Clinical Cases

Gilbert’s Syndrome and its Homoeopathic Treatment

Sinchan Das
Written by Sinchan Das

Dr. Sinchan Das discusses Gilbert’s Syndrome including the physiology and biochemistry involved and gives a case summary of a cured case.

Gilbert’s syndrome (GS), a neglected disease of modern health science is usually harmless, but can sometimes harm an individual seriously.

Gilbert’s syndrome is a common genetic hepatic disorder, caused by the inheritance of an abnormal gene, i.e. UGT1A1, characterized by elevated levels of unconjugated bilirubin in the blood stream, due to the reduced activity of the enzyme glucuronyltransferase, responsible for the conjugation of the bilirubin and a number of other lipophilic molecules along with several drugs also. Gilbert’s syndrome is more common in males than females and more in  stressed persons. We know that changes in the UGT1A1 gene causes this potentially benign inherited hepatic disorder,  and that UGT1A1 provides instructions for making the bilirubin uridine diphosphate glucuronyltransferase (Bilirubin-UGT) enzyme, found primarily on the liver cells. The bilirubin-UGT performs a chemical reaction essential for detoxification, called glucuronidation. During this reaction, the enzyme transfers glucuronic acid to unconjugated bilirubin and finally that to conjugated bilirubin.  The principal actionof glucuronidation is to make substances water soluble for removal purposes.

Gilbert’s syndrome occurs worldwide but some mutations occur more often in particular populations. In many populations, the most common genetic change that results into GS is known as UGT1A1*28 and occurs in the promoter region, which controls the production of the bilirubin-UGT. This genetic change impairs enzyme production. However, this change is uncommon in Asian populations and affected Asians often have a mutation that changes a single protein building block in the bilirubin-UGT enzyme. This type of mutation, known as the missense mutation, resulting in reduced enzymatic function. Now come to the topic pathophysiology of GS.  Uridine diphosphoglucuronate transferase (UDPGT) is the enzyme responsible for conjugating bilirubin into bilirubin monoglucuronide and bilirubin diglucuronide; it is therefore the rate-limiting step of bilirubin conjugation.

This occurs in the endoplasmic reticulum of hepatocytes. There are 5 exons that ultimately lead to production of uridine diphosphoglucuronate. Exon 1 determines substrate specificity. Among the 13 different types of exon 1, Exon 1a encodes variable region for UDPGT-1A1, the enzyme responsible for conjugation of bilirubin. Upstream to exon 1a, there is a TATAA box promoter region, normal sequence of which is A[TA]6TAA.                                                                                                                                                       Page no. 01

But the people with Gilbert’s syndrome inherit a different sequence of the promoter region, i.e. A[TA]7TAA.


Other mutations have been discovered within the coding regions of the UDPGT-1A1, leading to the Gilbert’s phenotype. There is some evidence suggesting that the patients with UDPGT-1A1*28 may have abnormal metabolism of protease inhibitor which leads to deficiency in the endogenous protease inhibitor, like α1- antitrypsin, which may lead to several diseases affecting respiratory system, hepato- biliary system and gastro-intestinal system in varying degree. There is also evidence suggesting that these mutations provide a protective effect in the development of Hodgkin’s lymphoma and cardio-vascular disorders.

The question arises, what are the influences of this abnormal mutation?  There is no answer found regarding this question. However, I will try to postulate the probable influencing factors briefly. To undergo mutation, DNA needs to go through the ‘break and repair mechanism’ influenced by several endogenous and exogenous factors. To continue the discussion in details we should offer a  snapshot  about the UGT1A1 gene.

The uridine diphosphate glucuronyltransferase (UGT) enzymes are a superfamily of enzymes responsible for the glucuronidation of target substances. The transfer of glucuronic acid renders xenobiotics and other endogenous compounds water soluble, allowing for their biliary or renal elimination. The UGT family is responsible for the glucuronidation of many compounds, including hormones, flavonoids and environmental mutagens. Liver is the site where most of the members of UGT family are principally expressed, as well as in other tissues also such as intestinal, gastric or breast tissues. One of the transcripts encoded by the UGT1A locus is UGT1A1, which is at the furthest 3’ end of the UGT1A exon 1 region. UGT1A1 is expressed hepatically, as well as within the colon, intestine and stomach. Main functions of UGT1A1 lies within the liver, where it is the sole enzyme responsible for the metabolism of bilirubin, the hydrophobic breakdown product of ‘haem’ catabolism. UGT1A1 alleles have also been associated with the development of various cancers. Along with bilirubin and pharmaceuticals, UGT1A1 enzyme have been seen to glucuronidate Benzo () pyrene-trans-7, 8-dehydradiol, a precursor to the potent carcinogen Benzo (α) pyrene-7, 8- dehydradiol- 9,10- epoxide, found in charbroiled food, coal tar and cigarette smoke. They have also been noted to glucuronidate oestradiol, as well as 2- amino- 1- methyl- 6- phenylimidazo (4, 5) pyrene (PhIP), another carcinogen present in cooked meat. UGT1A1 therefore exhibits a protective effect against benzo (α) pyrene & PhIP mediated carcinogenicity and modulates the level of oestradiol within the body.

The *28 allele has been shown to increase the risk of developing colorectal cancer and breast cancer across multiple studies in Chinese and Asian populations. There is also evidence suggesting that UGT1A1*28 allele may offer protection from cardio-vascular disorders. Bilirubin is a known antioxidant and is capable of preventing plaque formation, leading to atherosclerosis. Multiple studies have found a link between low bilirubin concentrations and an increased risk of cardio-vascular disease, though this association may be affected by cofounders, such as obesity or hypercholesterolaemia. This is about UGT1A1 gene in short                     

For mutation, it needs to under the ‘damage and repair mechanism’ of DNA repeatedly, so, from this point of view it is clear to us that there might be some influences, which provoke the DNA for this damage and repair procedure, resulted into this mutation. Now the next question is what are the influences? Purpose of this damage and repair mechanism of DNA is to modulate themselves according to the concerned atmosphere for the purpose of avoiding the harmful effects of those atmospheres. We can say easily from the previous part of our discussion that the probable causes of the mutation are——

  • The ancestors of the particular patient were exposed to excessive stress, which may results into oxidative damage to the tissues dangerously; due to which, level of dopamine, aldosterone, cortisol and other anti- stress hormones are elevated in considerable amount within the blood. For that reason bilirubin concentration in the blood become elevated, as bilirubin exhibits an anti-oxidant property; or
  • 2) the ancestors suffered from the diseases, which can be prevented by the help of this mutation.

So, we can see from this discussion that UGT1A1*28 mutation reveals a long continued suffering of not only a patient, rather his or ancestors also.

Now, come to the part, i.e. clinical presentation of the patients with Gilbert’s syndrome, generally complicated with other disorders, like haemolytic anaemia, fatty liver, gastro-oesophageal reflux disorder, irritable bowel syndrome and some neurological disturbances:

Sr. No.Known, EffectsSymptoms
01 

Functional disturbance of liver

·        Chemical sensitivity

·        Excessive allergic reactions

·        Drug intolerance

·        Toxic feeling

02 

Gastroparesis

·        Nausea  ⇒   Vomiting, Decreased appetite  ⇒ Easily satiety ⇒  Loss of appetite

·        Abdominal bloating/Flatulence

·        Heartburn

·        Gastro-oesophageal reflux disorder

·        Indigestion

·        Hypoglycaemia

·        Loss of appetite ⇒   Weight loss⇒   Low body weight

03Essential tremor·        Tremor/Trembling of hand
04 

Hyperbilirubinaemia

·        Jaundiced eyes, i.e. yellowish discolouration of the upper bulbar conjunctiva    ⇒  Itchiness in the eyes.

·        Jaundice ⇒   Itchiness

·        High coloured urine

·        Clay coloured stool

·        Excessive anger

05 

Hepatic enlargement/ Swollen liver

·        Pain and tenderness in right hypochondrium

·        Pain in the region of Gall bladder

·        Dull abdominal pain

06 

Immune suppression

·        Catches cold easily

·        Easily affected by diseases

07Gall stones/ Cholelithiasis/ Cholecystitis·        Light coloured stool

·        High coloured urine

·        Jaundice

·        Itching

·        Abdominal pain

·        Nausea

·        Vomiting

·        Back pain

·        Abdominal bloating

·        Fatty food intolerance

·        Sweating

08 

Hypothyroidism

·        Fatigue

·        Tiredness

·        Depression

·        Dry skin

·        Cold hands & feet

·        Chilliness

·        Irregular bowel habit

·        Constipation

·        Poor memory

·        Deficient concentration

·        Anxiety

·        Dysphagia

·        Low body temperature

·        Lump in the throat

·        Feeling of anti- social

·        Pain in joints

·        Mood swing

·        Environmental allergies

·        Pain in eyes

·        Sinusitis

·        Light sensitivity

·        Dizziness

·        Headache

·        Night sweat

09 

Chronic Fatigue Syndrome

·        Fatigue

·        Myalgia

·        Brain-fag

·        Gastro-intestinal disturbances

·        Headaches

·        Sore throat

·        Insomnia

·        Low body temperature

·        Chest pain

·        Sinus pain

·        Rhinitis

·        Back pain

·        Loose stools

10 

Candida

·        Food intolerance

·        Headache

·        Brain-fag

·        Myalgia

·        Joint pain

·        Sinusitis

·        Fatigue

·        Allergies

·        Chemical sensitivity

·        Irregular bowel disorder

·        Mood swings

·        Numbness and tingling in extremities

·        Night sweat

·        Gastro- intestinal disturbances

·        Irritability

·        Anger

·        Poor memory

·        Chest pain

·        Dizziness

 

Homoeopathic treatment of Gilbert’s syndrome

At first I am going to discuss, a case of Gilbert’s syndrome that came to me. Other cases also had a similar outcome.

CASE                                      

PATIENT’S DETAIL
NAME:                                XXXXXXXX

AGE:                                    42 Years

SEX:                                    Male

OCCUPATION:                 Employee at Eastern Railways

About the author

Sinchan Das

Sinchan Das

Dr. Sinchan Das is a homoeopathic physician and health scientist from
India. He is working with several complex issues regarding health
science, including how homoeopathic medicines work, pathophysiology of
homoeopathic medicines and effectiveness of homoeopathic medicines on a genetic level. He has received many national and international awards in recognition of his work.

1 Comment

  • Wonderful presentation of a rare disease in an unique scientific manner. Why should not you arrange some seminars with this author.

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