ABSTRACT
BACKGROUND/OBJECTIVES: The hepatic prognosis of long-term home total parenteral nutrition (TPN)-dependent children is poorly documented. The objective was to study outcome data in home TPN-dependent children and to describe precisely their liver biopsies in the attempt to analyze risk factors for biochemical and histological hepatic abnormalities. SUBJECTS/METHODS: Medical records of 42 children receiving home TPN for more than 2 years between January 1998 and December 2007 in a single approved home total parenteral center were reviewed. Hepatic biochemical abnormalities were analyzed. Hepatic biopsies were classified by two independent pathologists. RESULTS: Duration of TPN was 7.9±0.8 years (mean±s.e.m.), with an average age at onset of 1.5±0.5 years. A total of 24 patients (57%) developed biochemical liver abnormalities in an average of 2.9±0.4 years after starting TPN. Risk factors for biochemical abnormalities were younger age at TPN commencement, longer duration of TPN, higher rate of catheter-related infections and higher volume and energy content of TPN. Liver biopsies were carried out in 43% of patients (mean age 3.2±0.9 years). Almost all patients had fibrosis (94%). Risk factors were dependent on each histological abnormality: fibrosis was significantly associated with a shorter length of bowel and a longer duration of TPN; cholestasis correlated with a lower percentage of total parenteral energy intake due to lipids; and steatosis had no risk factor identified. CONCLUSION: Our study reports a high rate of histological liver abnormalities and analyzes risk factors in children who underwent very long-term home TPN.
Subject(s)
Cholestasis/etiology , Fatty Liver/etiology , Liver Cirrhosis/etiology , Parenteral Nutrition, Home Total/adverse effects , Age Factors , Biopsy , Catheter-Related Infections/complications , Child, Preschool , Dietary Fats/administration & dosage , Energy Intake , Female , Humans , Infant , Intestines/anatomy & histology , Lipids/administration & dosage , Liver/pathology , Liver Cirrhosis/epidemiology , Liver Cirrhosis/pathology , Male , Prevalence , Prognosis , Risk Factors , Short Bowel Syndrome/complicationsABSTRACT
Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes.
