exudates and Liver-Failure

Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.

Topics: Asian People; Biomarkers; Citrulline; Citrullinemia; DNA Mutational Analysis; Exons; Fatal Outcome; Female; Genetic Predisposition to Disease; Heredity; Humans; Infant; Infant, Newborn; Jaundice, Obstructive; Liver Failure; Malaysia; Male; Mitochondrial Membrane Transport Proteins; Mutation; Pedigree; Phenotype; Prognosis; Time Factors

To study factors leading to delayed referral in neonatal cholestasis at a tertiary centre in Malaysia.. A prospective, observational study on consecutive infants with neonatal cholestasis referred to a tertiary unit paediatric liver unit in Malaysia.. Thirty-one of the 65 (43%) patients studied encountered delay or had an inappropriate action taken before referral. Factors leading to delayed referral, which adversely affected the outcome of biliary atresia (BA) and neonatal acute liver failure, were repeated reassurances by medical and paramedical staff (n = 17, 26%), failure of hospital services at the referring hospital (n = 7, 11%) and parental refusal for referral (n = 5, 8%). Only three (14%) of the 22 patients who developed liver failure had liver transplantation (LT). The 1-year survival rate with native liver for BA was 35%, while overall 1-year survival rate (native liver and LT) was 41%.. Repeated false reassurance, failure of hospital services and parental refusal all contributed to delayed referral in neonatal cholestasis. In addition to education of medical and public health workers, and parents on the importance of early referral in neonatal cholestasis, health authorities in Malaysia should consider the feasibility of universal stool colour screening in newborn infants to improve the outcome of BA.

Topics: Adult; Attitude of Health Personnel; Biliary Atresia; Cholestasis; Clinical Competence; Dissent and Disputes; Early Diagnosis; Female; Hospitalization; Humans; Infant; Infant, Newborn; Jaundice, Neonatal; Liver Failure; Liver Transplantation; Malaysia; Male; Parents; Professional-Family Relations; Prospective Studies; Referral and Consultation; Survival Analysis; Time Factors; Treatment Outcome