Long-term follow-up for pediatric intestinal pseudo-obstruction patients in China.

BACKGROUND: Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous and severe group of disorders with a high mortality rate. Patients with PIPO often develop malnutrition and need long-term nutrition support. This study aimed to determine the nutrition status, particularly micronutrients, during the long-term follow-up of patients with PIPO. METHODS: Fifty-eight patients with PIPO were followed up for at least 6 months between January 2008 and December 2020 in our hospital. PIPO was diagnosed based on the European society for pediatric gastroenterology, hepatology, and nutrition consensus. Data on clinical characteristics, medical and surgical management, nutrition support, serum vitamins, and mineral concentrations were collected. The patients were divided into the early-onset PIPO (EO-PIPO; neonatal-onset) and late-onset PIPO (LO-PIPO; infant- or child-onset) groups. RESULTS: The mean follow-up was 29.5 months (6-153 months). The overall survival rate was 63.8% (37 out of 58 participants) (EO-PIPO, 48.6% [17 out of 35 participants]; LO-PIPO, 87.0% [20 out of 23 participants]). Mortality in the EO-PIPO group was higher than in the LO-PIPO group (P = 0.002). Twenty-one patients died, of which 18 (85.7%) patients had EO-PIPO and 14 (66.7%) patients died under 1 year of age. Infection was the major cause of death. Severe malnutrition was observed at baseline and during follow-up in 25 (43.1%) and 6 (16.2%) patients, respectively. At baseline and during follow-up, the zinc deficiency rates were 29.6% and 26.3%, and those of vitamin D were 26.9% and 52.6%, respectively. CONCLUSIONS: Zinc and vitamin D deficiencies are common in patients with PIPO during follow-up. Therefore, additional supplements should be recommended.

Congenital Short-Bowel Syndrome: Clinical and Genetic Presentation in China.

BACKGROUND: Congenital short-bowel syndrome (CSBS) is a rare disorder characterized by retardation of intestinal development. However, it is still not well recognized at present. In this study, the etiological, clinical, and genetic characteristics of CSBS in China were analyzed. METHODS: Nine infants with CSBS were recruited. Full-thickness biopsy findings were evaluated by histopathology. Whole-exome sequencing was performed to identify mutations in patients and their family members. All patients were followed up at >1 year of age. RESULTS: Six of 9 infants had malrotation, and 2 patients had intestinal atresia. The average total small-bowel length was 51.7 (40-75) cm. Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutations were found in 5 patients and were related to decreases in ileal goblet cells and mucous secretion. Among these 5 patients, 3 shared the same mutation (c. 206G>A p.R69H), 1 patient had an exon 3-5 deletion, and 1 patient had the C.655T>G, p.Cys219Gly, and C.389-2A>C. Another case carried a loss-of-function mutation in filamin A (FLNA). In the other 3 patients, no pathogenic mutations in genes related to intestinal development were found. The rate of catheter-related bloodstream infection was 4.3 per 1000 catheter days, and intestinal failure-associated liver disease (IFALD) was 77.8%. The median follow-up duration was 24.1 months. Eight patients were weaned off parenteral nutrition (PN). Six patients still exhibited malnutrition during follow-up. CONCLUSIONS: Infants with CSBS often need long-term PN and remain at risk of SBS-related complications. CLMP and FLNA mutations are associated with CSBS in the Chinese population.

Variants in the Enteric Smooth Muscle Actin γ-2 Cause Pediatric Intestinal Pseudo-obstruction in Chinese Patients.

OBJECTIVES: Pediatric intestinal pseudo-obstruction (PIPO) is a severe gastrointestinal disorder occurring in children, leading to failure to thrive, malnutrition, and long-term parenteral nutrition dependence. Enteric smooth muscle actin γ-2 (ACTG2) variants have been reported to be related to the pathogenesis of PIPO. This study aimed to determine the presence of ACTG2 variants in Chinese PIPO patients. METHODS: Whole-exome sequencing was performed using samples from 39 recruited patients, whereas whole ACTG2 Sanger sequencing was performed using samples from 2 patients. Published data was reviewed to determine the number of pathogenic variants and the genotype related to ACTG2 variants in the Chinese population. RESULTS: A total of 21 Chinese probands were found to carry heterozygous missense variants of ACTG2, among which 20 were de novo. Fifteen probands had p.Arg257 variants (c.770G>A and c.769C>T), and the other 2 probands had c.533G>A (p.Arg178His) and c.443G>T (p.Arg148Leu) variants. Four probands had novel variants c.337C>T (p.Pro113Ser), c.588G>C (p.Glu196Asp), c.734A>G (p.Asp245Gly), and c.553G>T (p.Asp185Tyr). CONCLUSIONS: Variants affecting codon 257 of ACTG2 protein sequence appeared to be frequent in both Chinese and Caucasian PIPO patients, whereas p.Arg178 variants were less common in Chinese patients compared with Caucasian patients. The 4 novel variants in ACTG2 were also found to be related to Chinese PIPO.

Micronutrient deficiencies in pediatric short bowel syndrome: a 10-year review from an intestinal rehabilitation center in China.

PURPOSE: Vitamins and trace elements are essential nutrients for growth and intestinal adaptation in children with short bowel syndrome (SBS). This study aimed to assess micronutrients' status during and after weaning off PN in pediatric SBS. METHODS: This retrospective study evaluated the follow-up of 31 children with SBS between Jan 2010 and Sep 2019. Clinical data were reviewed from the patients' electric medical record. Serum electrolytes, trace elements, vitamin B12, vitamin D, and folate concentrations were collected before and after enteral autonomy. RESULTS: Thirty-one SBS cases were reviewed (median onset age 11 days after birth, 51.6% boys, mean PN duration 4 months, and mean residual small intestine length 58.2 cm). Median duration of follow-up was 10 months (interquartile range [IQR]: 4, 19). The common micronutrient deficiencies were zinc (51.6%), copper (38.7%), vitamin D (32.3%), and phosphorus (25.8%) after the transition to EN. The proportion of patients deficient in vitamin D decreased dramatically from 93.5% to 32.3% (P < 0.001), and serum concentrations of vitamin D increased significantly (27.4 ± 12.3 vs. 60.3 ± 32.9 nmol/l, P = 0.03) after achieving full enteral feeding more than 1 month. Additionally, serum magnesium levels significantly increased (0.76 ± 0.17 vs. 0.88 ± 0.14 mmol/l, P = 0.03). Hemoglobin levels elevated significantly after weaning off PN (104.3 ± 10.7 vs. 117.8 ± 13.7 g/l, P = 0.03). CONCLUSIONS: Micronutrient deficiencies remain a common problem in pediatric SBS through intestinal rehabilitation. Therefore, we strongly recommend supplementation of more vitamin D and trace elements (zinc, copper, and phosphorus) under regular monitoring during long-term intestinal rehabilitation.