The primary malformation apparent with JBS is hypoplasia (underdevelopment) of the nasal alae, or "wing of the nose". Both hypoplasia and aplasia (partial or complete absence) of structural cartilage and tissue in this area of the nose, along with the underlying alae nasi muscle, are prevailing features of the disorder. Together, these malformations give the nose and nostrils an odd shape and appearance.

Endocrine insufficiency of the pancreas occurs with JBS, though it is sometimes less common and less pronounced than the more prominent effects on exocrine function. The islets of Langerhans are ducts in the pancreas where endocrine activity such as the release of hormones glucagon, somatostatin and insulin takes place. Pancreatic endocrine insufficiency in JBS can be associated with either a buildup of connective tissue in the islet regions, congenital replacement of the islets with fatty tissue, or improper nerve signalling to the islets. Endocrine dysfunction of the pancreas often results in diabetes mellitus. Both insulin resistance and diabetes have been observed with JBS, and it is suggested that diabetes should be considered as a complication of JBS and its course.

Ductular output of fluids and electrolytes is preserved in the pancreas of many with JBS, as well as moderate to normal levels of functioning bicarbonate.

Endocrine abnormalities in other areas have also been present with the disorder. These include hypothyroidism, growth hormone deficiency and hypopituitarism. Findings affecting pituitary function in some JBS patients have included such anomalies as the formation of a glial hamartoma (a neoplasm, or tumor composed of glial cells) on a lobe of the pituitary gland, as well congenital underdevelopment of the anterior pituitary. Growth failure and associated short stature (dwarfism) in JBS can be attributed to growth hormone deficiency caused by diminished anterior pituitary function, with malabsorption of fats playing a subsequent role.

Initially, the symptoms of biliary atresia are indistinguishable from those of neonatal jaundice, a usually harmless condition commonly seen in infants. Distinctive symptoms of biliary atresia are usually evident between one and six weeks after birth. Infants and children with biliary atresia develop progressive cholestasis, a condition in which bile is unable to leave the liver and builds up inside of it. When the liver is unable to excrete bilirubin through the bile ducts in the form of bile, bilirubin begins to accumulate in the blood, causing symptoms. These symptoms include yellowing of the skin, itchiness, poor absorption of nutrients (causing delays in growth), pale stools, dark urine, and a swollen abdomen. Eventually, cirrhosis with portal hypertension will develop. If left untreated, biliary atresia can lead to liver failure. Unlike other forms of jaundice, however, biliary-atresia-related cholestasis mostly does not result in kernicterus, a form of brain damage resulting from liver dysfunction. This is because in biliary atresia, the liver, although diseased, is still able to conjugate bilirubin, and conjugated bilirubin is unable to cross the blood–brain barrier.

Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itching (pruritus), pale stools (acholia), an enlarged liver (hepatomegaly), an enlarged spleen (splenomegaly) and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity) or, in some cases, the complete absence of bile ducts (biliary atresia). Bile duct paucity results in the reduced absorption of fat and vitamins (A, D, E and K), which may lead to rickets or a failure to thrive in children. Around 15% of patients will experience liver cirrhosis in the course of their disease. Hepatocellular cancer has been reported in a number of cases.

The severity of the disorder can vary within the same family, with symptoms ranging from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation. It is difficult to predict a given patient's prognosis, but there are a few known indicators of earlier death.

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.

The onset of the disease is usually before age 2, but patients have been diagnosed with PFIC even into adolescence. Of the three entities, PFIC-3 usually presents earliest. Patients usually present in early childhood with cholestasis, jaundice, and failure to thrive. Intense pruritus is characteristic; in patients who present in adolescence, it has been linked with suicide. Patients may have fat malabsorption, leading to fat soluble vitamin deficiency, and complications, including osteopenia.

Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the liver in which one or more bile ducts are abnormally narrow, blocked, or absent. It can be congenital or acquired. As a birth defect in newborn infants, it has an incidence of one in 10,000–15,000 live births in the United States, and a prevalence of one in 16,700 in the British Isles. Biliary atresia is most common in East Asia, with a frequency of one in 5,000.

The causes of biliary atresia are not well understood. Congenital biliary atresia has been associated with certain genes, while acquired biliary atresia is thought to be a result of an autoimmune inflammatory response, possibly due to a viral infection of the liver soon after birth. The only effective treatments are surgeries such as the Kasai procedure and liver transplantation.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.

SLOS can present itself differently in different cases, depending on the severity of the mutation and other factors. Originally, SLOS patients were classified into two categories (classic and severe) based on external behaviours, physical characteristics, and other clinical features. Since the discovery of the specific biochemical defect responsible for SLOS, patients are given a severity score based on their levels of cerebral, ocular, oral, and genital defects. It is then used to classify patients as having mild, classical, or severe SLOS.

The most common facial features of SLOS include microcephaly, bitemporal narrowing (reduced distance between temples), ptosis, a short and upturned nose, micrognathia, epicanthal folds, and capillary hemangioma of the nose. Other physical characteristics include:

- low-set and posteriorly rotated ears

- high-arched, narrow, hard palate

- cleft lip/palate

- agenesis or hypoplasia of the corpus callosum

- cerebellar hypoplasia

- increased ventricular size

- decreased frontal lobe size

- polydactyly of hands or feet

- short, proximally placed thumb

- other finger malformations

- syndactyly of second and third toes

- ambiguous or female-like male genitalia

- congenital heart defects

- renal, pulmonary, liver and eye abnormalities

Hypertryptophanemia, also called familial hypertryptophanemia, is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria ("-uria" denotes "in the urine").

Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport. However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.

Mirizzi's syndrome has no consistent or unique clinical features that distinguish it from other more common forms of obstructive jaundice. Symptoms of recurrent cholangitis, jaundice, right upper quadrant pain, and elevated bilirubin and alkaline phosphatase may or may not be present. Acute presentations of the syndrome include symptoms consistent with cholecystitis.

Surgery is extremely difficult as Calot's triangle is often completely obliterated and the risks of causing injury to the CBD are high.

Dubin–Johnson syndrome is similar to Rotor syndrome, but can be differentiated by:

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

Neonatal jaundice may develop in the presence of sepsis, hypoxia, hypoglycemia, hypothyroidism, hypertrophic pyloric stenosis, galactosemia, fructosemia, etc.

Hyperbilirubinemia of the unconjugated type may be caused by:

- increased production

- hemolysis (e.g., hemolytic disease of the newborn, hereditary spherocytosis, sickle cell disease)

- ineffective erythropoiesis

- massive tissue necrosis or large hematomas

- decreased clearance

- drug-induced

- physiological neonatal jaundice and prematurity

- liver diseases such as advanced hepatitis or cirrhosis

- breast milk jaundice and Lucey–Driscoll syndrome

- Crigler–Najjar syndrome and Gilbert syndrome

In Crigler–Najjar syndrome and Gilbert syndrome, routine liver function tests are normal, and hepatic histology usually is normal, too. No evidence for hemolysis is seen. Drug-induced cases typically regress after discontinuation of the substance. Physiological neonatal jaundice may peak at 85–170 µmol/l and decline to normal adult concentrations within two weeks. Prematurity results in higher levels.

Bile acid malabsorption, known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy and bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

A number of abnormalities and symptoms have been observed with hypertryptophanemia.

Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).

Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings), hyperaggressive behavior; hypertelorism (widely-set eyes),

optical strabismus (misalignment) and myopia.

Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25-73 micromole/l) in some instances.

A product of the bacterial biosynthesis of tryptophan is indole. The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.

Type II differs from type I in several aspects:

- Bilirubin levels are generally below 345 µmol/L [20 mg/dL] (range 100–430 µmol/L [6–24 mg/dL]; thus, overlap occurs), and some cases are only detected later in life.

- Because of lower serum bilirubin, kernicterus is rare in type II.

- Bile is pigmented, instead of pale in type I or dark as normal, and monoconjugates constitute the largest fraction of bile conjugates.

- UGT1A1 is present at reduced but detectable levels (typically <10% of normal), because of single base pair mutations.

- Therefore, treatment with phenobarbital is effective, generally with a decrease of at least 25% in serum bilirubin. In fact, this can be used, along with these other factors, to differentiate type I and II.

- The inheritance pattern of Crigler–Najjar syndrome type II has been difficult to determine, but is generally considered to be autosomal recessive.

Congenital disorder of glycosylation type IIc or Leukocyte adhesion deficiency-2 (LAD2) is a type of leukocyte adhesion deficiency attributable to the absence of neutrophil sialyl-LewisX, a ligand of P- and E-selectin on vascular endothelium. It is associated with "SLC35C1".

This disorder was discovered in two unrelated Israeli boys 3 and 5 years of age, each the offspring of consanguineous parents. Both had severe mental retardation, short stature, a distinctive facial appearance, and the Bombay (hh) blood phenotype, and both were secretor- and Lewis-negative. They both had had recurrent severe bacterial infections similar to those seen in patients with LAD1, including pneumonia, peridontitis, otitis media, and localized cellulitis. Similar to that in patients with LAD1, their infections were accompanied by pronounced leukocytosis (30,000 to 150,000/mm) but an absence of pus formation at sites of recurrent cellulitis. In vitro studies revealed a pronounced defect in neutrophil motility. Because the genes for the red blood cell H antigen and for the secretor status encode for distinct α1,2-fucosyltransferases and the synthesis of Sialyl-LewisX requires an α1,3-fucosyltransferase, it was postulated that a general defect in fucose metabolism is the basis for this disorder. It was subsequently found that GDP-L-fucose transport into Golgi vesicles was specifically impaired, and then missense mutations in the GDP-fucose transporter cDNA of three patients with LAD2 were discovered. Thus, GDP-fucose transporter deficiency is a cause of LAD2.

Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.

Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development. In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions, and in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.

Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts. Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.

Postcholecystectomy syndrome describes the presence of abdominal symptoms after surgical removal of the gallbladder (cholecystectomy), 2 years after the surgery.

Symptoms of postcholecystectomy syndrome may include:

- Dyspepsia, nausea, and vomiting.

- Flatulence, bloating, and diarrhea.

- Persistent pain in the upper right abdomen.

Symptoms occur in about 5 to 40 percent of patients who undergo cholecystectomy, and can be transient, persistent or lifelong. The chronic condition is diagnosed in approximately 10% of postcholecystectomy cases.

The pain associated with postcholecystectomy syndrome is usually ascribed to either sphincter of Oddi dysfunction or to post-surgical adhesions. A recent study shows that postcholecystectomy syndrome can be caused by biliary microlithiasis.

Approximately 50% of cases are due to biliary causes such as remaining stone, biliary injury, dysmotility, and choledococyst. The remaining 50% are due to non-biliary causes. This is because upper abdominal pain and gallstones are both common but are not always related.

Chronic diarrhea in postcholecystectomy syndrome is a type of bile acid diarrhea (type 3). This can be treated with a bile acid sequestrant like cholestyramine, colestipol or colesevelam, which may be better tolerated.

Mirizzi's syndrome is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in obstruction and jaundice. The obstructive jaundice can be caused by direct extrinsic compression by the stone or from fibrosis caused by chronic cholecystitis (inflammation). A cholecystocholedochal fistula can occur.