Whole-exome sequencing for genetic diagnosis of idiopathic liver injury in children.

Genome-wide approaches, such as whole-exome sequencing (WES), are widely used to decipher the genetic mechanisms underlying inter-individual variability in disease susceptibility. We aimed to dissect inborn monogenic determinants of idiopathic liver injury in otherwise healthy children. We thus performed WES for 20 patients presented with paediatric-onset recurrent elevated transaminases (rELT) or acute liver failure (ALF) of unknown aetiology. A stringent variant screening was undertaken on a manually-curated panel of 380 genes predisposing to inherited human diseases with hepatobiliary involvement in the OMIM database. We identified rare nonsynonymous variants in nine genes in six patients (five rELT and one ALF). We next performed a case-level evaluation to assess the causal concordance between the gene mutated and clinical symptoms of the affected patient. A genetic diagnosis was confirmed in four rELT patients (40%), among whom two carried novel mutations in ACOX2 or PYGL, and two had previously-reported morbid variants in ABCB4 or PHKA2. We also detected rare variants with uncertain clinical significance in CDAN1, JAG1, PCK2, SLC27A5 or VPS33B in rELT or ALF patients. In conclusion, implementation of WES improves diagnostic yield and enables precision management in paediatric cases of liver injury with unknown aetiology, in particular recurrent hypertransaminasemia.

SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation.

BACKGROUND: Pediatric acute liver failure (PALF) with undetermined etiology is associated with higher liver transplantation and lower spontaneous recovery (transplant-free) rates. The diagnostic odyssey in PALF cases hinders appropriate management and follow-up after liver transplantation. Advances in whole exome sequencing analysis have already been successful at identifying new genetic causes of PALF. CASE PRESENTATION: We report a 17-year-old girl who underwent liver transplantation at the age of 7 months due to acute liver failure and presented later with abnormal neurological manifestations, that is, gait disturbances, dysarthria, and mental retardation that led us to the diagnosis of SCYL1 deficiency. CONCLUSION: PALF cases should be screened for possible underlying genetic disorders. Genetic studies and reanalysis of whole-genome sequencing data may help identify new cases and clarify the genotype-phenotype correlation. SCYL1 deficiency should be suspected in PALF patients who develop neurological involvement after LT. Early diagnosis is vital for proper management of ALF crises in SCYL1 deficiency patients. Despite the reported favorable outcomes of ALF crises in SCYL1 deficiency, liver transplantation decision should be discussed on a case-by-case basis.

Food protein-induced allergic proctocolitis in infants is associated with low serum levels of macrophage inflammatory protein-3a.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is a nonimmunoglobulin (IgE)-mediated food hypersensitivity and the exact mechanisms that cause FPIAP are unknown. Chemokines play crucial roles in the development of allergic diseases. OBJECTIVE: To examine serum levels of a group of chemokines in infants with FPIAP. METHODS: In 67 infants with FPIAP and 65 healthy infants, we measured serum levels of mucosa-associated epithelial chemokine (MEC/CCL28), thymus-expressed chemokine (TECK/CCL25), CX3CL1 and macrophage inflammatory protein (MIP)-3a/CCL20. RESULTS: Infants with FPIAP had a lower median value of MIP3a/CCL20 than healthy infants [0.7 (0-222) vs. 4 (0-249) pg/mL, respectively] (p < 0.001). Infants with MIP3a/CCL20 levels ≤0.95 pg/mL have 13.93 times more risk of developing FPIAP than infants with MIP3a/CCL20 levels >0.95 pg/mL. Serum MEC/CCL28, TECK/CCL25, and CX3CL1 levels were similar between the infants with FPIAP and the control group. CONCLUSION: MIP3a/CCL20 serum levels were reduced in infants with FPIAP compared with healthy controls. Whether this finding has a role in pathogenesis remains to be determined.

Expected Life Expectancy on Liver Transplantation and Aging Donor.

In this study, our aim was to show the life expectancy according to donor age groups at 1, 3, 5, 10, 15, and 20 years after liver transplant in liver transplant recipients. In this retrospective study, we analyzed the survival rate of 236 patients who had liver transplant procedures between 1988 and 2021. The 5-year life expectancy of recipients with donors over age 50 years in the literature has been shown to vary between 50% and 80%. Little information could be found on life expectancy after 10, 15, and 20 years in other studies. In the studies from Haberal and colleagues, life expectancy at 10, 15, and 20 years was 49%, 42%, and 42%, respectively. This study presents an evidence-based example of the use of elderly donors to enlarge the donor pool.

Long-Term Social Outcomes of Pediatric Liver Transplant Recipients: Transition From Childhood to Adulthood.

OBJECTIVES: Chronic disorders may negatively affect people's learning status, marital status, occupational life, and social life. Liver transplant is the only curative treatment for chronic liver diseases. This study was undertaken to evaluate the psychosocial effects of liver transplant in adult patients who had undergone liver transplant during the pediatric period compared with psychosocial facts in the general population. MATERIALS AND METHODS: We retrospectively reviewed adult patients (>18 years of age) who had received liver transplant as children. We compared sex, age at the time of transplant, current age, type of donor, graft survival status, marital status, age at first delivery, number of children, educational status, and occupational status in the study population versus the general (normal) population. To compare the liver transplant patients included in the study with the general population correctly, we used data from the Turkish Statistical Institute. RESULTS: Among 77 liver transplant patients included in our study, the mean age at transplant was 10.9 years (range, 0.5-16 y) and the mean age at the time of the study was 25.2 years (range, 18-42 y). Of the patients, 61 (79.2%) were single and 16 (20.8%) were married. Patients in the study population married at a younger age than the general population (25.5 vs 28.1 y for men, 24.3 vs 25.4 y for women). Of 16 married patients, 9 (56.2%) had a healthy child or children. The percentage of patients who graduated from higher education or were continuing their higher education process was higher in our study population than in the general population (36.3% vs 22.8%). Among our study population, 37 patients (48%) were workers. CONCLUSIONS: Liver transplant had no negative effects on the social, educational, and professional lives among adults in our study who received transplants in the pediatric period.