Lack of deafness in Crigler-Najjar syndrome type 1: a patient survey.

Abstract

We performed a questionnaire survey about 42 patients with Crigler-Najjar syndrome type 1 who were currently alive. Information was obtained on their age, sex, birth weight, gestation, parental consanguinity, other family members affected, age of onset of jaundice, neonatal and postneonatal bilirubin values, neonatal and postneonatal therapy, problems faced with phototherapy, liver transplantation, current growth status, current neurologic status, and the status of hearing. Patients were between 2 months and 21 years of age. There were 18 males and 24 females. Thirty-nine patients had been born at full term gestation and 3 had been preterm. Jaundice was noted on postnatal day 1 in 34%, between days 2 and 4 in 55%, and after day 11 of life in 11% of patients. In the neonatal period bilirubin values (mean +/- SD) were typically 19.8 +/- 4.5 mg/dL. Eighty-six percent of patients had neonatal peak bilirubin values of >20 mg/dL. Parental consanguinity was present in 44% and a history of Gilbert's disease in one parent was present in 10% of patients. Causes of exacerbations of jaundice reported were respiratory infections, febrile illnesses, vaccinations, fasting, surgery, emotional stress, and noncompliance with treatment. Neonatal therapy consisted of exchange transfusion in 28%, phototherapy in 79%, phenobarbitone in 20%, and cholestyramine, albumin, infusions, and plasmapheresis in one case each. The mainstay of postneonatal therapy was home phototherapy for 10 to 16 hours, primarily at night during sleep, using blue lights or a combination of blue and fluorescent lights. Some patients used innovatively designed phototherapy units. Problems reported with phototherapy were decreased effectiveness with age, poor compliance, restriction of activity and play, inability to travel or take vacations, irritation from eye shades, difficulty keeping eye protection on, difficulties in temperature maintenance, tanning of the skin, embarrassment from the need to be nearly nude during phototherapy, and difficulty in procuring phototherapy lamps. Other therapies that had been tried included oral agar, albumin infusions, antioxidants, acupuncture, bilirubin oxidase, calcium infusions, clofibrate, cruciferous vegetables, cholestyramine, chlorpromazine, flumecinol, plasmapheresis, tin mesoporphyrin, ursodeoxycholic acid, and urinary alkalinization. Fifteen children had undergone liver transplantation (5 auxiliary and 10 orthotopic). All 42 patients are reportedly of normal height and weight. Neurodevelopmental status is said to be normal in 77% of patients. Two patients have kernicterus, 4 have cerebellar symptoms, and 1 each has developmental delay, mild intention tremor, and mild speech delay. Hearing was reported to be normal in 94% of patients. The 2 children with hearing loss have conductive loss from otitis media. With home phototherapy prolonged, survival free of neurologic deficits is possible in Crigler-Najjar syndrome type 1, but there are many problems associated with phototherapy. Avoiding exacerbations of jaundice is an important aspect of management. Liver transplantation offers the prospect of cure but its risk versus benefit ratio is undetermined. Hearing loss was absent in the patients surveyed despite prolonged exposure to high bilirubin levels, which suggests that bilirubin may not be as ototoxic as is commonly believed.