This substance is only eliminated from the body after a chemical reaction occurs in the liver that turns the toxic form of bilirubin (called unconjugated bilirubin) into a non-toxic form called conjugated bilirubin. people with Crigler-Najjar syndrome suffer from a buildup of unconjugated bilirubin in the blood (unconjugated hyperbilirubinemia) in
Crigler-Najjar syndrome is a rare genetic condition occurring in children in which it is difficult to convert the liver-processed material called bilirubin into its water-soluble form (conjugated bilirubin).
In the child’s liver and spleen, the unconjugated bilirubin enters circulation, and then accumulate in other tissues, such as the eyes and skin. Jaundice, ultimately nerve and brain damage are caused by this buildup.
There is an orange-yellow hue of bilirubin, and hyperbilirubinemia causes the skin and whites of the eyes of turn yellow (jaundice). Jaundice is noticeable in Crigler-Najjar syndrome at birth or in infancy.
A disorder called kernicterus, which is a type of brain damage resulted in by the gathering of unconjugated bilirubin in the nerve and brain tissues, may result from extreme unconjugated hyperbilirubinemia.
Kernicterus is often very exhausted (lethargic) and may have a poor tone of the muscles (hypotonia). Signs increased muscle tone (hypertonia), and arching of their backs may occur in these infants. Other neurological problems can result from kernicterus, including involuntary body wrinkles (choreoathetosis), hearing problems, or intellectual disability.
The syndrome of Crigler-Najjar is split into two forms. Form 1 (Crigler-Najjar syndrome 1) is very severe, and affected individuals may die from kernicterus during infancy, although they may live longer with proper treatment.
Less extreme is category 2 (Crigler-Najjar syndrome 2). Kernicterus is less likely to occur in individuals with CN2, and most affected individuals survive into adulthood.
It is estimated that Crigler-Najjar syndrome affects less than 1 in 1 million newborns worldwide.
UGT1A1 gene mutations cause Crigler-Najjar syndrome. This gene provides guidance for the development of an enzyme called bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT), which is mainly found in liver cells and is essential for bilirubin to be eliminated from the body.
A chemical reaction called glucuronidation is performed by the bilirubin-UGT enzyme. The enzyme moves a compound called glucuronic acid to unconjugated bilirubin during this reaction, converting it to conjugated bilirubin. In order to extract it from the body, glucuronidation renders bilirubin dissolvable in water.
UGT1A1 gene mutations that cause Crigler-Najjar syndrome result in the decreased or absent expression of the enzyme bilirubin-UGT. Individuals with CN1 have no enzyme activity, while individuals with CN2 have less than 20% normal function.
The loss of bilirubin-UGT activity reduces unconjugated bilirubin glucuronidation. Then this poisonous agent builds up in the body, causing hyperbilirubinemia and jaundice to become unconjugated.
In an autosomal recessive pattern, Crigler-Najjar syndrome is hereditary, which means both copies of the UGT1A1 gene have mutations in each cell. When a copy of the UGT1A1 gene has a mutation, a less serious disorder called Gilbert syndrome may occur.
Types of Crigler-Najjar Syndrome
In kids, there are two types of Crigler-Najjar syndrome disorder. The liver enzyme called glucuronyl transferase is deficient in patients with type I and the enzyme is reduced in patients with type II.
Phototherapy and the drug phenobarbital (which aids the body to produce more glucuronyl transferase) will handle Type II, and no liver transplantation is needed. In comparison, Type I is more extreme and potentially life-threatening.
Symptoms of Crigler-Najjar Syndrome in Children
The child might suffer from jaundice, and the other following Crigler-Najjar symptoms may happen in a baseline case of this condition:
- Biliary stones-related abdominal pain
Symptoms of the acute stage of the illness are caused by an increase in unconjugated bilirubin and considered medical emergencies:
- With diarrhoea
- Vomiting Over
- A fever
- Slurred speech
- Difficulty Swallowing
- Change in gait, staggering, frequent falling
Diagnosing Crigler-Najjar Syndrome
Among the relatively small population of the Amish and Mennonite groups, Crigler-Najjar syndrome is normal. While Crigler-Najjar is an exceedingly rare condition, 20 per cent of these cases are seen in the Pennsylvania Amish, with only around 100 documented cases worldwide.
On abdominal examination, the baseline disease will show jaundice with no swollen liver or spleen. An increased heart rate, poor circulation of fluids through the organs (perfusion), improper alignment of the eyes, weak gag reflex, and muscle spasms can indicate the acute stage of the disease.
Genetic research can reveal elevated unconjugated bilirubin levels, normal transaminase levels, low albumin levels, and the absence of glucuronyl transferase.
Imaging studies such as an MRI and EEG may be needed, but even after serious injury, an MRI may be common until fatal bilirubin intoxication has occurred. An EEG can assist in confirming intoxication and rehabilitation.
Crigler-Najjar Syndrome Treatment
The primary control of Crigler-Najjar syndrome is phototherapy, in which the infant is exposed to blue LED light in a tanning bed-like apparatus.
The unconjugated bilirubin is broken down by light into compounds that are not harmful to tissues. Phototherapy, however, is a lengthy operation, and it is required 10-12 hours per day.
Prolonged light exposure causes the skin of the infant to thicken, thus raising the need for a more rigorous regimen of phototherapy. The need for phototherapy adversely affects their quality of life considerably.
Actigall, phenobarbital, vitamin E, vitamin C, coenzyme Q, L-carnitine, and creatine are the regular Crigler-Najjar syndrome treatment drugs.
When unconjugated bilirubin exceeds toxic levels, vigorous intravenous fluid hydration, high glucose control, albumin administration, and likely plasma exchange are needed to manage the disease to prevent disastrous neurological consequences.
For Crigler-Najjar patients, liver transplantation is a potentially life-saving procedure. The capacity of a new liver to transform unconjugated bilirubin (which can’t be excreted from the body) into conjugated (which can be excreted from the body) bilirubin.
To avoid liver rejection, immunosuppressant medication (i.e. Prograf ) is needed, and prophylactic medication (Bactrim ®) is used against pneumonia with pneumocystis carinii.
These are typically the only two drugs that Crigler-Najjar patients require a year after transplantation. Patients also have a gene mutation that causes glucuronyl transferase deficiency and the abnormality can still be passed on to their offspring.
A liver transplant helps a patient with Crigler-Najjar to operate without the use of phototherapy and without fear of neurological devastation and death from toxic levels of unconjugated bilirubin.