Unconjugated Hyperbilirubinemia Clinical Presentation

Updated: Sep 29, 2020
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
  • Print


Increased bilirubin production

Ineffective erythropoiesis (ELB production) is characterized by the onset of asymptomatic jaundice.

Impaired conjugation of bilirubin

Crigler-Najjar (CN) syndrome type 1

Apart from jaundice, the affected infant usually appears healthy at birth. Jaundice develops in the first few days of life and rapidly progresses by the second week; therefore, exchange transfusion is warranted despite phototherapy. A family history that includes consanguinity, relatives with severe jaundice without hemolysis, or relatives with evidence of liver disease and a history of exchange transfusion further supports the diagnosis.

Because of its autosomal recessive transmission, consanguinity is a risk factor for Crigler-Najjar syndrome type 1.

Crigler-Najjar syndrome type 2

Usually, no clinical symptoms except for jaundice are reported with this disease entity. However, bilirubin encephalopathy has been reported.

Gilbert syndrome

Diagnosis is made in patients who have no past history of liver disease and manifest only jaundice on clinical examination.

At least 30% of patients with Gilbert syndrome are asymptomatic, although nonspecific symptoms, such as abdominal cramps, fatigue, and malaise, are common. No relationship exists between the abdominal symptoms and plasma bilirubin levels.

Abdominal symptoms may be multifactorial, with underlying anxiety probably playing an important role. Although it is true that not all patients with Gilbert syndrome and abdominal symptoms are anxious, they nonetheless appear to have organic-type discomfort that is hard to characterize and frequently eludes diagnosis.

Neonatal jaundice


Physiologic jaundice is clinically obvious in 50% of neonates during the first 5 days of life.


In maternal serum jaundice (Lucey-Driscoll syndrome), jaundice occurs during the first 4 days of life.


Physical Examination

Crigler-Najjar syndrome

Type 1

Patients with Crigler-Najjar syndrome type 1 appear healthy at birth, with no signs of liver disease. Patients may present with evidence of kernicterus, the clinical manifestations of which are hypotonia, deafness, oculomotor palsy, lethargy, and, ultimately, death.

Type 2

Apart from jaundice, physical findings are usually normal in Crigler Najjar syndrome type 2, with no signs of hemolysis or liver disease.

Gilbert syndrome

Apart from mild jaundice, physical examination findings in people with Gilbert syndrome are normal.