A challenging case of hereditary type 1 tyrosinaemia associated with persistent diarrhoea: Case report and literature review

Hereditary tyrosinaemia type 1 (HT1) is a rare inherited genetic disorder attributed to deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). HT1 may present with diarrhoea in its acute form. We report on a 2.5-year-old Egyptian girl diagnosed with HT1. At the age of 1 year and 9 months, the patient started to have persistent diarrhoea with marked abdominal distension, anorexia and irritability, and with no fever or vomiting. At the onset of diarrhoea, liver synthetic functions deteriorated and ascites progressed, requiring frequent paracentesis. These manifestations did not improve after starting specific treatment for HT1 (2-(2-nitro-4-trifluoromethylbenzoyl)- 1,3-cyclohexanedione) (NTBC). Coeliac disease was diagnosed; this disorder was not previously reported as having an association with HT1

Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation.

Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism characterized by hypermanganesemia, polycythemia, early-onset dystonia, and liver cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been reported. Here, we describe 10 patients from 7 unrelated Egyptian families with HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia hyperintensity on T1-weighted images, and variable degrees of extrapyramidal manifestations with or without liver disease were cardinal features in all patients. Eight patients presented with striking early diseased onset (≤2 years). Unexpectedly, early hepatic involvement before the neurological regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*), c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms. Our findings present a large cohort of patients with HMDPC from same ethnic group. The majority of our patients showed severe and early presentation with clear phenotypic variability among sibship. Moreover, we extend the phenotypic and mutational spectrum and emphasize the importance of early diagnosis and treatment of this potentially fatal disorder.

A child with rotor syndrome and Capillaria philippinensis: case report and review of literature.

This paper reported Capillaria philippinensis in an Egyptian child based on clinical and laboratory diagnosis. The patient was successfullly treated with albendazole.

Anti-HCV prevalence among diabetic and non-diabetic Egyptian children.

Our aim was to determine the prevalence of the HCV infection among children with type 1 DM as compared to a group of non-diabetic children attending the general outpatient clinics of the same hospital and investigate the possible risk factors. The study was carried out on 692 children with type 1 DM attending the Pediatric Diabetes Unit at Cairo University Pediatric Hospital, Egypt, and 1042 non-diabetic children attending the general outpatient clinics of the same hospital. They were screened for HCV antibodies using third generation ELISA. Anti-HCV antibody prevalence in diabetic children below 9 years of age was comparable to that of non diabetic children (2.5% vs. 1.4%; p=0.25). Diabetic children had higher exposure to medical care (p=0.04); all diabetics were exposed to daily insulin injections and daily blood glucose monitoring. Non-diabetics had higher exposure to razors used by others (p=0.05) and higher rate of traditional hair cutting (p=0.05). To conclude, the prevalence of anti-HCV in diabetic children below 9 years of age was comparable to non diabetic children of the same age group. Application of standard precautions for infection control could successfully limit spread of HCV infection in our Pediatric Diabetes Unit, in a country with high HCV load as Egypt.

Cost-effectiveness of prescreening versus empirical vaccination for hepatitis A in Egyptian children with chronic liver disease.

The aim of the study was to determine the prevalence of anti-hepatitis A virus (anti-HAV) antibodies among 172 children with chronic liver disease, and to calculate the cost-effectiveness of prescreening prior to hepatitis A vaccination. Anti-HAV antibodies were positive in 85.1%. However, seroprevalence of anti-HAV antibodies was 62.1% in children < 5 years and 94.4% in children 5+ years. We conclude that while it is cost-effective to do prescreening before hepatitis A vaccination for children with chronic liver disease aged 5+ years, prescreening might not be cost-effective in those aged < 5 years.

Cost-effectiveness of prescreening versus empirical vaccination for hepatitis A in Egyptian children with chronic liver disease

The aim of the study was to determine the prevalence of anti-hepatitis A virus [anti-HAV] antibodies among 172 children with chronic liver disease, and to calculate the cost- effectiveness of prescreening prior to hepatitis A vaccination. Anti-HAV antibodies were positive in 85.1%. However, seroprevalence of anti-HAV antibodies was 62.1% in children < 5 years and 94.4% in children 5+ years. We conclude that while it is cost-effective to do prescreening before hepatitis A vaccination for children with chronic liver disease aged 5+ years, prescreening might not be cost-effective in those aged < 5 years

Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children.

AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver disease. RESULTS: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children.

Post-portoenterostomy triangular cord sign prognostic value in biliary atresia: a prospective study.

The triangular cord sign (TC sign) is a sensitive and specific tool in prompt diagnosis of extrahepatic biliary atresia. The objective of this study is to evaluate post-operative TC sign presence in outcome prediction of infants with biliary atresia after Kasai hepato-portoenterostomy 27 infants and children with biliary atresia underwent 122 ultrasound examinations using both 5 MHz and 7 MHz convex linear transducers in 33 months follow up. For all infants TC sign identification was included pre-operatively, ultrasound was done 2 weeks post-operatively then bimonthly for 3 months, monthly for 2 months and every 3 months thereafter. 14 (53.8%) had post-operative TC sign. Once post-operatively positive, it remained positive throughout the study. It did not reappear in an initially post-operatively TC sign negative infant. Those having post-operative TC sign had statistically worse outcomes (0 became anicteric, 2 improved, 7 had progressive disease and 6 died) than those with a negative TC sign (p = 0.04) (3 became anicteric, 5 improved, 2 progressed and 1 died). Presence of TC sign post-operatively correlated with measure of removal of all fibrous cone at porta-hepatis during portoenterostomy (p = 0.026). Post-portoenterostomy TC sign is associated with more morbidity and mortality; and reflects inadequate surgical technique.

Hepatitis C virus infection in Egyptian children: single centre experience.

The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti-HCV). The data of 105 anti-HCV-positive children presenting to the Pediatric Hepatology Unit, Cairo University Children's Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy-four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3-22 years, with a mean of 11.2 +/- 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti-HBc) were detected in 18 patients (24.3%). Twenty-six of the 43 HCV RNA-positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA-positive cases.

Diagnosis and management of galactosemia: an Egyptian experience.

OBJECTIVE: To screen normal and high risk Egyptian neonates for galactosemia. SUBJECTS AND METHODS: The study included 2238 neonates classified into two groups. Group I included screening of 1794 normal newborns. Group II included 374 high risk neonates (jaundice, hepatomegaly and failure to thrive). Group III 70 prematures. Total galactose was determined by enzymatic colourimetric method in dried blood spot (Quantase). The enzymes activities (uridyltransferase and epimerase) were measured using C14. RESULTS: One case of galactosemia was found in the first group and 26 cases in the second group. 19 patients suffered from uridyltransferase deficiency, the parents of 16 (88.8%) of this classic form were consanguineous and 5 (27.7%) parents had history of a previously affected child. Mean age of diagnosis was 3.8 month with a mean total gal value of 52.9 mg/dl. 10 (55.5%) of them have cataract. The other 8 affected neonates were epimerase deficiency patients. 5 (62.5%) of them born to consanguineous parents. Parents of the epimerase deficiency neonates have no previously affected children. Mean age of diagnosis was 7.2 month with a mean total gal of 17.5 mg/dl. All eight patients have cataract. CONCLUSION: Mass screening program is not available yet in Egypt. Screening of the high risk neonates is a priority. Diagnosis of different galactosemia forms is mandatory to structure the management strategy accordingly. (Fig. 4, Ref: 26.)

Evaluation of the triangular cord sign in the diagnosis of biliary atresia.

BACKGROUND: Infantile cholestasis continues to represent a diagnostic challenge. It is very important to diagnose surgically correctable disorders, such as biliary atresia, in a timely manner to prevent progressive damage to the liver. It has been recently suggested that the triangular cord (TC) sign is a simple and useful tool in the diagnosis of biliary atresia. METHODS: We prospectively studied 65 infants presenting with conjugated hyperbilirubinemia (age range: 32-161 days). All patients underwent ultrasonographic examination with a 7.0-MHz transducer (Acuson, Mountain View, CA). The TC was defined as a triangular, or tubular, echogenic density seen immediately cranial to the portal vein bifurcation. RESULTS: The TC sign was identified in 25 infants, and all of them had histologic features suggestive of biliary atresia; the diagnosis was confirmed at surgery by gross morphology of hepatobiliary system, and liver biopsy, with or without intraoperative cholangiogram. Among the 40 patients who did not have the TC sign, 6 had paucity of the intrahepatic bile ducts. Three had alph-1-antitrypsin deficiency, and 31 had neonatal hepatitis. None of the 40 patients who did not have the TC sign developed acholic stools. Seven patients with biliary atresia were followed by ultrasonographic examination for 6 months after the Kasai procedure. The TC sign disappeared in all patients after the surgery; however, the TC sign reappeared in 3 patients who developed progressive cholestasis after the procedure. CONCLUSION: The TC sign is a simple, timesaving, and reliable diagnostic tool in the evaluation of infants with infantile cholestasis. The TC sign may also prove to be helpful in following patients after hepatoportoenterostomy. We suggest a new diagnostic strategy for patients suspected to have biliary atresia. When the TC sign is visualized, the patient should undergo intraoperative cholangiogram to confirm the diagnosis of biliary atresia, reserving percutaneous liver biopsy for those patients in whom the TC sign could not be detected.

Hepatic dysfunction in children with acute lymphoblastic leukemia in remission: relation to hepatitis infection.

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy. PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children. RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy. CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.

Human fascioliasis in Egyptian children: successful treatment with triclabendazole.

Human fascioliasis (HF) is an increasingly recognized public health problem in Egypt. During the past two years we diagnosed HF in 40 Egyptian children. Diagnosis was based on some or all of the following criteria: fever, tender hepatomegaly and high eosinophilia (febrile eosinophilic syndrome), presence of Fasciola hepatica eggs in stools, and/or serodiagnosis using the indirect haemagglutination test (IHAT). Eight of the 40 children had failed to respond to previous treatment with praziquantel. All children were treated with triclabendazole in a dose of 10 mg/kg as a single oral dose. Within 2 months, 31 children (78 per cent) were cured as evidenced by clinical well-being, normalization of eosinophil counts, Fasciola antibody titres, and absence of Fasciola hepatica eggs in stools. The remaining nine cases achieved clinical and laboratory cure after a second dose of triclabendazole. No side-effects were encountered in any of the cases. We conclude that triclabendazole is an effective, well-tolerated, easy to administer drug that should be considered in HF.

Human fascioliasis: clinical features and diagnostic difficulties in Egyptian children.

Human fascioliasis (HF) has been reported in children worldwide and occasionally from Egypt. In the past 7 years we diagnosed 16 children aged 3.5-11 years (mean age: 6.5 years), 13 of them were boys, as HF. They were referred to Cairo University, Paediatric Hospital (CUPH), with pyrexia of undetermined origin (PUO) and abdominal pain. Diagnosis was based on high peripheral blood eosinophilia (14-82 per cent) in all patients along with Fasciola hepatica egg detection on direct stool smear in three or stool concentration in four, antibody detection by indirect haemagglutination test (IHAT) in seven egg-negative patients and ultrasonographic detection of hepatic and/or biliary lesions of HF in two egg-negative patients. Percutaneous liver biopsy confirmed the diagnosis of an eosinophilic abscess (parasitic granuloma) in 12 of 13 patients. Therefore, HF does occur in Egyptian children and its diagnosis needs a high index of suspicion supported by stool microscopy, serology, imaging procedures, and probably liver biopsy.