A 6-month-old baby born to a consanguineously married couple, presented with jaundice since day 3 of life (total biluribin of 22.6 mg/dL with indirect fraction of 21.8 mg/dL) along with abnormal movements in the form of stiffening of limbs and arching of body. Review of medical records showed no features suggestive of hemolysis, liver cell failure, hypothyroid state and breast milk jaundice. Trial of phenobarbitone therapy was also found to be ineffective in bringing down bilirubin levels.

Now at 6 months of age, with regular home phototherapy for the past 5 months, baby weighed 5 kg and was irritable. Develop-mental history revealed delayed attainment of milestones with social smile at 5 months and partial head control at 6 months. Examination revealed deep icterus with staining of palms and soles and signs of kernicterus. Routine blood and urine tests were normal. Serum bilirubin was 25 mg/dL (indirect fraction of 23.8 mg/dL) and other liver function tests were normal. A screening for TORCH infection was negative. A second trial of phenobarbitone therapy was also in- effective.

The diagnosis of CNS-I was considered in our case based on clinical characters - severe persistent unconjugated hyperbilirubinemia developing early in neonatal period with no response to two trials of phenobarbitone therapy, early development of features of kernicterus and by excluding other conditions like breast milk jaundice, hemolysis and hypothyroid state. CNS type II is the most important differential diagnosis. The major differentiating characteristic between the two types of Crigler-Najjar syndrome is the response to drugs that induce activity of cyto-chrome P450 enzymes like pheno-barbitone that causes a significant decline in the serum bilirubin of patients with type II diseases(4). However, differentiating Crigler-Najjar syndrome type I from type II solely on the basis of response to phenobarbitone can sometimes be misleading and confirmatory diagnosis rests on demonstration of absence of UGT activity in liver and mutation analysis and these test are complicated and not routinely available(4). In our case, extracted DNA samples of the patient and parents are stored for future analysis in definitive diagnosis. Crigler-Najjar syndrome type I was considered in our case by its classical clinical presentation, non-response to two trials of phenobarbitone therapy and by a process of exclusion of other conditions causing persistent unconjugated hyperbilirubinermias in infancy. Currently the treatment of CNS-I consists of phototherapy followed by liver transplantation(2), Tin-mesoporphyrin, hepatocyte transplantations(5), ursodeoxy-cholic acid, bilirubin oxidase, antioxidants, calcium supplements, clofibrate, flumecinol, chlorpromazine and urine alkalinization have been tried in CNS-I. The most exiting new therapy discussed is the gene therapy(5).

M.L. Kulkarni,
Naveen Reddy C.,
Department of Pediatrics,
J.J.M. Medical College,
Davangere 577 004,
Karnataka,
India.

1. Moghrahi N, Clarke DJ, Burchell B, Boxer M. Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syn-drome type I: Implication in carrier detection and prenatal diagnosis. Am J Hum Genet 1993; 53: 722-729.

2. Jansen PLM. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr 1999; 158 (suppl 2): S89-S94.

3. Chowdhury J R, Walkoff A, Chowdhary NR, Arias IM. Hereditary jaundice and disorders of bilirubin metabolism. In: Scriver CR, Beaudet AI, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 7th edn. New York: Mc Graw-Hill, 1995; pp. 2161-2208.

4. Lee WS, Mc Kiernan PJ. Beath SV, Preece MA, Baty D, Kelly DA, et al. Bile bilirubin pigment analysis in disorders of bilirubin metabolism in early infancy. Arch Dis Child 2001; 85: 38-42.

5. Fox IJ, Chowdhury JR, Koufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, et al. Treatment of the Crigler-Najjar Syn-drome type I with hepatocyte transplantation. N Engl J Med 1998; 14: 338: 1422-1425.