Long-Term Effects of Kasai Portoenterostomy for Biliary Atresia Treatment in Russia

This prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyzed the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients had celebrated their 10th birthdays with good quality of life and no indications for transplantation of the liver. The obtained results underscore the critical importance of surgical correction of biliary atresia by Kasai surgery in the first 60 days of life and subsequent dynamic follow-up of patients for the purpose of the early detection and timely correction of possible complications

Clinical Presentation of a Patient with a Congenital Disorder of Glycosylation, Type IIs (<i>ATP6AP1</i>), and Liver Transplantation

The congenital disorder of glycosylation type IIs (ATP6AP1-CDG; OMIM# 300972) is a rare X-linked recessive complex syndrome characterized by liver dysfunction, recurrent bacterial infections, hypogammaglobulinemia, and defective glycosylation of serum proteins. Here, we examine the case of a 1-year-old male patient of Buryat origin, who presented with liver dysfunction. At the age of 3 months, he was hospitalized with jaundice and hepatosplenomegaly. Whole-exome sequencing identified the ATP6AP1 gene missense variant NM_001183.6:c.938A>G (p.Tyr313Cys) in the hemizygous state, which was previously reported in a patient with immunodeficiency type 47. At the age of 10 months, the patient successfully underwent orthotopic liver transplantation. After the transplantation, the use of Tacrolimus entailed severe adverse effect (colitis with perforation). Replacing Tacrolimus with Everolimus led to improvement. Previously reported patients demonstrated abnormal N- and O-glycosylation, but these data were collected without any specific treatment. In contrast, in our patient, isoelectric focusing (IEF) of serum transferrin was performed only after the liver transplant and showed a normal IEF pattern. Thus, liver transplantation could be a curative option for patients with ATP6AP1-CDG

Influence of Plant Growth Regulators and Artificial Light on the Growth and Accumulation of Inulin of Dedifferentiated Chicory (Cichorium intybus L.) Callus Cells

Chicory (Chicorium intybus L.) is a perennial herb of the family Asteraceae, widely distributed in Asia and Europe, commonly used industrially as a raw material for extracting inulin because of a high content of inulin and biologically active compounds. Light conditions and plant growth regulators (PGRs) are two of many factors that affect the growth and inulin content of chicory callus. The aim of this work is to study the effect of PGRs and light conditions on proliferation and accumulation of inulin of chicory callus in vitro. In this study, we used semi-solid MS medium supplemented with different auxins (including Indole-3-acetic acid (IAA), naphthylacetic acid (NAA), and 2,4-dichlorophenoxyacetic acid (2,4-D)) at a concentration of 5.5&ndash;9.5 mg/L in combination with 2.0 mg/L 6 benzylaminopurine (BA) to determine induction and proliferation of callus. The increasing value of callus fresh weight was used to assess the growth of the callus in treatments. The results showed that a steady increase in callus fresh weight and inulin content in callus cells was obtained when they were cultured on MS medium supplemented with a combination of 2.0 mg/L BA with 7.5 mg/L IAA in lighting conditions with radiation equalized by the flux density of photosynthetic photons and ratios of radiation levels in the region of FR&mdash;far red &gt; R&mdash;red. Increasing demand for organic inulin sources in production practice can be met by our finding

De Novo Variant in the <i>KCNJ9</i> Gene as a Possible Cause of Neonatal Seizures

Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented with convulsive syndrome on the third day of life. Generalized convulsive seizures were accompanied by electroencephalographic patterns corresponding to epileptiform activity. Proband WES expanded to trio sequencing was performed. Results: A differential diagnosis was made between symptomatic (dysmetabolic, structural, infectious) neonatal seizures and benign neonatal seizures. There were no data in favor of the dysmetabolic, structural, or infectious nature of seizures. Molecular karyotyping and whole exome sequencing were not informative. Trio WES revealed a de novo variant in the KCNJ9 gene (1:160087612T > C, p.Phe326Ser, NM_004983), for which, according to the OMIM database, no association with the disease has been described to date. Three-dimensional modeling was used to predict the structure of the KCNJ9 protein using the known structure of its homologs. According to the predictions, Phe326Ser change possibly disrupts the hydrophobic contacts with the valine side chain. Destabilization of the neighboring structures may undermine the formation of GIRK2/GIRK3 tetramers necessary for their proper functioning. Conclusions: We believe that the identified variant may be the cause of the disease in this patient but further studies, including the search for other patients with the KCNJ9 variants, are needed

The hidden Niemann-Pick type C patient:Clinical niches for a rare inherited metabolic disease

Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (clinical niches) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Methods: Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Findings: Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Conclusions: Several clinical niches have been identified that harbor patients at increased risk of NP-C

The hidden Niemann-Pick type C patient : clinical niches for a rare inherited metabolic disease

BACKGROUND : Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (“clinical niches”) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. METHODS : Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. FINDINGS : Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. CONCLUSIONS : Several clinical niches have been identified that harbor patients at increased risk of NP-C.Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. From Actelion Pharmaceuticals Ltd.: travel expenses AC, AD, AP, CD-V, CJH, CL, HHK, MT, MW, MP, MS, PB, OB, SD, SL; research funding AP, CL, CD-V, CJH, FT-B, J-CC, MW, OB, PB, RI, SD, TD, TdK; consultancy fees AP, CJH, CL, HHK, MT, MW, OB, PB, SL; speaker honoraria CD-V, MP, MS, PB, SD. MA has received speaker honoraria and travel expenses from Abbvie, TEVA, and UCB. J-CC has received speaker honoraria from Abbvie, travel grants from Abbvie, research funding from, Ipsen, and the Michael J Fox Foundation, and consultancy fees from BMS, Zambon, Pfizer, Amarantus, Clevexel, and Abbvie. CD-V has received research grants, investigator fees, speaker honoraria, and travel expenses from Sanofi Genzyme, Orphan Europe, and Nutricia. SD has received research funding from TEVA. CJH is Director of FYMCA Medical Ltd., has received consultancy fees and travel expenses from Alexion, Amicus, Biomarin, Inventiva, Sanofi Genzyme, and Shire, and has undertaken paid research on behalf of Amicus, Biomarin, Sanofi Genzyme and Shire. SL has received consultancy fees and travel expenses from TEVA, Boehringer, Gruenenthal, and UCB6e. AP has received research funding, consultancy fees and travel expenses from Eli-Lilly, GE Health, and Lundbeck. CT has received speaker honoraria and travel expenses from Abbvie, Zambon, TEVA, and UCB. CV and SK are employees of Actelion Pharmaceuticals Ltd.http://www.tandfonline.com/loi/icmo202018-03-02hj2018Paediatrics and Child Healt