Internal Medicine

Meulengracht's disease

Synonyms

Gilbert-Meulengracht's disease

Gilbert syndrome

Definition - what is Meulengracht's disease?

Meulengracht's disease (Gilbert-Meulengracht's disease, Gilbert syndrome) is a harmless disease that is caused by a congenital metabolic disorder of the liver. The disease is passed on to children through parents.

A gene mutation causes bilirubin, the breakdown product of red blood cells, to be metabolized more slowly and excreted in the bile. As a result, the plasma level of bilirubin rises and leads to various symptoms.

causes

The cause of Meulengracht's disease is a so-called functional hyperbilirubinemia. This means that the bilirubin level in the blood plasma has risen above the normal level due to a liver dysfunction. Normally, hemoglobin, the main component of red blood cells, is converted to bilirubin in the liver and excreted in the bile through the intestines. An important step in this process is the connection of the bilirubin with glucuronic acid (conjugation) so that the bilirubin becomes water-soluble and the bile can be released in the conjugated form.

In Meulengracht's disease, the conjugation of bilirubin is disturbed by an enzyme defect. The enzyme responsible, UDP-glucuronoyltransferase, only works to about 30 percent. This makes the whole process much slower and excess, unconjugated bilirubin accumulates in the liver and blood (hyperbilirubinemia).

Read more about the topic: Hemoglobin of the liver

diagnosis

The doctor diagnoses Meulengracht's disease through a blood test. An increased concentration of the indirect (unconjugated) bilirubin in the blood plasma with otherwise normal liver and blood values indicate the disease.

Furthermore, the mutation in the UDP-glucuronyltransferase gene can be detected using the polymerase chain reaction (PCR). The symptoms of Meulengracht's disease can be misinterpreted by both the patient and the doctor and interpreted as a severe chronic liver disease (e.g. due to hepatitis B or hepatitis C), which is why a genetic test is appropriate for clear detection in case of doubt.

Inheritance

Meulengracht's disease is an inherited disease in which a genetic mutation leads to a reduced activity of the enzyme UDP-glucuronyltransferase. This is an autosomal recessive inheritance, which means that the mutation must be present on both chromosomes (of mother and father) for the disease to break out in the child. Children whose parents or one of the parents are affected by the disease have a significantly higher risk of developing Meulengracht's disease.

Read more on the topic: Genetic Diseases

What can be the accompanying symptoms of Meulengracht's disease?

Meulengracht's disease is a relatively harmless disease that rarely manifests itself through symptoms. The patients may suffer from abdominal pain, which is mainly perceived as an uncomfortable feeling of pressure in the right upper abdomen.

Indigestion, nausea and gas can also occur. Further symptoms are depressive moods, exhaustion and a general malaise, as well as headaches, migraine attacks and loss of appetite.

In some cases, the rise in the bilirubin concentration in the blood leads to jaundice, which is known as intrahepatic jaundice. Jaundice manifests itself as an intense yellow coloration of the sclera (the whites of the eyes) and the skin, but is otherwise painless. In addition, patients have colorless, white stools.

The symptoms are more pronounced with hunger and long periods of fasting, but the consumption of alcohol or cigarettes can also trigger the symptoms. However, there is no correlation between the severity of symptoms and the level of excess bilirubin in the blood plasma.

stomach pain

Abdominal pain, which occurs more or less severely in temporary bouts, is a typical accompanying symptom in Meulengracht's disease. In rare cases, the abdominal pain occurs in combination with indigestion, gas or even nausea with a metallic taste in the mouth. Symptoms get worse after consuming alcohol or nicotine.

Flatulence

In addition to stomach pain and nausea, flatulence can also be a symptom of Meulengracht's disease. The flatulence can cause the abdomen to become very bloated (meteorism). Furthermore, the affected people suffer from a feeling of fullness and stomach tumors. Eating gas can make symptoms worse. Home remedies such as caraway seeds and fennel tea, but also sufficient exercise and regular exercise, help against flatulence.

fatigue

In rare cases, Meulengracht's disease patients suffer from permanent fatigue, physical exhaustion and difficulty concentrating. In severe cases, doctors speak of chronic fatigue syndrome or fatigue. This is an extraordinary amount of tiredness that has no relation to previous physical activities.

depression

As a result of Meulengracht's disease, depression or depressive moods can occur in the patient. Patients feel hopeless and completely unmotivated. They are overwhelmed by simple activities in everyday life. At the first signs of depression, it is best to contact the treating doctor immediately, as the depression will quickly disappear with the right treatment.

Treatment and therapy

Meulengracht's disease is basically not curable because the metabolic disorder is genetically inherited and congenital. Most of the time, those affected get along well without treatment and do not need any therapy. In severe cases, the symptoms and gastrointestinal complaints can be treated with medication, whereby the side effects of the prescribed medication are often more severe than the symptoms themselves. The symptoms usually appear in bouts and go away quickly on their own even without treatment.

However, those affected can ensure that the symptoms occur only rarely and in a mild form. Especially the discolored eyes caused by jaundice are extremely stressful for the patients. With sufficient drinking, the body is properly “flushed” and the bilirubin that has accumulated can be excreted more quickly through the kidneys.

The symptoms are intensified by certain behaviors. An appropriate lifestyle, in which the patient does not avoid smoking, alcohol and long periods of hunger, as well as getting enough sleep, prevents an increase in the concentration of bilirubin in the blood and the associated symptoms. This allows you to get the disease under control and the health impairment remains low.

Bilirubin level

The concentration of indirect bilirubin is increased in Meulengracht's disease and is above the normal value at 2-5 mg / dl. Indirect bilirubin is bilirubin that has not yet been conjugated with glucuronic acid in the liver and is therefore not soluble in water.

In the blood, indirect bilirubin is bound to a specific transport protein, albumin. The doctor will take a blood sample to check the bilirubin level. Laboratory diagnostics determine the total bilirubin value and the conjugated bilirubin value in a blood sample in the plasma (cell-free blood) or in the serum (plasma without coagulation factors) of the patient. The concentration of indirect bilirubin results from the difference between the total value and the value of the conjugated bilirubin.

Duration and forecast

Usually Meulengracht's disease is completely harmless and the patients live completely unaffected by the disease. Drug therapy with enzyme inducers (e.g. phenobarbital or rifampicin) is usually not necessary and is rarely prescribed due to the undesirable side effects. Unfortunately, only a few patients experience symptoms and life expectancy is generally not reduced by Meulengracht's disease, as the hyperbilirubinemia does not damage the internal organs.

Which drugs are involved in metabolism?

In Meulengracht's disease, UDP-glucuronyltransferase is restricted in its function. Since the enzyme is important for the breakdown of other drugs in addition to the excretion of bilirubin, the disease can change the effect of drugs and lead to undesirable interactions.

The drugs that are broken down by UDP-glucuronyltransferase include various HIV drugs (indinavir or atazanavir), cholesterol-lowering drugs (atorvastatin and simvastatin) and pain relievers with the active ingredients ibuprofen and paracetamol.

Can i take ibuprofen?

The active ingredient ibuprofen is broken down in the liver by UDP-glucuronyltransferase. In Meulengracht's disease, this process takes place more slowly and an overdose of ibuprofen can occur. In general, poisoning with ibuprofen requires relatively high doses that are not so easy to achieve, which is why the intake of ibuprofen is considered safer than paracetamol in patients with Meulengracht's disease. Nevertheless, the intake should be discussed with the doctor, as overdosing can cause kidney damage.

Can i take paracetamol?

As a precaution, patients with Meulengracht's disease must not take paracetamol, as a toxic intermediate product can occur due to the inadequate metabolism with UDP-glucuronyltransferase. Above a certain concentration, the toxin can no longer be excreted and binds to liver cell proteins, causing irreversible liver damage and ultimately liver failure.

Will the pill work for me?

Estradiol and ethinylestradiol, the estrogen components of oral contraceptives (“pill”), are also broken down by the affected enzyme UDP-glucuronyltransferase. As a result, the pill is broken down more slowly in Meulengracht's disease. However, the estrogen concentration of the preparations that are on the market today is relatively low, which is why they can be taken after consultation with the attending gynecologist.

What is the best diet if I have Meulengracht's disease?

In general, people with Meulengracht's disease can eat normally and only have to pay attention to a few things. Prolonged periods of starvation or fasting cause bilirubin levels in the blood to rise and the symptoms of Meulengracht's disease to worsen. For this reason, patients must make sure that they are eating enough and regularly. Even with morning sickness due to pregnancy, affected pregnant women must remember that they consume enough calories despite the vomiting and thus do not provoke an attack of symptoms.

Patients must also make sure that they eat a balanced diet and not too one-sided, as low-fat foods can also raise the bilirubin level. The right diet can make a big difference and have a positive effect on the symptoms of Meulengracht's disease. A sufficient supply of water causes the kidneys to work harder and accelerates the detoxification of the body. This can lower the level of bilirubin in the blood. Fresh fruits and vegetables provide fiber and vitamins that can help against rapid fatigue and fatigue. Freshly brewed peppermint tea or peppermint lollipops can be helpful against recurring nausea when you are out and about.

You can find out more about healthy eating here

What effect does sport have on my illness and which sport can I do?

In general, people with Meulengracht's disease are not physically impaired in any way and can practice any sport that suits them. Sport and physical activity unfortunately do not contribute to a decrease in bilirubin levels in the blood. However, regular exercise can have a positive effect on the symptoms caused by Meulengracht's disease.

Above all, rapid fatigue and persistent exhaustion can be managed well with endurance training such as running, cycling or swimming. It is important, however, that patients make sure they consume adequate carbohydrates and calories before and after running, as fasting may worsen nausea and yellowing of the skin.

Excessive exercise and heavy physical activity, in particular, can also worsen the symptoms of Meulengracht's disease. The muscle contains the protein myoglobin, which serves to store oxygen and is similar to hemoglobin in the blood. Myoglobin is broken down in the liver in a similar way to hemoglobin via biliverdin, which is why the bilirubin concentration increases due to the increased breakdown of muscle cells during exercise.

In the event of problems or worsening of symptoms due to exercise, it is best to discuss with their doctor which sport is best for them and how it can have a positive effect on the disease and the symptoms associated with it.

How does alcohol affect the disease?

Alcohol is broken down in the liver by the enzyme alcohol dehydrogenase. The consumption of alcohol damages the liver tissue and the function of the liver is further restricted. As a result, the levels of indirect (conjugated) and direct (non-conjugated) bilirubin in the blood rise. Alcohol increases the bilirubin level in Meulengracht's disease considerably and patients should therefore strictly avoid drinking alcoholic beverages.

Read more on the topic: Elevated liver values

homeopathy

There are also alternative medicine and homeopathic methods available to alleviate the symptoms of Meulengracht's disease. A special Chinese tea made from various herbs, the Yin Zhi Huang tea, can help the liver to excrete excess bilirubin. A number of homeopathic remedies, such as Carduus marianus, Crotalus and Chionanthus virginica, have a supportive effect against jaundice. A doctor specializing in homeopathy or naturopathy can individually address the patient's complaints and create a suitable homeopathic treatment plan.