Despite the fact that both Wilson's disease and Indian childhood cirrhosis are characterized by hepatic dysfunction induced by copper exposure, their clinical and histological traits do not overlap.

Indian childhood cirrhosis may become symptomatic between the ages of 6 months and 5 years, more commonly after the child is one to two years old [1]. Disease onset is often gradual, with nonspecific signs such as malaise, irritability, sleeplessness, lack of appetite, constipation or diarrhea, fever and abdominal distension due to hepatosplenomegaly, representing pre-cirrhotic findings [2]. These abnormalities, including an enlarged liver, may have multiple causes in children, therefore an early diagnosis is difficult to establish. In severe cases, a hepatic bruit may be noticed. The ponderal curve becomes flat. Abdominal palpation reveals a hard liver with a sharp inferior border localized 3 to 5 centimeters under the inferior rib cage border. Splenomegaly appears after the liver has become enlarged. By the time jaundice appears, the liver function is severely compromised and events like hepatocellular failure, ascites, bleeding due to esophageal varices leading to anemia, bacterial infection and death occur rapidly. In the preterminal phase, symptoms of cirrhosis become overt and include confusion due to hepatic encephalopathy, palmar erythema, spider nevi localized on the upper torso, portal hypertension and hepatic coma. At this point, a specific garlic odor may also be present, also a sign of severe hepatic dysfunction. Dyspnea and cyanosis on exertion are probably a consequence of severe anemia.

Disease onset may also be sudden, with fever, clay-like stools, jaundice or coma. Cholestasis is generally a late trait of this illness.

• Fever

  Each had been well until progressive lethargy, abdominal swelling, jaundice, and fever developed four to seven months before death. [ncbi.nlm.nih.gov]

  Disease onset may also be sudden, with fever, clay-like stools, jaundice or coma. Cholestasis is generally a late trait of this illness. Blood workup should include standard hepatic function tests. [symptoma.com]

  Symposium on Liver Disorders Keywords Typhoid Fever Wilson Disease Strong Family History Hepatic Coma Typhoid Vaccine These keywords were added by machine and not by the authors. [doi.org]

• Anemia

  Dyspnea and cyanosis on exertion are probably a consequence of severe anemia. Disease onset may also be sudden, with fever, clay-like stools, jaundice or coma. Cholestasis is generally a late trait of this illness. [symptoma.com]

  Aminoacidemia reflecting renal tubular dysfunction and hemolytic anemia may also be found in both. [ncbi.nlm.nih.gov]

  In certain circumstances, the initial presentation may be that of acute liver failure accompanied by the sudden release of excess copper into the bloodstream with resultant hemolytic anemia. [medscape.com]

  Diagnosis suspected in infants or young children with painful swelling of the hands and feet, pallor, jaundice, pneumococcal sepsis or meningitis, severe anemia with splenic enlargement, or acute chest syndrome. [animals-partner.blogspot.com]

• Pathologist

  Pathology of Pediatric Gastrointestinal and Liver Disease will provide the pediatric pathologist, GI and general pathologist and pediatric gastroenterologist with the most current and complete reference on the pathology of pediatric GI and liver diseases [books.google.com]

  The alert clinician must be aware that such cases still exist and the pathologist has a key role to play in recognizing ICC and its variations. [ncbi.nlm.nih.gov]

  Because of the large influx of immigrants from the Indian subcontinent, Western pathologists should become more familiar with the true histologic and gross picture of ICC. [mdedge.com]

  Blinding (performance bias and detection bias) All outcomes Unclear risk Comments: It is mentioned only that the pathologists reviewed the biopsy specimens in a blinded manner. [onlinelibrary.wiley.com]

• Non-Alcoholic Cirrhosis

  Hepatology 9: 698–703 PubMed Google Scholar Bannister P, Oakes J, Sheridan P et al. (1987) Sex hormone changes in chronic liver disease: a matched study of alcoholic versus non-alcoholic liver disease. [link.springer.com]

• Easy Bruising

  Cirrhosis can lead to Easy bruising or bleeding, or nosebleeds Swelling of the abdomen or legs Extra sensitivity to medicines High blood pressure in the vein entering the liver Enlarged veins called varices in the esophagus and stomach. [medlineplus.gov]

• Nausea

  ˈi-lē-əs \ : obstruction of the bowel especially : functional obstruction of the gastrointestinal tract and especially the small intestine that is marked by the absence of peristalsis, is usually accompanied by abdominal pain, bloating, and sometimes nausea [merriam-webster.com]

  The symptoms of ileus are abdominal bloating caused by a buildup of gas and liquids, nausea, vomiting, severe constipation, loss of appetite, and cramps. People may pass watery stool. [merckmanuals.com]

  Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).People with cryptogenic cirrhosis may develop high blood [icdlist.com]

  […] conditions, such as IBD or diverticulitis electrolyte imbalance history of radiation near the abdomen intestinal injury losing weight very quickly peripheral artery disease sepsis Symptoms of ileus include: stomach cramps and pain bloated or swollen stomach nausea [medicalnewstoday.com]

  Lactose Intolerance Hypolactasia; persistent diarrhea; abdominal cramps; bloating; nausea; flatus Multiple endocrine neoplasia MEN2A (which affects 60% to 90% of MEN2 families):Medullary thyroid carcinoma; Pheochromocytoma (tumor of the adrenal glands [animals-partner.blogspot.com]

• Vomiting

  Severe vomiting is rare, but if it occurs, the buildup of gas and liquid caused by ileus must be relieved. [merckmanuals.com]

  […] obstruction of the bowel especially : functional obstruction of the gastrointestinal tract and especially the small intestine that is marked by the absence of peristalsis, is usually accompanied by abdominal pain, bloating, and sometimes nausea and vomiting [merriam-webster.com]

  Typically if this occurs one may vomit blood (which could be bright red or black like coffee grounds). Alternatively, blood might be noted in the stools – it could be bright red or black and tarry. This occurrence is a medical emergency. [chp.edu]

  Treatment at the hospital can include: intravenous fluids to prevent dehydration nasogastric decompression, which uses a tube to suction out materials that a person might otherwise vomit up pain relief Dietary changes Conditions such as Crohn’s disease [medicalnewstoday.com]

  Liver related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, yellowish skin, and itchiness. [howlingpixel.com]

• Loss of Appetite

  The symptoms of ileus are abdominal bloating caused by a buildup of gas and liquids, nausea, vomiting, severe constipation, loss of appetite, and cramps. People may pass watery stool. [merckmanuals.com]

  Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).People with cryptogenic cirrhosis may develop high blood [icdlist.com]

  […] of appetite feeling full inability to pass gas An ileus and an intestinal obstruction have similarities, but an ileus results from muscle or nerve problems that stop peristalsis while an obstruction is a physical blockage in the digestive tract. [medicalnewstoday.com]

  CLINICAL FEATURES • Discomfort in right upper quadrant due to mild hepatomegaly • Anorexia • Malaise • Weight loss • Loss of appetite • Jaundice • Ascites • Peripheral edema • Distended 32 Ramya Deepthi P 33. [slideshare.net]

• Diarrhea

  Disease onset is often gradual, with nonspecific signs such as malaise, irritability, sleeplessness, lack of appetite, constipation or diarrhea, fever and abdominal distension due to hepatosplenomegaly, representing pre-cirrhotic findings. [symptoma.com]

  anal fistulae and peri-rectal abscesses can also occur Cystic fibrosis Large amount of abnormally thick mucus in the lungs and intestines; leads to congestioni, pneumonia, diarrhea and poor growth Deafness (non-syndromic) Congenital loss of hearing; [animals-partner.blogspot.com]

  Forty patients (22%) gave history of recurrent fever, diarrhea or pneumonia in the past. Aerobic blood culture was done in 71 patients who initially presented with fever and had not received antibiotics. [tropicalgastro.com]

• Jaundice

  (2) An intermediate stage characterized by irritability, minimal jaundice, marked hepatomegaly, splenomegaly and occasionally, subcutaneous oedema, ascites and susceptibility to infection (3) A late stage with increasing jaundice, hepatosplenomegaly [histopathology.guru]

  Each had been well until progressive lethargy, abdominal swelling, jaundice, and fever developed four to seven months before death. [ncbi.nlm.nih.gov]

  Disease onset may also be sudden, with fever, clay-like stools, jaundice or coma. Cholestasis is generally a late trait of this illness. Blood workup should include standard hepatic function tests. [symptoma.com]

• Hepatomegaly

  On examination, he had hepatosplenomegaly with firm hepatomegaly and a leafy border. There were no other signs of liver cell failure. [pediatriconcall.com]

  […] recognized: (1) An early stage with an insidious onset characterized by disturbances of appetite and bowel movement, slight enlargement of the liver and occasional jaundice (2) An intermediate stage characterized by irritability, minimal jaundice, marked hepatomegaly [histopathology.guru]

  Among patients with liver cirrhosis, 63% had hepatomegaly, 44% had splenomegaly and 56% had dilated superficial veins with upward flow in abdomen and chest wall. [tropicalgastro.com]

  May be asymptomatic or complain of fatigue, pruritus, and non-jaundice skin hyperpigmentation with hepatomegaly. There is prominent alkaline phosphatase elevation as well as elevations in cholesterol and bilirubin. [gutenberg.us]

  CLINICAL FEATURES • Discomfort in right upper quadrant due to mild hepatomegaly • Anorexia • Malaise • Weight loss • Loss of appetite • Jaundice • Ascites • Peripheral edema • Distended 32 Ramya Deepthi P 33. [slideshare.net]

Blood workup should include standard hepatic function tests. Alanine transaminase and gamma glutamyl transpeptidase will be increased. A coagulation panel composed of bleeding and clotting time and prothrombin time should be obtained in order to further assess hepatic function and to prevent catastrophic bleeding following a liver biopsy. Ceruloplasmin and copper levels are within normal limits at first [3] [4]. Cupriuresis following d-penicillamine will be high.

Liver biopsy shows extensive hepatocyte damage, with liver cells appearing vacuolated, necrotic or ballooned. Histologic examination further describes the presence of inflammatory cells [5] and extensive pericellular intralobular fibrosis with poor regeneration, leading to a so- called "micro-micro nodular" cirrhosis [6] [7]. Hyaline inclusions, similar to those found in Wilson's disease or alcoholic liver disease have also been described. Fat deposits are small. However, there is one typical histological aspect of this disease, namely the presence of granules that color dark brown with orcein staining due to the fact that they consist of a copper-associated protein [8].

• Globulins Increased

  Globulins - increased due to shunting of bacterial antigens away from the liver to lymphoid tissue. Serum sodium - hyponatremia due to inability to excrete free water resulting from high levels of ADH and aldosterone. [gutenberg.us]

  Findings include elevations in serum globulins, especially gamma globulins. [15] Hereditary hemochromatosis. [en.wikipedia.org]

• Enlargement of the Spleen

  Other later symptoms, some due to complications, include: Reddened palms Loss of body hair Enlarged liver Enlarged spleen Appearance of thin, purplish-red, spidery looking blood vessels on the skin, especially around the navel Water retention and swelling [chp.edu]

  Other findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the liver fissures and enlargement of the spleen. [gutenberg.us]

  Other liver findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. [en.wikipedia.org]

• Liver Biopsy

  The liver biopsy eventually proved to be the most informative diagnostic test. [ncbi.nlm.nih.gov]

  Liver biopsy shows extensive hepatocyte damage, with liver cells appearing vacuolated, necrotic or ballooned. [symptoma.com]

The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1-9.3 years after commencing treatment. [ncbi.nlm.nih.gov]

The four children who still have micronodular cirrhosis beyond four years from onset remain on penicillamine treatment. [doi.org]

The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1–9.3 years after commencing treatment. [journals.lww.com]

Initially the boy was presented with:- Swelling in abdomen Fluid collection in abdomen Lack of appetite Developmental delay Elevated liver enzymes & AFP LINE OF TREATMENT I. [omicsonline.org]

"Indian childhood cirrhosis: clinical features, prognosis and treatment". Indian Journal of Pediatrics. 47 (389): 537–41. doi : 10.1007/BF02822546. PMID 7262970. Bavdekar, AR; Bhave, SA; Pradhan, AM; Pandit, AN; Tanner, MS (1996). [en.wikipedia.org]

Prognosis • Patients without jaundice, Ascites or heatemesis and are abstainers from alcohol have 90% five year survival. • Cause of death in alcoholic cirrhosis could be due to –  Hepatic coma  Massive gastrointestinal bleeding  Infections  Hepatocellular [slideshare.net]

This score uses bilirubin, albumin, INR, presence and severity of ascites and encephalopathy to classify patients in class A, B or C; class A has a favourable prognosis, while class C is at high risk of death. [gutenberg.us]

"Indian childhood cirrhosis: clinical features, prognosis and treatment". Indian journal of pediatrics. 47 (389): 537–41. doi : 10.1007/BF02822546. PMID 7262970. Bavdekar, AR; Bhave, SA; Pradhan, AM; Pandit, AN; Tanner, MS (1996). [howlingpixel.com]

These also constitute the indications for liver transplantation as they predict poor prognosis. In HVCS these symptoms occur before the development of cirrhosis or during early liver cirrhosis. [tropicalgastro.com]

This suggests that etiologies other than impaired MT production should be sought as the primary defect in these disorders. [ncbi.nlm.nih.gov]

The etiology of ICC remained unknown, although the role of a toxic injury to liver was hypothesized. [indianpediatrics.net]

CHILDHOOD CIRRHOSIS ICC is a chronic liver disease seen in pediatric age group and is unique to the Indian subcontinent First reported at kolkatta in 1880 as “infantile cirrhosis” or “infantile childhood cirrhosis” and was published in 1930 Definite etiologic [histopathology.guru]

Abstract Indian Childhood Cirrhosis (ICC) is a unique syndrome with characteristic clinical, epidemiological and histopathological features which is a major cause of mortality in India in children 1 to 4 years of age. [ncbi.nlm.nih.gov]

The latter can be explained by an epidemiological upward shift in age of presentation of ICC observed over a period of time [16]. [indianpediatrics.net]

Isolation of the NICC gene and defining its pathophysiology will significantly expand our insight into copper metabolism in man, which, at present, is largely limited. [ncbi.nlm.nih.gov]

Transplantation 27: 1760–1765 Google Scholar Roberts LR, Kamath PS (1996) Ascites and hepatorenal syndrome: pathophysiology and management. [link.springer.com]

"Hepatic encephalopathy: pathophysiology and emerging therapies". Med. Clin. North Am. 93 (4): 819–36, vii. doi : 10.1016/j.mcna.2009.03.009. PMID 19577116. ^ Ginés P, Arroyo V, Quintero E, et al. (1987). [en.wikipedia.org]

Pathophysiology The liver plays a vital role in synthesis of proteins (e.g., albumin, clotting factors and complement ), detoxification and storage (e.g., vitamin A ). In addition, it participates in the metabolism of lipids and carbohydrates. [gutenberg.us]

A common killer disease of the past, Indian childhood cirrhosis (ICC), which became preventable and treatable in the early 1990s, is now rare. [ncbi.nlm.nih.gov]

ABSTRACT A common killer disease of the past, Indian childhood cirrhosis (ICC), which became preventable and treatable in the early 1990s, is now rare. [doi.org]

It had a very high case fatality in the past [3] but has eventually become preventable, treatable and is now rare. [4] Variants [ edit ] North American Indian childhood cirrhosis [5] References [ edit ] Further reading [ edit ] North American Indian childhood [en.wikipedia.org]

1. Nayak N, Ramalingaswami V. Indian childhood cirrhosis. Clin Gastroenterol. 1975;4:333-349.
2. Parekh S, Patel B. Epidemiological survey of Indian childhood cirrhosis. Indian Pediatr. 1972;9:431-439.
3. Kapoor S, Singh M, Ghai OP. Study of serum copper oxidase in patients with Indian childhood cirrhosis. Indian J Med Res. 1971;59:115-121.
4. Vij S, Vij A. Serum magnesium, copper, and iron levels in infantile cirrhosis. Indian Pediatr. 1975;12:411-413.
5. Patel B, Parekh S, Chitale A. Histopathological evolution of Indian childhood cirrhosis with emphasis on criteria of early diagnoses. Indian Pediatr. 1974;11:19-28.
6. Tanner M, Portmann B, Mowat A, et al. Indian childhood cirrhosis presenting in Britain with orcein-positive deposits in liver and kidney. Br Med J. 1978;ii:928-929.
7. Nayak N, Ramalingaswami V. Indian childhood cirrhosis. Clin Gastroenterol. 1975;4:333-349.
8. Salaspuro M, Sipponen P. Demonstration of an intracellular copper-binding protein by orcein staining in long standing cholestatic liver diseases. Gut. 1976;17:787-790.