Jaundice, also known as icterus (attributive adjective: “icteric”), is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids. Typically, the concentration of bilirubin in the plasma must exceed 1.5 mg/dL[1], three times the usual value of approximately 0.5mg/dL[1], for the coloration to be easily visible. Jaundice comes from the French word jaune, meaning yellow.

One of the first tissues to change color as bilirubin levels rise in jaundice is the conjunctiva of the eye, a condition sometimes referred to as scleral icterus. However, the sclera themselves are not “icteric” (stained with bile pigment) but rather the conjunctival membranes that overlie them. The yellowing of the “white of the eye” is thus more properly conjunctival icterus.[2] See photographic illustration at right.

In order to understand how jaundice results, the pathological processes that cause jaundice to take their effect must be understood. Jaundice itself is not a disease, but rather a sign of one of many possible underlying pathological processes that occurs at some point along the normal physiological pathway of the metabolism of bilirubin.

When red blood cells have completed their life span of approximately 120 days, or when they are damaged, their membranes become fragile and prone to rupture. As each red blood cell traverses through the reticuloendothelial system, its cell membrane ruptures when its membrane is fragile enough to allow this. Cellular contents, including hemoglobin, are subsequently released into the blood. The hemoglobin is phagocytosed by macrophages, and split into its heme and globin portions. The globin portion, being protein, is degraded into amino acids and plays no further role in jaundice. Two reactions then take place with the heme molecule. The first oxidation reaction is catalyzed by the microsomal enzyme heme oxygenase and results in biliverdin (green color pigment), iron and carbon monoxide. The next step is the reduction of biliverdin to a yellow color tetrapyrol pigment called bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is “unconjugated”, “free” or “indirect” bilirubin. Approximately 4 mg per kg of bilirubin is produced each day.[3] The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 per cent comes from other heme sources, including ineffective erythropoiesis, breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes.[3]

The unconjugated bilirubin then travels to the liver through the bloodstream. Because this bilirubin is not soluble, however, it is transported through the blood bound to serum albumin. Once it arrives at the liver, it is conjugated with glucuronic acid (to form bilirubin diglucuronide, or just “conjugated bilirubin”) to become more water soluble. The reaction is catalyzed by the enzyme UDP-glucuronide transferase.

This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Intestinal bacteria convert the bilirubin into urobilinogen. From here the urobilinogen can take two pathways. It can either be further converted into stercobilinogen, which is then oxidized to stercobilin and passed out in the faeces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine as the oxidised product urobilin. Stercobilin and urobilin are the products responsible for the coloration of faeces and urine, respectively.

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Jarcho-Levin Syndrome is a rare, heritable axial skeleton growth disorder. It is characterized by widespread and sometimes severe malformations of the vertebral column and ribs, shortened thorax, and moderate to severe scoliosis and kyphosis. Individuals with Jarcho-Levin typically appear to have a short trunk and neck, with arms appearing relatively long in comparison, and a slightly protuberant abdomen. Severely affected individuals may have life-threatening pulmonary complications due to deformities of the thorax. The syndrome was first described by Saul Jarcho and Paul M. Levin at Johns Hopkins University in 1938. [1]

While clinicians almost unanimously refer to the syndrome as “Jarcho-Levin”, reports have variously labelled or referred to the condition as all of the following: Hereditary malformations of the vertebral bodies,[1] hereditary multiple hemivertebrae,[2] syndrome of bizarre vertebral anomalies,[3] spondylocostal dysplasia,[4] spondylothoracic dysplasia,[5] costovertebral anomalies,[6] costovertebral dysplasia,[7] spondylothoracic dysplasia,[8] occipito-facial-cervico-thoracic-abdomino-digital dysplasia[9] (deemed “ridiculously long” and “unwarranted” by OMIM)[1], and spondylocostal dysostosis.[10]

A closely related condition termed “Costovertebral segmentation defect with mesomelia and peculiar facies”, or Covesdem syndrome, was first described in 1978 in India. [11]

Babies born with Jarcho-Levin may be very healthy and grow up to lead normal lives.[12] However, many individuals with Jarcho-Levin suffer from problems of respiratory insufficiency secondary to volume-restricted thoraces. These individuals will often develop pulmonary complications and die in infancy or early childhood.[1][2][13][14][15] The disparity in outcomes of those with the syndrome is related to the fact that Jarcho-Levin actually encompasses two or more distinct syndromes, each with its own range of prognoses. The syndromes currently recognized as subtypes of Jarcho-Levin are termed Spondylothoracic Dysplasia and Spondylocostal Dysostosis.

In 1968, Dr. David Rimoin and colleagues in Baltimore first distinguished between the two major presentations of Jarcho-Levin.[4] Both conditions were characterized as failures of proper vertebral segmentation. However, the condition within the family described in their article appeared to be inherited in a autosomal dominant fashion and had a less severe course than that reported by other investigators. They specified their condition as spondylocostal dysplasia, which has since become to be known as Spondylocostal Dysostosis. The subtype of Jarcho-Levin with which they contrasted their reported cases to is now known as Spondylothoracic Dysplasia.

Spondylothoracic dysplasia, or STD, has been repeatedly described as an autosomal recessively inherited condition that results in a characteristic fan-like configuration of the ribs with minimal intrinsic rib anomalies. Infants born with this condition typically died early in life due to recurrent respiratory infections and pneumonia due to their restricted thorax.[3][5][16] Recently, a report[12] has documented that actual mortality associated with STD is only about 50%, with many survivors leading healthy, independent lives.

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Jackson-Weiss syndrome (JWS) is a genetic disorder characterized by foot abnormalities and the premature fusion of certain bones of the skull (craniosynostosis), which prevents further growth of the skull and affects the shape of the head and face.

Many of the characteristic facial features of Jackson-Weiss syndrome result from the premature fusion of the skull bones and foot bones. The head is unable to grow normally, which can lead to a misshapen skull, widely spaced eyes, and a bulging forehead. Foot abnormalities are the most consistent characteristic, as not all individuals with Jackson-Weiss syndrome have abnormal skull or facial features. The big toes are enlarged and bend away from the other toes. Hand abnormalities are rare. People with Jackson-Weiss syndrome usually have normal intelligence and a normal life Span.

Jackson-Weiss syndrome is a rare genetic disorder; its incidence is unknown.

Mutations in the FGFR2 gene cause Jackson-Weiss syndrome. The FGFR2 gene produces a protein called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become bone cells in a developing embryo and fetus. A mutation in a specific part of the FGFR2 gene alters the protein and causes prolonged signaling, which promotes the premature fusion of bones in the skull and feet.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

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Jacobsen Syndrome, also known as 11q deletion, is a rare congenital disorder resulting from deletion of a terminal region of chromosome 11 that includes band 11q24.1. It can cause intellectual disabilities, a distinctive facial appearance, and a variety of physical problems including heart defects and a bleeding disorder. The syndrome was first identified by Danish physician Petra Jacobsen in 1973,[1] and is believed to occur in approximately 1 out of every 100,000 births.

In addition, patients tend to be shorter than average and have poor psychomotor skills.

Patients with this disorder can often live relatively normal lives within the limitations of their disability, although this varies from person to person, and congenital heart disease that does not manifest itself until adulthood is common. There is a greater incidence of various forms of cancer among Jacobsen patients. The vast majority of patients have a bleeding disorder called Paris-Trousseau Syndrome, which causes reduced blood platelet counts and an impairment of platelets’ normal blood clotting function. Platelet counts increase during childhood and can eventually reach normal levels, but many patients still have poor clotting due to abnormalities in platelet function. Unless their platelet function has been tested and shown to be normal, Jacobsen patients should be assumed to have a bleeding disorder.

The majority of Jacobsen syndrome cases are not familial in nature, resulting from a spontaneous mutation occurring in a single parental gamete. However, some instances of familial disease resulting from local chromosome fragility or an unbalanced translocation have been described.

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Jansky-Bielschowsky disease is a late-infantile form of neuronal ceroid lipofuscinosis associated with a deficiency in tripeptidyl peptidase I.[1]

It is named for Jan Janský and Max Bielschowsky.[2]

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Japanese encephalitis (Japanese: ????, Nihon-noen; previously known as Japanese B encephalitis to distinguish it from von Economo’s A encephalitis) is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. One of the most important vectors of this disease is the mosquito Culex tritaeniorhynchus. This disease is most prevalent in Southeast Asia and the Far East.

Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Rare outbreaks in U.S. territories in Western Pacific have occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, Korea, Japan, Taiwan and Thailand. Other countries that still have periodic epidemics include Vietnam, Cambodia, Myanmar, India, Nepal, and Malaysia. Japanese encephalitis has been reported on the Torres Strait Islands and two fatal cases were reported in mainland northern Australia in 1998. The spread of the virus in Australia is of particular concern to Australian health officials due to the unplanned introduction of Culex gelidus, a potential vector of the virus, from Asia. However, the current presence on mainland Australia is minimal. Human, cattle and horses are dead-end hosts and disease manifests as fatal encephalitis. Swine acts as amplifying host and has very important role in epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. Infection in Humans occur in the ear, particularly the cochlea. The most important vector is C. tritaeniorhynchus, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation can divert the mosquito away from humans and swine The natural host of the Japanese encephalitis virus is bird, not human, and many believe the virus will therefore never be completely eliminated.

Japanese encephalitis has an incubation period of 5 to 15 days and the vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis.

Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Transplacental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had central nervous system involvement. In known cases some effects also include, nausea, headache, fever, vomiting and sometimes swelling of the testicles.

The causative agent Japanese encephalitis virus is an enveloped virus of the genus flavivirus; it is closely related to the West Nile virus and St. Louis encephalitis virus. Positive sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER)[1][2] and rapidly accumulates substantial amounts of viral proteins for the JEV.

Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISA.[3]

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Jervell and Lange-Nielsen syndrome, a type of long QT syndrome, causes the cardiac muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats, called arrhythmias, can lead to fainting, seizures, or sudden death. The disorder also contributes to hearing loss.

This condition is an autosomal recessive disorder that affects an estimated 1.6 to 6 in 1 million children, and is responsible for less than 10 percent of all cases of long QT syndrome.

Mutations in the KCNE1 and KCNQ1 genes cause Jervell and Lange-Nielsen syndrome. The proteins produced by these two genes work together to form a potassium channel that transports positively charged potassium ions out of cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of the inner ear and cardiac muscle.

About 90 percent of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in the KCNQ1 gene. KCNE1 mutations are responsible for the remaining 10 percent of cases. Mutations in these genes alter the usual structure and function of potassium channels or prevent the assembly of normal channels. These changes disrupt the flow of potassium ions in the inner ear and in cardiac muscle, leading to the hearing loss and irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.

This article incorporates public domain text from The U.S. National Library of Medicine

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Aphalangy, hemivertebrae and urogenital-intestinal dysgenesis is an extremely rare syndrome, described only in three siblings[1]. It associates hypoplasia or aplasia of phalanges of hands and feet, hemivertebrae and various urogenital and/or intestinal abnormalities. Intrafamilial variability is important as one sister had lethal abnormalities (Potter syndrome and pulmonary hypoplasia), while her affected brother was in good health with normal psychomotor development at 6 months of age. Prognosis seems to depend mainly on the severity of visceral malformations. Etiology and inheritance remain unknown.[2][3]

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Joubert syndrome is a rare genetic disorder that affects the area of the brain that controls balance and coordination.

The disorder is characterized by absence or underdevelopment of a part of the brain called the cerebellar vermis and a malformed brain stem (molar tooth sign). The most common features include ataxia (lack of muscle control), an abnormal breathing pattern called hyperpnea, sleep apnea, abnormal eye and tongue movements, and hypotonia. Other malformations such as extra fingers and toes, cleft lip or palate, tongue abnormalities, and seizures may also occur. There may be mild or moderate retardation. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa . [1] The syndrome was first identified by pioneering pediatric neurologist Dr. Marie Joubert in Montreal Canada, while working at the Montreal Neurological Institute and McGill University.[2]

Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, and speech therapy may benefit some patients. Infants with abnormal breathing patterns should be monitored.

The prognosis for individuals with Joubert syndrome varies. Some patients have a mild form with minimal motor disability and good mental development, while others may have severe motor disability and moderate mental retardation.

Multiple genes that are mutated in individuals with Joubert syndrome have been identified:

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Jumping Frenchmen of Maine is a rare disorder originally described by George Miller Beard in 1878.[1][2]

It results in an exaggerated “startle” reflex,[3] and was first noted among related French-Canadian lumberjacks in the Moosehead Lake area of Maine. It is not clear if the disorder is neurological or psychological.

The “Jumping Frenchmen” seemed to react abnormally to sudden stimuli. Beard recorded, for instance, individuals who would obey any command given suddenly, even if it meant striking a loved one, and repeat back unfamiliar or foreign phrases uncontrollably. Beard also noticed that the condition was often shared within a family, suggesting that it was inherited.

The interest sparked by Beard’s publication about the disorder inspired Georges Gilles de la Tourette to investigate what later became known as Tourette’s syndrome. Further studies of the condition in the 1980s, however, cast doubt on whether the “Jumping Frenchmen” phenomenon was in fact a physical condition like Tourette’s. Documentation of direct observation of “Jumping Frenchmen” has been scarce, and while videotape evidence was recorded by several researchers that showed the condition to be real, Saint-Hilaire concluded from studying eight affected people that it was brought on by conditions at their lumber camps and was psychological, not neurological.[4]

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