What is Dubin–Johnson syndrome?
Dubin–Johnson syndrome is a form of autosomal recessive disorder that increases the level of conjugated bilirubin in the blood serum without elevating the liver enzymes. This condition is much alike Rotor syndrome, as it is closely related to the hepatocytes’ inability to secrete conjugated bilirubin in the bile.
Symptoms of Dubin–Johnson syndrome
The Dubin–Johnson syndrome is normally asymptomatic. However, the disorder can be diagnosed during early infancy by carrying out certain laboratory tests. The most common Dublin-Johnson syndrome symptoms are:
- Sporadic phases of jaundice which causes yellowing of the white portion of the eyes and the skin.
- Pain in the right hypochondrium
- Enlargement of liver
- Tenderness of the liver
- Black liver
- Presence of dark pigmentation in the parenchymal cells
- Presence of bilirubin in the urine
- Increased levels of conjugated bilirubin in blood
Genetics of Dubin-Johnson syndrome
Mutations in the gene ABCC2 causes Dubin-Johnson syndrome. The ABCC2 gene sends out necessary instructions for making a type of protein called MRP2 or the multidrug resistance protein 2. The MRP2 protein helps to excrete waste products from the body by transporting them out of the kidneys, liver, placenta or intestine. The MRP2 transports bilirubin out of the liver cells into the bile, which is a digestive fluid synthesized by the liver. Bilirubin is produced when the old red blood cells are broken down. It has an orange-yellow coloration.
ABCC2 gene mutations create a version of MRP2 which is unable to effectively pump waste substances out of body cells. These mutations mainly affect the transportation process of bilirubin into bile. This result in the accumulation of large amounts of bilirubin in the body which creates a condition called hyperbilirubinemia. This accumulation of bilirubin in the body causes yellowing of the skin and white portions of the eyes which is characteristically found in people suffering from Dubin-Johnson syndrome.
Pathophysiology of Dubin-Johnson syndrome
The conjugated hyperbilirubinemia is caused by defective exogenous and endogenous transport of anionic conjugates from the hepatocytes into bile. Deposition of pigments in the lysosomes results in blackening of the liver.
Causes of Dubin-Johnson syndrome
Dubin–Johnson syndrome is a type of autosomal recessive disorder, which means that both the copies of the gene in each cell produce mutations. Both the parents of an individual having this autosomal recessive condition carry one copy of this mutated gene. However, the parents generally do not display the symptoms and signs associated with this disorder.
Dubin–Johnson syndrome disturbs the body’s natural ability to remove bilirubin from liver. In cases where the bilirubin is not processed properly, it starts to build up in the blood, resulting in the yellowing of skin and eyes. When very high quantities of bilirubin are accumulated in the body, it can even lead to damaging of the brain and other bodily organs.
People having Dubin-Johnson syndrome tend to have lifelong recurrent episodes of mild jaundice that can be worsened by:
- Alcohol
- Pregnancy
- Birth control pills
- Infections
- Environmental factors which affect the liver
Dubin-Johnson syndrome Diagnosis
There are some tests which can help to diagnose this syndrome. These are:
- Liver biopsy
- Serum bilirubin
- Blood tests for checking liver enzyme levels
- Tests for checking urinary coproporphyrin levels
A significant feature of Dubin-Johnson syndrome is the odd ratio between the various byproducts resulting from heme biosynthesis.
- The ratio between coproporphyrin III and coproporphyrin I in subjects unaffected by Dubin-Johnson syndrome is approximately 3-4:1.
- In patients suffering from Dubin-Johnson syndrome, the ratio between coproporphyrin III and coproporphyrin I is reversed from that in normal patients and the proportion of coproporphyrin I is 3 to 4 times higher than coproporphyrin III. A study of the urine porphyrins demonstrates a normal level of coproporphyrin. However, the presence of coproporphyrin I isomer is almost 80%, unlike the 25% occurrence in unaffected patients.
During post-mortem autopsy, the liver is found to have a dark pink or black coloration resulting from pigment accumulation.
There is a good amount of canalicular multi-drug resistant protein which helps to transfer bilirubin to bile canaliculi. An isoform of the canalicular multi-drug resistant protein is confined to the apical hepatocyte membrane, which allows the transmission of glucuronide and helps in the conjugation of glutathione back into blood.
High levels of gamma-glutamyl transferase (GGT) aid in the diagnosis of pathologies which involves biliary obstruction.
Dubin-Johnson syndrome Treatment
Treatment for Dubin-Johnson syndrome will depend on the underlying causes for the disorder and may include various processes like phototherapy, albumin infusion, exchange transfusions as well as drug therapy. Phototherapy is used to treat physiological jaundice as well as pathological jaundice caused by erythroblastosis fetalis after the preliminary exchange transfusion. The process of phototherapy involves the use of fluorescent light for decomposing bilirubin present in the skin through oxidation. Phototherapy is normally discontinued after the bilirubin levels have come down below 10 mg/dl and continue to fall for 24 hours. However, this method is hardly the only form of treatment for a case of pathological jaundice.
The neonate’s blood is replaced with fresh blood through an exchange transfusion. This removes some of the unconjugated bilirubin in the blood serum. There are several possible signs for exchange transfusions. These include drug toxicity, polycythemia, erythroblastosis fetalis, hydrops fetalis, marked reticulocytosis and jaundice that affects the child within the first 6 hours after birth.
Another method of treating excessive bilirubin levels involves albumin administration (1 g/kg of 25% salt-poor albumin). This provides supplementary albumin which helps in binding unconjugated bilirubin and may be done around 1 to 2 hours before the exchange. It may also be used to replace a portion of plasma present in the transfused blood.
Drug therapy is rare and normally involves administration of phenobarbital to the mother prior to delivery and also to the newborn child several days after the delivery. The phenobarbital drug aids in the stimulation of the hepatic glucuronide-conjugating system.
Dubin-Johnson syndrome Prognosis
Prognosis of Dubin-Johnson syndrome is good and in most cases treatment of this disorder is unnecessary. Most of the patients do not show any visible symptoms in their lives and lead a happy, normal life. Life span of a person having Dubin-Johnson syndrome is also normal. Some newborns have symptoms of cholestasis. Hormonal contraceptive pills and pregnancy may aggravate conditions like jaundice and icterus.
Dubin-Johnson syndrome is an autosomal recessive disorder that can be easily dealt with. In many occasions people having this disorder do not display the symptoms their entire lives. Patients are commonly known to lead a long and happy life.
References:
http://www.rightdiagnosis.com/d/dubin_johnson_syndrome/treatments.htm
http://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome
http://en.wikipedia.org/wiki/Dubin%E2%80%93Johnson_syndrome
http://www.nlm.nih.gov/medlineplus/ency/article/000242.htm
http://emedicine.medscape.com/article/928711-overview#showall