Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial.

BACKGROUND/OBJECTIVES: Evidence regarding the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring's neurodevelopment is not conclusive. SUBJECTS/METHODS: In this analysis, the effect of a reduced n-6:n-3 LCPUFA ratio in the diet of pregnant/lactating women (1.2 g n-3 LCPUFA together with an arachidonic acid (AA)-balanced diet between 15th wk of gestation-4 months postpartum vs control diet) on child neurodevelopment at 4 and 5 years of age was assessed. A child development inventory (CDI) questionnaire and a hand movement test measuring mirror movements (MMs) were applied and the association with cord blood LCPUFA concentrations examined. RESULTS: CDI questionnaire data, which categorizes children as 'normal', 'borderline' or 'delayed' in different areas of development, showed no significant evidence between study groups at 4 (n=119) and 5 years (n=130) except for the area 'letters' at 5 years of age (P=0.043). Similarly, the results did not strongly support the hypothesis that the intervention has a beneficial effect on MMs (for example, at 5 years: dominant hand, fast: adjusted mean difference, -0.08 (-0.43, 0.26); P=0.631). Children exposed to higher cord blood concentrations of docosahexaenoic acid, eicosapentaenoic acid and AA, as well as a lower ratio of n-6:n-3 fatty acids appeared to show beneficial effects on MMs, but these results were largely not statistically significant. CONCLUSIONS: Our results do not show clear benefits or harms of a change in the n-6:n-3 LCPUFA ratio during pregnancy on offspring's neurodevelopment at preschool age. Findings on cord blood LCPUFAs point to a potential influence on offspring development.

Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications.

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature.

Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

Prediction of excessive gestational weight gain from week-specific cutoff values: a cohort study.

OBJECTIVE: To assess the prognostic validity of the Institute of Medicine/National Research Council (IOM/NRC) week-specific cutoff values for inadequate or excessive total gestational weight gain (GWG) by 4-week intervals. STUDY DESIGN: We merged data from two German cohorts (LMU cohort (all maternal-weight categories) and PEACHES cohort (obese women)) to provide information on GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We calculated the prognostic values for suboptimal and excessive GWG according to the IOM/NRC cutoff values. RESULT: The positive predictive values for excessive total GWG for those who experienced excessive GWG early in pregnancy was 70.1% (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal-weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5% (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative predictive value). In overweight and obese women, the negative predictive value was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week 20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with inadequate GWG in the first and second trimester had adequate total final GWG (positive predictive value for total inadequate GWG <50% up to week 16/1 to 20/0 in all groups). CONCLUSION: As women with excessive weight gain can be identified with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values, interventions may be initiated early in pregnancy.

Peripheral monocytes of obese women display increased chemokine receptor expression and migration capacity.

CONTEXT: The activation of peripheral immune cells and the infiltration of immune cells into adipose tissue in obesity are implicated in the development of type 2 diabetes mellitus. OBJECTIVE: The aim of the study was to compare peripheral immune cells from obese and normal-weight women with regard to composition of immune cell subpopulations, surface expression of the chemokine receptors (CCRs) CCR2, CCR3, CCR5, and CXCR3 (chemokine (C-X-C motif) receptor 3) and cell-intrinsic migration capacity. DESIGN: This was a case-control study. SETTING: The study was conducted at a university clinical study center. PATIENTS: Obese females and normal-weight females were included for fluorescence-activated cell sorting analysis and migration assays. MAIN OUTCOME MEASURES: Peripheral blood mononuclear cells were prepared from fasting blood samples and used for fluorescence-activated cell sorting analysis and migration assays. RESULTS: An increase in the percentages of CD14(+)CD16(+) monocytes was observed in obese subjects compared with controls. The CCR profile of monocytes differed significantly in the obese state; in particular, CCR2 levels were increased. In addition, a higher chemotactic activity of monocytes from obese subjects was observed in a migration assay, which was associated with both insulin resistance and CCR2 expression. CONCLUSION: Our results suggest that the enhanced intrinsic migratory capacity of peripheral monocytes in obese women may be due to the increased CCR expression, further supporting a link between peripheral immune cell dysfunction and obesity.

Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.

Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition.

Cholesteryl ester storage disease: an easily missed diagnosis in oligosymptomatic children.

Cholesteryl ester storage disease (CESD) is a rare, autosomal recessively inherited disorder resulting from deficient activity of lysosomal acid lipase (LAL). LAL is the key enzyme hydrolyzing cholesteryl esters and triglycerides stored in lysosomes after LDL receptor-mediated endocytosis. Mutations within the LIPA gene locus on chromosome 10q23.2-q23.3 may result either in the always fatal Wolman disease, where no LAL activity is found, or in the more benign disorder CESD with a reduced enzymatic activity, leading to massive accumulation of cholesteryl esters and triglycerides in many body tissues. CESD affects mostly the liver, the spectrum is ranging from isolated hepatomegaly to liver cirrhosis. Chronic diarrhea has been reported in some pediatric cases, while calcifications of the adrenal glands, the hallmark of Wolman disease, are rarely observed. Hypercholesterolemia and premature atherosclerosis are other typical disease manifestations. Hepatomegaly as a key finding has been reported in all 71 pediatric patients and in 134 of 135 adult cases in the literature. We present a 13-year-old boy with mildly elevated liver enzymes in the absence of hepatomegaly, finally diagnosed with CESD. Under pravastatine treatment, the patient has normal laboratory findings and is clinically unremarkable since 5 years of follow-up. To our knowledge, this is the first pediatric case of genetically and biopsy confirmed CESD without hepatomegaly, suggesting that this diagnosis can be easily missed. It further raises the question about the natural course and the therapy required for this oligosymptomatic form.

Gestational diabetes predicts the risk of childhood overweight and abdominal circumference independent of maternal obesity.

AIM: Gestational diabetes mellitus is believed to be a risk factor for childhood overweight/obesity. We aimed to assess whether this association is either a reflection or independent of confounding by maternal BMI. METHODS: Data from 7355 mother-child dyads of the German Perinatal Prevention of Obesity cohort with full anthropometric information on mothers and children, gestational diabetes and confounding factors were obtained at school entry health examination. We calculated crude and adjusted logistic regression models for the association of gestational diabetes and childhood overweight/obesity and abdominal adiposity defined by age- and sex-specific percentiles for BMI and waist circumference. RESULTS: Among all children (mean age 5.8 years), 8.1% were overweight, 2.6% were obese and 15.5% had abdominal adiposity. The prevalence of overweight (obesity) was 21% (8.2%) in children of mothers with gestational diabetes and 10.4% (2.4%) in children of healthy mothers. Analyses with adjustment for maternal BMI and other potential confounders yielded an odds ratio of 1.81 (95% CI 1.23-2.65) and 2.80 (95% CI 1.58-4.99) for the impact of gestational diabetes on childhood overweight and obesity, respectively. Similar results were obtained for the risk of childhood abdominal adiposity (odds ratio 1.64, 95% CI 1.16-2.33) by maternal gestational diabetes. CONCLUSIONS: The postulated increased risk of overweight and abdominal adiposity in offspring of mothers with gestational diabetes cannot be explained by maternal BMI alone and may be stronger for childhood obesity than for overweight.

Effect of propofol and sevoflurane on acid-base balance during pediatric heart catheterization.

BACKGROUND: Propofol is routinely used for anesthesia during pediatric heart catheterization. Propofol infusion syndrome (PRIS) is a rare, but often fatal complication mainly defined as bradycardia with progress to asystolia during propofol infusion. Metabolic acidosis is regarded as an early warning sign of PRIS. In this study the effect of propofol and sevoflurane on serum base excess, pH and lactate have been examined during pediatric heart catheterization. METHODS: In this prospective randomised study 42 children have been anesthetised for pediatric heart catheterization with propofol (N.=22) or sevoflurane (N.=20) with ethic committee approval. Base excess, pH and lactate were measured by blood gas analysis at the beginning, during and at the end of the procedure. Changes relative to baseline were analysed by paired t-Test with correction for multiple testing. The study was powered to detect a difference of 1.5 mmol.L-1 for base excess and lactate. RESULTS: Base excess (-2.59 [2.33] vs. -4.48 [2.88], P=0.0004, mean [standard deviation]) and pH (7.39 [0.05] vs. 7.36 [0.06], P=0.0008,) changed significantly in in the propofol group but not in the sevoflurane group. The number of patients with base excess < 5.0 increased in the propofol group only from 2 to 10 (P=0.016). Lactate decreased in both groups (1.1 [0.3] vs. 0.9 [0.2], P=0.003 for sevoflurane and 1.0 [0.3] vs. 0.8 [0.3], P=0.0004 for propofol). CONCLUSION: Propofol but not sevoflurane had an effect on base excess and pH during pediatric heart catheterization.

Effects of suboptimal or excessive gestational weight gain on childhood overweight and abdominal adiposity: results from a retrospective cohort study.

BACKGROUND: Defining prenatal modifiable risk factors of childhood overweight and obesity has become critical as the need of primary preventive strategies increases. OBJECTIVE: To investigate the interrelationship between inadequate or excessive gestational weight gain (GWG), according to maternal prepregnancy body mass index (BMI)-specific Institute of Medicine (IOM) recommendations, and childhood overweight and abdominal adiposity. DESIGN: In a retrospective cohort study in Germany, data of 6837 mother-child dyads were obtained from medical records, a questionnaire and by anthropometric measurements of children at school entry. Main exposure was GWG as categorized by the 2009 IOM guidelines and as a continuous variable. Outcome measures were children's overweight and abdominal adiposity defined as ≥ 90 th age- and sex-specific percentiles for BMI and waist circumference, respectively. RESULTS: During pregnancy, more than half of mothers (53.6%) had gained weight excessively. Among the children (mean age: 5.8 years), 10.5% were overweight and 15.1% had abdominal adiposity. A nonlinear relationship between absolute GWG and the risk of offspring overweight and abdominal adiposity was observed. An increased risk of childhood overweight was related to excessive compared with recommended GWG, after adjustment for potential confounders (odds ratio (OR): 1.57, 95% confidence interval (CI): 1.30, 1.91), but not to inadequate GWG. Similar results were obtained for the risk of childhood abdominal adiposity by excessive GWG (OR: 1.39, 95% CI: 1.19, 1.63); there was no association with inadequate GWG. Analyses stratified by maternal prepregnancy BMI category did not suggest effect modification. CONCLUSION: Exceeding the recommended BMI-specific IOM GWG ranges has an adverse impact on the risk of childhood overweight and abdominal adiposity, whereas suboptimal GWG conveys no benefit or risk, reflecting a nonlinear relationship between absolute GWG and the risk of childhood overweight and adiposity. Strategies focussing on the awareness and prevention of excessive GWG and its consequences are justified.

Propionic acidemia: neonatal versus selective metabolic screening.

BACKGROUND: Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse. STUDY DESIGN: Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers. RESULTS: Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients' age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS. CONCLUSION: Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.

Mutation analysis in 54 propionic acidemia patients.

Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Grünert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134% of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.

Efficient and gentle siRNA delivery by magnetofection.

Magnetic force combined with magnetic nanoparticles recently has shown potential for enhancing nucleic acid delivery. Achieving effective siRNA delivery into primary cultured cells is challenging. We compared the utility of magnetofection with lipofection procedures for siRNA delivery to primary and immortalized mammalian fibroblasts. Transfection efficiency and cell viability were analyzed by flow cytometry and effects of gene knockdown were quantified by real-time PCR. Lipofectamine 2000 and magnetofection achieved high transfection efficiencies comparable to similar gene silencing effects of about 80%; the cytotoxic effect of magnetofection, however, was significantly less. Magnetofection is a reliable and gentle alternative method with low cytotoxicity for siRNA delivery into difficult to transfect cells such as mammalian fibroblasts. These features are especially advantageous for functional end point analyses of gene silencing, e.g., on the metabolite level.

GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis.

BACKGROUND: Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients. METHODS: The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation. RESULTS: Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged. CONCLUSION: Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.

Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle.

Deficiency of guanidinoacetate methyltransferase (GAMT), the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. This results in epilepsy, mental retardation, and extrapyramidal movement disorders. Investigation of skeletal muscle by proton and phosphorus magnetic resonance spectroscopy before therapy demonstrated the presence of considerable amounts of creatine and phosphocreatine, and accumulation of phosphorylated guanidinoacetate in a 7-year-old boy diagnosed with GAMT deficiency, suggesting separate mechanisms for creatine uptake and synthesis in brain and skeletal muscle. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.

Subtelomeric deletion of 18p in an adult with paranoid schizophrenia and mental retardation.

Chromosome anomalies are responsible for a significant proportion of patients with mental retardation, and congenital anomalies. Development of new molecular cytogenetic techniques has provided a powerful tool for detection of patients with subtle chromosome abnormalities. Particularly, investigation of the gene-rich subtelomeric regions has generated interest regarding the implications and prevalence of cryptic chromosomal rearrangements. Here we describe an adult with a submicroscopic deletion of 18pter, detected by subtelomeric FISH probe. The patient is a 42-year-old man with a history of developmental delay, moderate mental retardation, and symptoms of paranoid schizophrenia since adolescence. His physical examination is remarkable for only a few dysmorphic findings typically seen in 18p- syndrome (round face, hypertelorism, down-slanted palpebral fissures, temporal narrowing, small hands and feet). He lacks significant short stature, skin changes, and associated anomalies involving internal organs. All known patients with deletions of the short arm of chromosome 18 have either loss of large parts of 18p or of the entire p-arm, or have complex chromosomal rearrangement involving other chromosomes. To our knowledge, this is the first description of a cryptic subtelomeric deletion of 18p and the first case of such a chromosomal anomaly in a patient with schizophrenia. Small subtelomeric chromosomal deletions would be missed by standard G-banded karyotyping. Therefore, FISH analysis using subtelomeric probes should be considered for diagnostic evaluation of patients with psychiatric symptoms and mental retardation in whom the karyotype is normal.

Exercise intolerance, muscle pain and lactic acidaemia associated with a 7497G>A mutation in the tRNASer(UCN) gene.

A 13-year-old girl with non-familial exercise intolerance, muscle pain and lactic acidaemia underwent a muscle biopsy for suspected mitochondrial disease. Muscle morphology showed 25% ragged-red fibres and 80% COX-negative staining. Enzymatic activities of mitochondrially co-encoded respiratory chain enzymes (complexes I, III, and IV) were decreased in muscle but normal in cultured skin fibroblasts. mtDNA analysis revealed the presence of the 7497G>A mutation in the tRNASer(UCN) gene, homoplasmic in skeletal muscle and 90% in leukocytes. Analysis of the mother's mtDNA showed 10% heteroplasmy in blood. It may be concluded that the 7497G>A mutation is associated with a muscle-only disease presentation for which high levels of mutated mtDNA are required. Exercise intolerance and muscle pain in otherwise normal children warrants further mitochondrial evaluation.

"Adult" form of muscular carnitine palmitoyltransferase II deficiency: manifestation in a 2-year-old child.

UNLABELLED: We describe a 6-year-old girl admitted with acute muscular weakness and pain which made her unable to walk. Her parents reported a 4-year history of similar episodes which occurred once or twice a year and always resolved spontaneously. Laboratory investigations showed elevated serum creatine kinase which peaked at day 2 of the attack with 18,600 U/l. Carnitine palmitoyltransferase-II deficiency was suspected based on the determination of serum acylcarnitines by tandem mass spectrometry which showed a characteristic elevation of long-chain C16 and C18:1 acylcarnitines. The diagnosis was confirmed by impaired in-vitro palmitate oxidation in blood and the detection of a homozygous substitution S113L in the carnitine palmitoyltransferase-II gene. CONCLUSION: Carnitine palmitoyltransferase-II deficiency should be included in the differential diagnosis of isolated muscular weakness even when manifesting in early childhood.

Hepatopathy in two infants with short-bowel syndrome and cytomegalovirus infection.

In children with short-bowel syndrome and the need for long-term parenteral nutrition, hepatic dysfunction is a multifactorial phenomenon that has not been completely understood. Alterations in gut motility lead to intraluminal stasis which is thought to be a major etiologic factor for bacterial overgrowth and subsequent cholestasis, especially when the ileocecal valve is absent. We report on two infants with short-bowel syndrome caused by gastroschisis and intestinal atresia. The intestinal lengths after resection were 18 and 55 cm. Long-term parenteral nutrition (PN) was obligatory due to intestinal shortness in the first patient and dilatation of the preatretic bowel segment with ineffective peristalsis in the second patient. Despite multiple trials of enteral nutrition and medical therapy for gut decontamination and stimulation of bowel motility, hepatopathy developed in both patients in a similar period of time and to about the same degree. At the age of 4 and 6 weeks, respectively, increasing bilirubin values were measured. Deterioration of liver function and thrombocytopenia at the age of 3 to 4 months led to the diagnosis of acute cytomegalovirus (CMV) infection. Treatment with ganciclovir followed. Both patients died of acute liver failure at the age of 7 and 9 months, respectively. Additional hepatic injury secondary to CMV infection might have contributed to the rapid deterioration of liver disease. Screening for further hepatotoxic factors, especially infectious etiologies, is therefore recommended in children with short-bowel syndrome. Liver transplantation should be considered early in cases of progressive hepatic dysfunction.