The Experience of Using Multipotent Mesenchymal Stromal Cells in the Treatment of Severe Recurrent Cholangitis in Children with Biliary Atresia after Kasai Surgery.

This article describes the experience of application of multipotent mesenchymal stromal cells in the complex therapy of severe recurrent cholangitis in 2 children with biliary atresia after Kasai surgery. In both children, hepatic cellular insufficiency and portal hypertension developed against the background of long-term inflammatory process poorly controlled by standard therapy, which was the indication for liver transplantation. During the course of mesenchymal stromal cells therapy, the relief of the inflammatory process and functional recovery of the liver were achieved. At the time of preparing the article, the follow-up of two children since the start of multipotent mesenchymal stromal cell therapy was 3 years 9 months and 2 years 6 months. No recurrence of cholangitis was observed in the patients during the follow-up period, the liver function was preserved. There are no indications for liver transplantation at this moment. Thus, despite the fact that the mechanisms of therapeutic action of multipotent mesenchymal stromal cells in biliary atresia require further investigation, we obtained promising results suggesting the possibility of using mesenchymal stromal cells in the treatment of postoperative complications in children with biliary atresia.

[Advantages of Kasai procedure through minimally invasive approach in children with biliary atresia (in Russian only)]. / Preimushchestva mini-dostupa pri vypolnenii operatsii Kasai u detei s biliarnoi atreziei.

AIM: To compare early and long-term results of different surgical interventions in children with biliary atresia. MATERIAL AND METHODS: Retrospective analysis included medical records of children with biliary atresia who were treated at the Filatov Munitsipal Children's Hospital and National Medical Research Center for Obstetrics, Gynecology and Perinatology from 2000 to 2018. There were 91 patients. All patients were divided into three groups. Group 1 - conventional Kasai procedure (n=24), group 2 - laparoscopic Kasai surgery (n=45), group 3 - Kasai procedure through minimally invasive approach (n=22). Groups were comparable. RESULTS: Duration of Kasai procedure through minimally invasive approach was 69±12,97 min that was significantly less than in groups 1 and 2 (p1,3=0,006085; p2,3=0,000024). ICU-stay was minimal in group 3 (1.27±0.55 days, p1,3<0,05; p2,3<0,05). Abdominal drainage time was maximal in group 2 (11.28±6.37 days) and minimal in group 3 (5.86±2.39 days, p2,3=0.0002). Early and 2-year postoperative surgical efficiency was similar in all groups. There were no surgical complications in group 3. In group 2 one child had gastrointestinal bleeding followed by successful medication. There were 3 surgical complications in group 3: adhesive intestinal obstruction, small and large intestine perforation and 2 cases of gastrointestinal bleeding. There was one lethal outcome in the first group. Overall annual survival in children with native liver was 81.8%, 2-year - 51.7%. CONCLUSION: Kasai procedure through minimally invasive approach is justified and rational method with certain benefits of open and laparoscopic interventions and can be considered as a method of choice in treatment of children with biliary atresia.

[Congenital hypopituitarism with monosomy of chromosome 18].

Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.Сhromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them.

Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes.

Currently, pathogenic variants in more than 25 nuclear genes, involved in mtDNA maintenance, are associated with human disorders. mtDNA maintenance disorders manifest with a wide range of phenotypes, from severe infantile-onset forms of myocerebrohepatopathy to late-onset forms of myopathies, chronic progressive external ophthalmoplegia, and parkinsonism. This study represents the results of molecular genetic analysis and phenotypes of 102 probands with mtDNA maintenance disorders. So far, this is the largest Russian cohort for this group of diseases. Mutations were identified in 10 mtDNA maintenance genes: POLG (n = 59), DGUOK (n = 14), TWNK (n = 14), TK2 (n = 8), MPV17 (n = 2), OPA3 (n = 1), FBXL4 (n = 1), RRM2B (n = 1), SUCLG1 (n = 1) and TYMP (n = 1). We review a mutation spectrum for the DGUOK and TWNK genes, that can be specific for the Russian population. In 34 patients we measured the blood mtDNA copy number and showed its significant reduction. Novel variants were found in 41 cases, which significantly expands the mutational landscape of mtDNA maintenance disorders.

Visceral symptoms as a key diagnostic sign for the early infantile form of Niemann-Pick disease type C in a Russian patient: a case report.

BACKGROUND: Niemann-Pick disease type C is a rare metabolic disease characterized by progressive neurological deterioration with childhood onset, and often results in premature mortality. Niemann-Pick disease type C has an extremely heterogeneous clinical presentation with a wide range of visceral and neurological signs and symptoms that are not specific to the disease, and which progress over varied periods of time. The incidence and epidemiology of Niemann-Pick disease type C in Russia have not been characterized. We report the case of a Russian newborn with early-infantile onset Niemann-Pick disease type C who displayed prolonged neonatal jaundice and hepatosplenomegaly. CASE PRESENTATION: A 5-year-old white boy born to non-consanguineous Russian parents was originally diagnosed with galactosemia at the age of 2 months based on a raised blood galactose level. A galactose-free and lactose-free diet resulted in achievement of a normal galactose level, but hepatosplenomegaly and cholestatic signs persisted. Liver biopsy results hinted at possible Niemann-Pick disease type C, but differential diagnostic investigations for progressive familial intrahepatic cholestasis type 2 (Byler syndrome) indicated a heterozygous genotype suggestive of this disease. Further, progressive neurological symptoms prompted additional genetic analyses for possible Niemann-Pick disease type C, from which an as-yet unreported combination of known NPC1 gene mutations was identified, and a final diagnosis of Niemann-Pick disease type C was established. The patient subsequently developed typical neurological symptoms of early-infantile Niemann-Pick disease type C, including vertical supranuclear ophthalmoparesis and cerebellar ataxia. Miglustat therapy was initiated 2.5 years ago, and some improvements in movement and speech have since been observed. CONCLUSIONS: This case illustrates the continued challenges associated with diagnosing Niemann-Pick disease type C based on the appearance of nonspecific cholestatic symptoms. Based on this case we recommend examination of all newborns and children who display unexplained cholestasis or isolated splenomegaly/hepatosplenomegaly during the first months of life for other signs of possible Niemann-Pick disease type C.