Biomarker for Gilbert Disease (BioGilbert)
Biomarker for Gilbert Disease (BioGilbert)
Development of a new MS-based biomarker for the early and sensitive diagnosis of Gilbert
 disease from blood
Gilbert syndrome is a mild genetic liver disorder in which the body cannot properly process
 bilirubin, a yellowish waste product that is formed when old or worn out red blood cells are
 broken down (hemolysis). It is inherited as an autosomal recessive trait.

 Individuals with Gilbert syndrome have elevated levels of bilirubin (hyperbilirubinemia),
 because they have a reduced level of a specific liver enzyme required for elimination of
 bilirubin. Most affected individuals have no symptoms or may only exhibit mild yellowing of
 the skin, mucous membranes, and whites of the eyes (jaundice). Jaundice may not be apparent
 until adolescence. Bilirubin levels may increase following stress, exertion, dehydration,
 alcohol consumption, fasting, and/or infection. In some individuals, jaundice may only be
 apparent when triggered by one of these conditions. Some affected individuals have reported
 vague, unspecific symptoms including fatigue, weakness and gastrointestinal symptoms such as
 nausea, abdominal discomfort, and diarrhea.

 Gilbert syndrome is diagnosed more often in males than females. The disorder affects
 approximately 3-7 percent of individuals in the general population, and affects individuals
 of all races. It is present at birth, but may remain undiagnosed until the late teens or
 early twenties.

 Gilbert syndrome is caused by mutations to the UGT1A1 gene located on the long arm (q) of
 chromosome 2 (2q37). The UGT1A1 gene contains instructions for creating (encoding) a liver
 enzyme known as uridine disphosphate-glucuronosyltransferase-1A1 (UGT1A1). This enzyme is
 required for the conversion (conjugation) and subsequent excretion of bilirubin from the
 body. Individuals with Gilbert syndrome retain approximately one third of the normal UGT1A1
 enzyme activity and are able to conjugate enough bilirubin to prevent symptoms from
 developing.

 Mild jaundice associated with Gilbert syndrome occurs due to reduced amounts of this enzyme,
 which results in the accumulation of unconjugated bilirubin in the body. Bilirubin circulates
 in the liquid portion of the blood (plasma) bound to a protein called albumin; this is called
 unconjugated bilirubin, which does not dissolve in water (water-insoluble). Normally, this
 unconjugated bilirubin is taken up by the liver cells and, with the help of the UGT1A1
 enzyme, is converted to form water-soluble bilirubin glucuronides (conjugated bilirubin),
 which are then excreted in the bile. The bile is stored in the gall bladder and, when called
 upon, passes into the common bile duct and then into the upper portion of the small intestine
 (duodenum) and aids in digestion. Most bilirubin is eliminated from the body in the feces.

 New methods, like mass-spectrometry give a good chance to characterize specific metabolic
 alterations in the blood (plasma) of affected patients that allow diagnosing in the future
 the disease earlier, with a higher sensitivity and specificity.

 Therefore it is the goal of the study to identify and validate a new biochemical marker from
 the plasma of the affected patients helping to benefit other patients by an early diagnose
 and thereby with an earlier treatment.
INCLUSION CRITERIA

 -  Informed consent will be obtained from the patient or the parents before any study
 related procedures.

 -  Patients of both genders older than 2 months

 -  The patient has a diagnosis of Gilbert disease or a high-grade suspicion for Gilbert
 disease

 -  High-grade suspicion present, if one or more inclusion criteria are valid:

 1. - Positive family anamnesis for Gilbert disease

 2. - Hyperbilirubinemia

 3. - Abdominal pain

 4. - Irritable bowel syndrome

 5. - Familial nonhemolytic jaundice

 EXCLUSION CRITERIA

 -  No Informed consent from the patient or the parents before any study related
 procedures.

 -  Patients of both gender younger than 2 months

 -  No diagnosis of Gilbert disease or no valid criteria for profound suspicion of Gilbert
 disease