The enzymes that are defective in GS - UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) - are also responsible for some of the liver's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.

While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.

Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS.

Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis of data available up to 2002, and confirmed the incidence of atherosclerotic disease (hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognized as a potent antioxidant, rather than confounding factors such as high-density lipoprotein levels.

This association was also seen in long-term data from the Framingham Heart Study. Moderately elevated levels of bilirubin in people with GS and the (TA)/(TA) genotype were associated with one-third the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)/(TA) genotype (i.e. a normal, nonmutated gene locus).

Platelet counts and MPV are decreased in patients with Gilbert's Syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process.

One 10-year-old girl with Crigler–Najjar syndrome type I was successfully treated by liver cell transplantation.

The homozygous Gunn rat, which lacks the enzyme uridine diphosphate glucuronyltransferase (UDPGT), is an animal model for the study of Crigler–Najjar syndrome. Since only one enzyme is working improperly, gene therapy for Crigler-Najjar is a theoretical option which is being investigated.

It is caused due to deficient Glucuronidation of bilirubin, Glucuronidation increases the molecular weight of the drug which favours its excretion in bile.

Deficient Glucuronidation is caused by congenital deficiency of hepatic bilirubin glucuronosyltransferase(BGT)

Rotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder. It is a distinct, yet similar disorder to Dubin–Johnson syndrome — both diseases cause an increase in conjugated bilirubin.

Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal lifespans. Some neonates present with cholestasis. Hormonal contraceptives and pregnancy may lead to overt jaundice and icterus (yellowing of the eyes and skin).

Dubin–Johnson syndrome (DJS) is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.

Rotor syndrome has many features in common with Dubin–Johnson syndrome, an exception being that the liver cells are not pigmented. The main symptom is a non-itching jaundice. There is a rise in bilirubin in the patient's serum, mainly of the conjugated type.

It can be differentiated from Dubin–Johnson syndrome in the following ways:

It has been suggested that Rotor Syndrome may exacerbate toxic side effects of the drug irinotecan.

A defect in the UGT1A1-gene, also linked to Crigler–Najjar syndrome and Gilbert's syndrome, is responsible for the congenital form of Lucey–Driscoll syndrome.

Lucey–Driscoll syndrome is an autosomal recessive metabolic disorder affecting enzymes involved in bilirubin metabolism. It is one of several disorders classified as a transient familial neonatal unconjugated hyperbilirubinemia.

UGT1A1 gene mutations causes the condition. As a result, there can be reduced functionality of the bilirubin-UGT enzyme. Eventually it causes unconjugated hyperbilirubinemia and jaundice as substance accumulates in the body due to the reduced ability of the enzyme.

Hereditary hyperbilirubinemia refers to the condition where levels of bilirubin are elevated, for reasons that can be attributed to a metabolic disorder.

An example is Crigler-Najjar syndrome.

Congenital chloride diarrhea (CCD, also congenital chloridorrhea or Darrow Gamble syndrome) is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins. More than 20 mutations in the gene are known to date. A rare disease, CCD occurs in all parts of the world but is more common in some populations with genetic founder effects, most notably in Finland.

Characterised as a recessive disorder, symptomatic presentation requires the inheritance of aldolase A mutations from both parents. This conclusion is substantiated through the continuum type presentation witnessed, wherein heterozygous parents have intermediate enzyme activity. Structural instability has been indicated in four of the patients, with particular sensitivity to increased temperature according to direct enzymatic testing. This is exemplified in the early diagnosis of hereditary pyropoikilocytosis in the Sicilian girl. Deterioration with fever is likewise congruent. However, this direct relation has been disputed due to the increased overall metabolism and oxygen consumption also accompanying such maladies.

Sequence analysis has been conducted for three of the patients each revealing a distinct alteration at regions of typically high conservation. The conversion of the 128th aspartic acid to glycine causes conformational change according to CD spectral analysis and thermal lability in mutagenic analysis. Similarly the charge disruption created through the exchange of the negatively charged glutamic acid for positively charged lysine (at residue 209 of the E helix) disrupts interface interaction of the protein's subunits and therein destabilises its native tetrahedral configuration. The final case is unique in its non-homozygosity. A comparable maternal missense mutation wherein tyrosine is replaced by cysteine alters the carboxy-terminus due to its proximity to a crucial hinge structure. However, the paternal nonsense mutation at arginine 303 truncates the peptide. It is notable that Arg303 is required for enzymatic activity.

The initial 1973 case is atypical, in that no indication of aldolase A structural abnormality was found in isoelectric focusing, heat stabilization, electrophoresis or enzyme kinetics. It was concluded that either disordered regulation or a basic defect creating more rapid tetrameric inactivation were the most probable causes.

Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is "less than" 1 per 1,000,000), but there are at least 50 documented cases in the literature.

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry. According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.

Observations leading to the characterization of the SLC26 family were based on research on rare human diseases. Three rare recessive diseases in humans have been shown to be caused by genes of this family. Diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome are caused by the highly related genes SLC26A2 (first called DTDST), SLC26A3 (first called CLD or DRA), and SLC26A4 (first called PDS), respectively. Two of these diseases, diastrophic dysplasia and congenital chloride diarrhea, are Finnish heritage diseases.

Aldolase A deficiency, also called ALDOA deficiency, red cell aldolase deficiency or glycogen storage disease type 12 (GSD XII) is an autosomal recessive metabolic disorder resulting in a deficiency of the enzyme aldolase A; the enzyme is found predominantly in red blood cells and muscle tissue. The deficiency may lead to hemolytic anaemia as well as myopathy associated with exercise intolerance and rhabdomyolysis in some cases.

Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

Emanuel Syndrome can be diagnosed with a karyotype, with FISH, or with a chromosomal microarray analysis. .

Type 1 tyrosinemia, also known as hepatorenal tyrosinemia or tyrosinosis, is the most severe form of tyrosinemia, a buildup of too much of the amino acid tyrosine in the blood and tissues due to an inability to metabolize it. It is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase.

Emanuel Syndrome does not have a cure, but individual symptoms may be treated. Assessments of individual systems, such as the cardiovascular, gastrointestinal, orthopedic, and neurological may be necessary to determine the extent of impairment and options for treatment.

"Breastfeeding jaundice" or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.

Hereditary coproporphyria (HCP) is a disorder of heme biosynthesis, classified as an acute hepatic porphyria. HCP is caused by a deficiency of the enzyme coproporphyrinogen oxidase, coded for by the "CPOX" gene, and is inherited in an autosomal dominant fashion, although homozygous individuals have been identified. Unlike acute intermittent porphyria, individuals with HCP can present with cutaneous findings similar to those found in porphyria cutanea tarda in addition to the acute attacks of abdominal pain, vomiting and neurological dysfunction characteristic of acute porphyrias. Like other porphyrias, attacks of HCP can be induced by certain drugs, environmental stressors or diet changes. Biochemical and molecular testing can be used to narrow down the diagnosis of a porphyria and identify the specific genetic defect. Overall, porphyrias are rare diseases. The combined incidence for all forms of the disease has been estimated at 1:20,000. The exact incidence of HCP is difficult to determine, due to its reduced penetrance.

MCAS is a relatively new diagnosis, being unnamed until 2007, and is believed to be very under-diagnosed. New findings are revealing that MCAS is much more prevalent than previously thought.