience life-threatening bilirubin encephalopathy. To save patients with the acute onset type of bilirubin encephalopathy, sufficient bilirubin adsorption followed by liver transplantation appears to be the most recommended therapeutic approach. (+info)
Kernicterus in full-term infants--United States, 1994-1998.
Kernicterus is a preventable life-long neurologic syndrome caused by severe and untreated hyperbilirubinemia during the neonatal period. High levels of bilirubin are toxic to the developing newborn. In full-term infants, hyperbilirubinemia symptoms include severe jaundice, lethargy, and poorfeeding. Features of kernicterus may include choreoathetoid cerebral palsy, mental retardation, sensorineural hearing loss, and gaze paresis. Kernicterus is not a reportable condition in the United States, and its prevalence is unknown; however, a pilot registry at a Pennsylvania hospital documented 90 cases in 21 states from 1984 to June 2001 (L. Johnson, Pennsylvania Hospital, Philadelphia, personal communication, 2001). This report summarizes case histories of four full-term, healthy infants who developed kernicterus and underscores that to prevent kernicterus, newborns must be screened and promptly treated for hyperbilirubinemia. (+info)
Bilirubin-albumin binding and free bilirubin.
The relevance of plasma bilirubin-albumin binding and, in particular, the nonalbumin-bound or "free" bilirubin concentration to neonatal bilirubin toxicity is controversial. The pivotal role that "free" bilirubin played in the bilirubin toxicity that occurred following administration of sulfisoxazole or benzyl alcohol to jaundiced newborns, and the correlation of "free" bilirubin with bilirubin-induced changes in the auditory brainstem response are strong support for measuring "free" bilirubin when evaluating neonatal jaundice. Reliable methods for measuring "free bilirubin" are available, and population reference values are needed to help determine its proper clinical use. (+info)
P-glycoprotein and bilirubin disposition.
P-glycoprotein (Pgp), an ATP-dependent plasma membrane efflux pump, is expressed in abundance on the luminal aspect of brain capillary endothelial cells and astrocytes of the blood-brain barrier where it limits the passage of a variety of lipophilic substrates into the central nervous system. This review summarizes current evidence characterizing (1) unconjugated bilirubin as a potential substrate for Pgp and (2) the ontogeny of Pgp expression at the blood-brain barrier and apical brush border epithelium of the gastrointestinal tract, findings that may provide insights regarding the disposition of bilirubin in immature subjects. (+info)
Bilirubin brain toxicity.
Bilirubin is toxic in most biological systems tested. Several mechanisms have been suggested for this toxic effect, including inhibition of enzyme systems and inhibition of cell regulatory reactions (protein/peptide phosphorylation). The identity of the basic mechanism(s) has not been conclusively proven, but inhibition of peptide phosphorylation, perhaps mediated or modulated by lysine at the active site(s), appears to be compatible with many of the observations currently found in the literature. Bilirubin entry into brain is facilitated by drug displacement of bilirubin from its albumin binding, reduced albumin binding capacity, increased brain bloodflow, increased permeability of the blood-brain barrier, and other factors. The rate of bilirubin entry into brain, as well as the degree of retention and rate of clearance from brain, depends on which of these circumstances are operative. It is as yet unclear whether the mechanism responsible for increased brain bilirubin is important for toxicity. The mechanism for preferential localization of bilirubin to the basal ganglia in kernicterus is also not known. Bilirubin appears to distribute differentially to brain subcellular compartments and is oxidized in brain by an enzyme localized on the inner mitochondrial membrane. This enzyme is found both in neurons and in glia, but appears to be more active in the latter. The activity increases with postnatal age, and is subject to genetic variability in animals. The enzyme is cytochrome c-dependent. It is as yet not clear whether the activity of this enzyme serves a brain-protective effect in severe hyperbilirubinemia. (+info)
Bilirubin and the auditory system.
The auditory system is highly sensitive to bilirubin toxicity. Damage to the auditory nervous system includes auditory neuropathy or auditory dyssynchrony and auditory processing problems which may occur with or without deafness, hearing loss. Auditory dysfunction may occur in children with or without other signs of classical kernicterus. Bilirubin selectively damages the brainstem auditory nuclei, and may also damage the auditory nerve and spiral ganglion containing cell bodies of primary auditory neurons. The inner ear, thalamic and cortical auditory pathways appear to be spared. Noninvasive auditory neurophysiological tests such as the auditory brainstem response (ABR) or brainstem auditory response (BAER) play an important role in the early detection of bilirubin-induced auditory and central nervous system dysfunction in the neonate. (+info)
Criteria for treatment of neonatal jaundice.
Treatment of neonatal hyperbilirubinemia is usually based on the measurements of total serum bilirubin levels. Based on empirical data, it is generally recommended to start phototherapy at lower levels in low birth weight and very low birth weight infants than in term infants, but no general agreement exists on exact limits. Treatment criteria in preterm infants do not, however, have the same empirical backing as in term infants. The very low and extremely low birth weight infants are more susceptible to bilirubin toxicity. However, bilirubin may function as an antioxidant and enzyme inducer in these infants. Several other different approaches to establish treatment criteria have also been suggested, and a summary of these are presented and discussed. With the exception of measurement of unbound bilirubin, very few of these approaches have been validated in routine clinical settings. However, unbound bilirubin is at present mainly used also as a parameter to be evaluated in relation to total bilirubin values. The present treatment criteria result in a considerable overtreatment particularly of term infants. However, with a more relaxed attitude toward neonatal hyperbilirubinemia by health care professionals, kernicterus is again reported in term infants. Because the basic mechanisms of bilirubin toxicity as well as the relative significance of the maximum serum bilirubin level compared to the duration of hyperbilirubinemia are not known, individual assessment of a newborn infant's tolerance for hyperbilirubinemia is difficult. Major changes in the empirically developed criteria for treatment of hyperbilirubinemia in the newborn are therefore not justified in the near future. For term infants, the search for validated criteria for follow-up of jaundiced infants after discharge are therefore more important than revision of existing criteria for phototherapy. (+info)
OBSERVATION OF CHILDREN'S TEETH AS A DIAGNOSTIC AID: II. DEVELOPMENTAL DIFFICULTIES REFLECTED IN ENAMEL AND PIGMENT CHANGES IN TEETH.
Current interest in tetracycline staining of teeth and other enamel defects led to this review. In the handicapped child structural defects that were seen in the dental enamel may provide a most accurate etiological clue. The method of determining the time of insult is described. Comments are made on seven states in which enamel dysplasia may be frequently observed. A simple means of identifying tetracycline pigment incorporated in dental enamel is outlined. Bilirubin staining of teeth is also shown and warnings are given about the indelible nature of these pigments. (+info)