Rotor Syndrome - Symptoms, Diagnosis, and Treatment

Introduction:

The liver is the largest vital organ of the human body. The primary function of the liver is filtration, digestion, storage of vitamins and minerals, protein synthesis, metabolism, and detoxification.

The gallbladder is a small pear-shaped organ located on the right side of the abdomen, just below the liver. The gallbladder's main function is to store bile and concentrate it and release them at the time of need. The gall bladder squeezes the bile into the small intestine with many ducts known as bile ducts. Bile helps in fat digestion.

Bilirubin is a yellowish substance that is formed by the breakdown of hemoglobin in the liver and excreted in bile. This bilirubin travels to the liver and is stored in the bile duct. This is the pigment that makes feces brown. Many disorders occur when there is an imbalance in levels of bilirubin. One of which is hyperbilirubinemia. Increased levels of bilirubinemia cause syndromes like rotor syndrome and Dubin Johnson Syndrome.

What Is Rotor Syndrome?

Rotor syndrome is a relatively rare benign autosomal recessive bilirubin disorder syndrome. It is said to be the initial stages or milder form of Dubin Johnson syndrome, both of which occur due to increased levels of conjugated bilirubin. Rotor syndrome is distinguished from Dubin johnson syndrome by the absence of hepatic pigmentation.

This inherited condition is caused by characterized elevated levels of bilirubin in the blood; these bilirubin levels cause yellowish discoloration of the skin, mucous membrane, and whites of the eye, leading to jaundice which is the only symptom of this condition. There are two types of bilirubin in the body: toxic-unconjugated bilirubin and nontoxic-conjugated bilirubin. This syndrome results in the build-up of both kinds of bilirubin, but the majority is conjugated bilirubin.

How to Differentiate Rotor Syndrome From Dubin Johnson Syndrome?

• It is very much important to distinguish Rotor syndrome from another disease that causes increased levels of bilirubin in the bloodstream.

• Normal levels of alkaline phosphatase and gamma-glutamyl transpeptidase help to differentiate Rotor from other disorders with biliary obstruction.

• Dubin Johnson syndrome has similar symptoms, but these two can be distinguished by abnormal urinary coproporphyrin excretion and normal liver histology in the Rotor. Also, hyperpigmentation of the liver is seen in DJs, but the liver and associated structures are normal in Rotor syndrome.

• The plasma disappearance of an injected substance is seen delayed with no extra secondary rise in Rotor syndrome, but this is significant in Dubin johnson syndrome.

• Rotor syndrome is a milder form of DJs.

• Liver biopsy can show a significant difference in Rotor and Dubin johnson syndrome by the presence of hyperpigmentation seen in the liver in DJs.

What Causes Rotor Syndrome?

• Mutations of SLCO1B1 and SLCO1B3 genes are responsible for Rotor syndrome.

• These mutations provide instructions for creating similar proteins, called organic anion transporting polypeptide 1B1 and organic transporting polypeptide 1B3, which are found in liver cells and are essential for digestion and excretion of bilirubin from the body.

• The mutations which cause this syndrome leads to non-functional proteins in the liver or lead to the absence of them.

• Due to their absence, the liver fails to take up bilirubin and its excretion from the body.

• Thus rise in bilirubin occurs in the body leading to jaundice.

What Are the Signs and Symptoms of Rotor Syndrome?

Patients with Rotor syndrome are usually asymptomatic:

• Yellowing of Whites of Eyes: Conjunctival icterus condition where whites of the eye become yellow. Most commonly seen in liver patients.

• Yellowing of Skin: Intermittent jaundice comes and goes; not stable.

• Jaundice: Yellowish discoloration of mucous membrane, skin, and whites of an eye due to increased levels of bilirubin in the bloodstream.

• Pruritus (Skin Itching): Pruritus is an itch or sensation and discomfort which makes an individual scratch.

How Is the Diagnosis Made for Rotor Syndrome?

• General medical and physical examination includes examining the vitals and checking for pain tenderness or any kind of swelling. Tap some areas of the body to check for the presence of air, liquid, or solid structures.

• Genetic Testing: Genetic testing involves examining the DNA sequences and database that carries instructions for body functions.

• Laboratory findings such as blood and urine tests- abnormal enzyme/coenzyme activity tests, hyperbilirubinemia, porphyria, and conjugated hyperbilirubinemia tests. Mild elevations in alanine transferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase are seen.

• Imaging tests such as CT (computed tomography) scan, MRI (magnetic resonance imaging), and ultrasound imaging can diagnose Rotor syndrome but can help in ruling out causes of extrahepatic biliary obstruction.

• In Rotor syndrome, the Gall bladder is visualized on oral cholecystography, which is not seen in DJs.

• Liver biopsy is rarely done in this syndrome, but it helps in diagnosing and differentiating the syndrome from other disease-causing hyperbilirubinemia.

What Is the Treatment Provided for Rotor Syndrome?

• Rotor syndrome does not affect life expectancy; it is not associated with morbidity or mortality.

• Most patients affected with Rotor syndrome are born to consanguineous (individuals descendent from the same ancestor) couples, and the diagnosis leads to identifying consanguinity.

• Differentiation of Rotor syndrome with other diseases is very important, which may help in the treatment and avoid unwanted intervention and stress.

• Reassuring and calming the patients and educating them about the benign condition of Rotor syndrome is very important.

What Is the Differential Diagnosis for Rotor Syndrome?

Many other disease conditions also cause hyperbilirubinemia which may get misdiagnosed with Rotor syndrome; they are:

• Dubin Johnson syndrome (a condition which is characterized by jaundice).

• Gilbert syndrome (a mild condition in which the liver fails to process bilirubin).

• Familial intrahepatic cholestasis (a condition that causes progressive liver disease).

• Extrahepatic biliary obstruction (blockage of normal flow of bile).

• Crigler-Najjar syndrome (a condition with high levels of bilirubin toxicity).

• Hemolysis (destruction of the liver blood cells).

• Viral hepatitis (infection of the liver due to viral infection).

• Autoimmune hepatitis (infection of the liver due to autosomal recessive condition).

• Wilson's disease (a rare inherited condition that causes copper accumulation in the liver).

• Drug-induced hepatotoxicity (increase in toxicity of the liver due to excessive drug intake).

• Cirrhosis (end-stage liver disease).

• Alpha 1 antitrypsin deficiency syndrome.

• Hemochromatosis (causes the body to absorb too much iron from food).

• Cholestasis in pregnancy.

Conclusion:

Rotor syndrome is an autosomal recessive inherited syndrome. It is a benign condition that stays lifelong with no effect on life expectancy. No treatment or management is required for the individuals. No mortality or morbidity is associated with Rotor but can occur if any other life-threatening disease occurs along with this condition. The absence of proteins in this condition is responsible for the detoxification of certain drugs, so caution has to be taken in taking certain drugs to avoid drug toxicity.