Lucey–Driscoll syndrome

Overview

Lucey–Driscoll syndrome is a rare, transient metabolic disorder that causes severe unconjugated hyperbilirubinemia (high levels of indirect bilirubin) in newborns. It typically presents within the first few days of life and is considered a form of transient familial neonatal hyperbilirubinemia. If not recognized and treated promptly, it can lead to kernicterus, a type of brain damage caused by excessive bilirubin. The syndrome is temporary and usually resolves within the first few weeks of life once the underlying cause is addressed.

Causes

Lucey–Driscoll syndrome is caused by a temporary inhibition of the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for conjugating bilirubin in the liver. The two main contributing factors are:

• Inherited factors – a genetic predisposition that causes reduced UGT1A1 activity in the newborn, often transmitted in an autosomal recessive manner

• Hormonal inhibitors – such as steroidal substances (e.g., pregnanediol) found in maternal breast milk or passed through the placenta, which temporarily suppress UGT1A1 activity

This inhibition leads to an accumulation of unconjugated bilirubin in the blood, resulting in jaundice and potential neurological complications.

Symptoms

Symptoms of Lucey–Driscoll syndrome typically appear within the first few days after birth and include:

• Severe jaundice – yellowing of the skin and eyes due to high bilirubin levels

• Lethargy – decreased activity or poor feeding

• Hypotonia – reduced muscle tone in severe cases

• High-pitched crying – due to neurological irritability

• Seizures or abnormal movements – in extreme cases of bilirubin encephalopathy (kernicterus)

Prompt evaluation is essential to prevent progression to neurological damage.

Diagnosis

Diagnosis of Lucey–Driscoll syndrome involves clinical evaluation and laboratory testing to determine the cause of hyperbilirubinemia. Key diagnostic steps include:

• Total and direct bilirubin levels – to assess the degree and type of jaundice

• – typically normal in Lucey–Driscoll syndrome

• Blood group and Coombs test – to rule out hemolytic causes such as ABO or Rh incompatibility

• Family history – of severe neonatal jaundice or unexplained infant deaths

• Genetic testing – may help identify mutations in the UGT1A1 gene

The diagnosis is often made based on exclusion of other causes and the temporary nature of the condition.

Treatment

Treatment of Lucey–Driscoll syndrome focuses on reducing serum bilirubin levels and preventing complications. Common management strategies include:

• Phototherapy – the primary treatment, using light to convert bilirubin into a water-soluble form that can be excreted

• Exchange transfusion – used in severe cases to rapidly lower bilirubin levels and prevent kernicterus

• Temporary interruption of breastfeeding – if breast milk is suspected to contain bilirubin-inhibiting substances; breastfeeding can usually be resumed after bilirubin levels normalize

• Hydration and feeding support – to promote bilirubin excretion

Close monitoring of bilirubin levels is essential during treatment.

Prognosis

The prognosis for infants with Lucey–Driscoll syndrome is generally excellent if diagnosed and treated promptly. The condition is self-limiting and usually resolves within the first few weeks of life. However, if left untreated, severe hyperbilirubinemia can lead to permanent neurological damage, including hearing loss, cerebral palsy, or intellectual disability. With appropriate medical care and early intervention, most affected infants recover fully without long-term complications.