Lack of Deafness in Crigler–Najjar Syndrome Type 1: A Patient Survey

Abstract

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

Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease

“…1b, Case 5). Contrary to other studies [53,54], we could not identify a relationship between age and compliance with phototherapy as a plausible explanation. The progressive rise in bilirubin is likely influenced by several physiological variables.…”

“…Crigler and Najjar's classic description preceded the advent of effective phototherapy, and all of their patients developed brain injury and eventually died [19]. The combined data from four recent surveys [37,[52][53][54] suggest that 23-42% of CND patients suffer neurological injury ranging from mild to severe, 28-50% of patients will need one or multiple exchange transfusions, and 9-38% die of complications related to the disease. In contrast, we had no brain injuries or deaths extending over 200 patient-years and did not perform a single exchange procedure since we began caring for children with CND in 1989.…”

Disease burden of Crigler–Najjar syndrome: Systematic review and future perspectives

“…Of these, three were general review articles, one of which also included results of an international survey . Of the remaining 25 publications, eight were case series or case reports, 10 were retrospective cohorts, three were prospective cohorts, two were RCTs, and two were cross‐sectional studies . Nineteen primary publications were specific to CNS, while six comprised patients with various inherited metabolic disorders including CNS .…”

“…The primary clinical feature of CNS is unconjugated hyperbilirubinemia, which ranges from 4 to 45.2 mg/dL and exhibits distinctive patterns related to patient age and clinical circumstance (refer to succeeding discussions).…”

Crigler–Najjar syndrome II and pregnancy outcome

“…Th e cut-off value of bilirubin above which kernicterus occurs is not well defi ned due to the rarity of this condition, in association with pregnancy, although levels of Ͻ 10 mg/dl are advocated. Reports in the literature suggest that patients with type I CNS have neonates aff ected with hearing loss, cerebellar syndrome, developmental delay and speech delay (Suresh and Lucey 1997). Adverse neonatal outcomes have been reported with untreated CNS type 2 with high maternal serum bilirubin (17.0 -21.8 mg/dl) manifesting in neonatal quadriplegia (Taylor et al 1991).…”