Efficacy and safety of D-penicillamine, trientine, and zinc in pediatric Wilson disease patients.

OBJECTIVES: Wilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract's copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood. METHODS: Ninety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan-Meier analysis. RESULTS: The median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p < 0.05). Regarding drug changes due to adverse effects, the rate was the highest for DPA, followed by zinc and trientine. There were significant differences between DPA and zinc, zinc and trientine (all p < 0.05), but no significant difference was observed between DPA and zinc (p = 0.22). CONCLUSIONS: In pediatric WD, DPA, zinc, and trientine have therapeutic effects in that order. However, DPA and zinc are associated with more adverse effects compared to trientine.

ACTG2 Variants in Pediatric Chronic Intestinal Pseudo-obstruction With Megacystis.

BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) is a clinically heterogeneous syndrome characterized by compromised peristalsis and intestinal obstruction. Variants of actin gamma 2 (ACTG2), a protein crucial for correct enteric muscle contraction, have been found in CIPO patients. The aim of this study is to examine the clinical features and ACTG2 variants in Korean patients with CIPO. METHODS: From January 1995 to August 2020, 12 patients diagnosed with CIPO were included and genetic analysis testing of ACTG2 was performed. RESULTS: Heterozygous ACTG2 missense variants were found in 6 patients (50.0%). The p.Arg257Cys variant was found in 3 patients, and p.Arg63Gln and p.Arg178His variants were found in 1 patient each. A novel variant, p.Ile193Phe, was found in 1 patient. Three patients were diagnosed at birth, 2 at the age of 1 year, and 1 at 3 years of age. Abnormal prenatal genitourinary ultrasonographic findings were found in all 6 patients; microcolon was found in 4 patients (66.7%), and megacystis in all 6 patients. The pathology showed abnormal ganglion cells as well as myopathic findings. All patients are dependent on total parenteral nutrition and are to date alive. CONCLUSIONS: ACTG2 variants are commonly found in Korean patients with CIPO. In CIPO patients with megacystis and abnormal prenatal ultrasonography, genetic testing of ACTG2 should be considered. Molecular diagnosis of CIPO is more important than pathologic diagnosis.

Use of Anti-TNF Alpha Blockers Can Reduce Operation Rate and Lead to Growth Gain in Pediatric Crohn's Disease.

PURPOSE: Pediatric Crohn's disease (CD) is directly related to growth and has a high probability of requiring surgical intervention(s); therefore, more active treatment for CD is required for children. This study investigated the impact of biologics on growth and disease course associated with surgery. METHODS: This was a retrospective cohort study involving patients diagnosed with CD at the Seoul National University Children's Hospital (Seoul, Korea) between January 2006 and October 2017. The aim was to determine the characteristics of pediatric patients with CD and whether biologics affected growth and the surgical disease course. RESULTS: Among patients who underwent surgery for CD, the mean number of operations per patient was 1.89. The mean time from initial diagnosis to surgery was 19.3 months. The most common procedure was fistulectomy (34%), followed by incision and drainage (25%). In all patients, the use of biologics increased the height (p=0.002) and body mass index (BMI) (p=0.005). Among patients who underwent surgery, height (p=0.004) and BMI (p=0.048) were increased in the group using biologics. Patients who used biologics exhibited a low operation rate only within 2 years after diagnosis, with no differences thereafter (p=0.027). CONCLUSION: Although biologics could not mitigate the operation rate in pediatric patients who underwent surgery for CD, biological therapy delayed disease progression within 2 years of disease onset. Additionally, biologics conferred growth and BMI benefits in this window period. Therefore, it may be helpful to use biologics for optimal growth in pediatric patients with a high probability of undergoing future surgery.

Benign Recurrent Intrahepatic Cholestasis Type 2 in Siblings with Novel ABCB11 Mutations.

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.