Crigglar-Najjar syndrome is rare genetic disorder impairs bilirubin metabolism to cause hyperbilirubinemia in newborns.

Crigler-Najjar syndrome causes nonhemolytic jaundice due to lack of UDP-glucuronosyltransferase from UGT1A1 gene mutation.

Bilirubin metabolism includes storage, conjugation, and excretion into bile.

It is classified into two types as:

Crigler-Najjar Syndrome Type 1

Crigler-Najjar Syndrome Type 2

CNS1 from lack of UGT1A1 enzyme for bilirubin conjugation causes hyperbilirubinemia.

CNS2 results from mutations causes partial UGT1A1 enzyme deficiency in severity based on specific mutations and enzymatic activity.

Hyperbilirubinemia can occur shortly after birth and lead to irreversible brain damage if severe.

The severity and presentation are dependent on the specific UGT1A1 gene mutation on chromosome 2q37 determine enzyme activity.

Rare Crigler-Najjar syndrome has an incidence rate of 0.6 to 1 in 1 million newborns. Parasitic diseases in lesser-developed countries cause biliary obstruction.

Increased risk of neonatal hyperbilirubinemia includes prematurity, East Asian/Mediterranean ethnicity, breastfeeding, and blood group incompatibilities.

Global prevalence of hyperbilirubinemia varies. Developed countries monitor and manage neonatal jaundice well, while some developing regions lack healthcare access.

Breakdown of heme creates unconjugated bilirubin in macrophages from old/red blood cell destruction.

Issues with metabolic steps can lead to high bilirubin levels in serum, measured as unconjugated or conjugated.

Hepatocytes in liver convert bilirubin to water-soluble conjugated form. Cytosolic enzyme reduces biliverdin to bilirubin for circulation release.

Unconjugated bilirubin overwhelms albumin due to reduced excretion and conjugation.

Unbound bilirubin crosses the blood-brain barrier easily in contrast to bound bilirubin which cannot cross.

The causes of Crigglar-Najjar syndrome are:

Genetic Mutations

Inheritance Pattern

Crigler-Najjar syndrome is due to low UGT enzyme levels from a genetic defect in UGT1A1 gene.

Prognosis for hyperbilirubinemia varies based on the underlying cause.  Prolonged hyperbilirubinemia in low-birth-weight infants can cause green teeth.

Early onset and rapid bilirubin increase may signal severe cause or treatment.

CN2 may be mild or asymptomatic due to residual UGT enzyme activity. Permanent neurological impairment incidence in CN1 patients varies.

Collect details including presenting symptoms, family and medical history to understand clinical history of patient.

Abdominal Examination

Assessment of Dark Urine and Pale Stools

Neurological Assessment

Symptoms are:

Immediate Jaundice

Risk of Kernicterus

Feeding Difficulties

Treatment phase involves managing the underlying liver condition, such as use of antiviral medications for viral hepatitis, and immunosuppressants.

If the excessive bilirubin is increased due to red blood cell breakdown, the treatment involves discontinuation of medications that cause hemolysis and manage autoimmune disorders.

Orlistat synergizes with calcium phosphate to increase effectiveness. It captures bilirubin in the intestines to promote fat excretion in stools.

Intensive phototherapy is preferred in neonatal hyperbilirubinemia treatment for faster response, shorter duration, and fewer complications than conventional methods.

Gastroenterology

Phototherapy is administered using various devices, such as overhead lights or light-emitting pads.

In cases of breastfed infants with hyperbilirubinemia, physician should increase the frequency of breastfeeding sessions.

Hydration may be beneficial in promoting bilirubin excretion through urine and stools.

Potential cure for genetic defect introduces normal UGT1A1 gene through ex-vivo gene transduction into cultured hepatocytes or vector delivery.

Supportive measures include intravenous fluids to maintain hydration to ensure adequate nutrition and manage symptoms.

Appointments with a physician and preventing recurrence of disorder is an ongoing life-long effort.

Gastroenterology

Phenobarbital:

It induces the activity of the residual UGT1A1 enzyme in CNS2 patients to increase bilirubin conjugation and clearance.

Gastroenterology

Clofibrate:

It stimulates UGT1A1 activity to improve bilirubin conjugation.

Gastroenterology

Orlistat:

It binds covalently to the serine residue of the active site of gastric and pancreatic lipases.

Gastroenterology

Phototherapy is used for neonatal hyperbilirubinemia in unconjugated hyperbilirubinemia or physiological jaundice.

Exchange transfusion is used for newborn severe or rapidly increasing hyperbilirubinemia.

Healthy UGT enzyme in transplanted liver lowers serum bilirubin levels.

Plasmapheresis effectively removes excess unconjugated bilirubin in hyperbilirubinemia crisis.

Gastroenterology

In the initial assessment phase, evaluation of patient history, physical examination, and laboratory test to confirm diagnosis.

Pharmacologic therapy is effective in the treatment phase as it includes use of barbiturate, fibrates, and lipase inhibitors.

In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies.

The regular follow-up visits with the gastrointestinal are scheduled to check the improvement of patients along with treatment response.