Comparison of Serum Zinc in Children of Wilson Disease and Non-Wilsonian Volunteers in Bangladesh.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism with diverse clinical manifestations. Zinc (Zn) has been used for treatment of WD. Recent studies showed low serum zinc level in patients suffering from WD than the normal. This cross-sectional analytical study has been designed to compare the serum zinc level between paediatric patients suffering from WD but yet not started treatment and children who have normal ALT level. This study was carried out at the Department of Pediatric Gastroenterology and Nutrition, BSMMU, Dhaka, Bangladesh from July 2018 to June 2019. Total 51 children were included in this study. Among them 27 were diagnosed case of WD aged between three to eighteen years and 24 children of same ages who were suffering from other than liver disease having normal ALT were included as volunteers. The patients of WD were divided into four groups according to their presentation as acute hepatitis, chronic liver disease (CLD), acute liver failure & neuropsychiatric manifestation. Informed written consent was obtained from all patients and volunteers for participation in this study. Along with other physical findings and laboratory investigations 3 ml of venous blood were collected for estimation of serum zinc level. After estimation of serum zinc level results were analyzed statistically. The difference in serum zinc levels were compared between the groups. Serum zinc level was significantly lower in Wilson disease patients (43.8±19.7µg/dl; range: 13-83) compared to volunteers group (67.8±11.8µg/dl; range: 47-97) p<0.001. Among the diseased group, serum zinc level were significantly lower in 18 CLD (38.4±17.4µg/dl) and in 4 acute liver failure (33.1±3.7µg/dl) compared to 4 acute hepatitis (71.8±4.3µg/dl) (p=0.001) and (p<0.001) respectively. Mean serum zinc level was low in 4 Wilsonian acute liver failure (33.1±3.7µg/dl), which was significant compared to those (23) who presented as Wilson disease non acute liver failure (45.7±20.8µg/dl) (p=0.013). Serum zinc level was significantly lower in Wilson disease children compared to the volunteers. Zinc level was also found significantly low in Wilson disease presented as CLD and acute liver failure in comparison to Wilson disease presented as acute hepatitis.

COVID 19 in Children: Gastrointestinal, Hepatobiliary and Pancreatic Manifestation.

The most devastating pandemic of this era coronavirus disease-2019 (COVID-19) is caused by a novel virus named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Although it is primarily a respiratory pathogen, it can also result in several extra-pulmonary manifestations includes gastrointestinal symptoms, hepatocellular injury. Angiotensin-converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2), the entry receptor for the causative coronavirus SARS-CoV-2 is co-express in the gastrointestinal tract, hepatocyte, and cholangiocytes similar to the respiratory mucosa. The presence of these receptors facilitates the entry into the tissue and causes direct viral tissue damage, which is a proposed mechanism of injury. Diarrhoea, nausea, vomiting, abdominal discomfort are common gastrointestinal manifestations, whereas derangement of liver function tests is the most hepatic manifestation in COVID-19. In this article, we reviewed on SARS-CoV-2 disease COVID-19 regarding gastrointestinal, hepatic, and pancreatic manifestation, the mechanisms by which the virus may inflict damage, and their management perspective.

Irritable Bowel Syndrome: Is it Rare in Children?

Irritable bowel syndrome (IBS) is one of the most common and best studied disorders among the group of functional gastrointestinal disorders. It is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit. Visceral hypersensitivity and increased GIT motility are the main patho-physiological mechanism for developing IBS. IBS present with diarrhea and constipation or both. Investigation is least needed for diagnosis of IBS rather done to exclude differential diagnosis. Diagnosis is done on the basis of Rome-III criteria. Proper counseling, dietary management, anti-spasmotic and antidepressant are the mainstay of treatment.

Childhood Wilson Disease: Bangladesh Perspective.

Wilson's disease (WD) is an autosomal recessive disorder affecting copper metabolism causing copper induced damage to various organs. In children liver is commonly involved. Central nervous system, eyes, RBC, kidneys, brain and bones may also be affected. Aim of the study is to evaluate clinical & laboratory profile of Wilson's disease in children. This cross sectional descriptive study was conducted at the department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2011 to December, 2013. One hundred consecutive children of WD between 3 to 18 years of age were evaluated for clinical & biochemical profile. Mean age of studied children was 8.5±1.5 years. Male female ratio was 2:1. Ninety one percent patients were Muslim and nine percent Hindu. Consanguinity of marriage was found in 30% cases. Seven parents were first degree cousin. Family history of chronic liver disease was present in 15% of patients. Most (53%) cases of the hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Among 100 patients of WD, 69 children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic & neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of chronic liver disease were found in 18% patients. Commonest stigmata was thenar and hypothenar wasting (n=8). Keiser- Fleischser ring (K-F ring) was found in 76% of the total patients. K-F ring was present in 84% ( 58 out of 69) of the hepatic only Wilsonian patients and in 90% (18 out of 20) of all neurologic Wilsonian patients. Asymptomatic and psychiatric patient had no K-F ring. About 26% of the WD patients had Coombs negative hemolytic anemia in PBF. Most of the WD patients had altered liver function. Elevated serum transaminase was found in 85% of all cases, prolonged prothrombin time in 59% cases & low serum albumin in 53% cases. Seventy three percent patients had low serum ceruloplasmin, basal urinary copper of >100µgm/day was found in 81% cases and urinary copper following penicillamine challenge of >1200µgm/day was found in 92% cases. In 28 cases with hepatic presentation esophageal varices were identified by upper gastrointestinal endoscopy. WD patient with hepatic presentations were given zinc sulphate along with penicillamine. All patients with neurological manifestation as well as asymptomatic cases were maintained on zinc therapy. WD is a treatable metabolic cause of liver disease. Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.

Aetiology and Outcome of Acute Liver Failure in Children: Experience at a Tertiary Care Hospital of Bangladesh.

Acute liver failure (ALF) is a rapidly progressive, potentially fatal syndrome resulting from rapid death or injury to a large proportion of hepatocytes, caused by a variety of insult, leaving insufficient hepatic paranchymal mass to sustain liver function. The aetiology of ALF varies according to the age of patient and development of the country. The outcome of ALF also varies according to aetiology: survival is better in paracetamol poisoning whereas it is poor in metabolic diseases. The present study was undertaken to observe the underlying aetiology and outcome of ALF in children under 18 years of age admitted at the department of Paediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. It was a retrospective review of medical records from November 2011 through October 2014. During this period a total of 35 patients were diagnosed to have ALF. Aetiology was established in 25(71.4%) cases, whereas in 10(28.6%) cases, no identifiable cause was found. Viral hepatitis was the underlying cause in 12(34.3%) cases. After treatment 15(43%) ALF patients survived, 8(23%) left hospital with risk bond (DORB), and 12(34%) patients died. The study showed that among the 12 death patients, 5(41.7%) had viral hepatitis, 3(25%) Wilson's disease, and in 4(33.3%) no cause could be identified. Viral hepatitis and Wilson disease were found to be two common causes of ALF in this study. Future studies with larger sample size are required to know the actual causes of acute liver failure in Bangladeshi children.

Penicillamine challenge test in the diagnosis of Wilson's disease.

Wilson's disease (WD) is one of the most common metabolic liver diseases encountered in children. Early diagnosis of the disease is essential because specific treatment can be offered, that will prevent further hepatocellular injury and neurologic complications. There is no single diagnostic test that can exclude or confirm the disease with certainty. Penicillamine challenge has proved itself to be a useful diagnostic test in the detection of WD. The main purpose of this study was to observe the reliability of penicillamine challenge test, in the diagnosis of WD. The cross sectional study was done with a case control design in the department of paediatric gastroenterology & Nutrition, BSMMU, Dhaka. The study was carried out on 60 patients of CLD. Along with other physical findings and laboratory investigations, 24 hours urinary copper excretions were estimated before and after penicillamine challenge. Study results were analyzed statistically. Thirty CLD patients who fulfilled the inclusion and exclusion criteria of WD were considered as cases (Group I) and remaining 30 CLD patients were considered as non-Wilsonian CLD and was labeled as control (Group II). Among the control group, 12 CLD patients were found to be HBsAg positive, 1 had hepatitis-C virus infection, 1 had autoimmune hepatitis and the remaining 16 CLD patients were Cryptogenic. The (mean±SD) age of WD patients was 9.90±28 years; male female ratio was 1.5:1. Most common presentation was ascites (70%). K-F ring was found in 86.7% cases. Serum ceruloplasmin level was found significantly lower in WD patients (mean±SD, 0.1197±23g/L, p<0.001). Baseline urinary copper excretion of WD patients differed significantly from controls (Median 219.0µg/24hour, range 35-2018µg/24hour, versus median 44µg/24hour, range 20-238µg/24hour, p<0.001). Baseline urinary copper excretion above 100µg/24hour was observed in 80% WD patients whereas it was 10% in controls. post penicillamine urinary copper excretion was significantly greater in WD patients than controls (Median 2635µg/24hour, range 648-6222µg/24hour, versus median 423µg/24hour, range 91-1250µg/24hour, p<0.001). Post penicillamine urinary copper above 1600µg/24hour observed in 70% of WD patients whereas not a single patient reached the value in control group. Twenty four hours urinary copper estimation after penicillamine challenge was found to be a valuable test in the diagnosis of WD.

Wilson's disease in children with blindness: an atypical presentation.

Wilson's disease (WD) is an autosomal recessive disease affecting copper metabolism causing copper induced organ damage. Common organs involved are liver and central nervous system. But RBC, eye, kidneys and bone may also be affected. In WD main defect remains in copper transporter protein p type ATPase resulting from gene mutation in chromosome 13. Neurological manifestations in WD develop due to deposition of copper in different brain areas like basal ganglia, cerebral cortex, corticospinal and corticobulbar pathway. Different types of neurological manifestations develop in WD but visual impairment is very rare. A 14 years old boy of WD presented to us with blindness, tremor and slurred speech along with end stage liver disease. Blindness was thought to be due to optic neuropathy which reversed after drug treatment.