Cardiac involvement (CI) in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG) is part of the multisystemic presentation contributing to high mortality rates. The most common cardiac manifestations are pericardial effusion, cardiomyopathy, and structural heart defects. A genotype-phenotype correlation with organ involvement has not yet been described. We analyzed clinical, biochemical, and molecular genetic data of 222 patients from eight European centers and characterized the natural course of patients with CI. Fifty-seven patients (45 children) presented with CI, of whom 24 died (median age 21 months, standard deviation 49.8). Pericardial effusion was the most frequent manifestation (55.4%), occurring mostly within the first 6 months of life. The most common pathogenic variants in patients with CI were p.(Arg141His) in 74%, followed by p.(Val231Met) in 36%, which is 3.5 times higher than in PMM2-CDG patients without CI (p < 0.0001). Twenty-one out of 36 patients with p.(Val231Met) had CI; among them, 15 died, compared to 33 out of 166 patients without p.(Val231Met) who had CI (p < 0.0001). Nine out of 33 patients died (p = 0.0015), indicating greater clinical severity. Furthermore, the p.(Val231Met) variant is predominant in Eastern Europe, suggesting a founder effect. Cardiac complications in PMM2-CDG patients are common and serious. The variant p.(Val231Met) profoundly influences the extent of CI and mortality rates. Therefore, we recommend cardiac surveillance be included in the follow-up protocols for PMM2-CDG.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• fosfotransferasy (fosfomutasy) * genetika   nedostatek   MeSH
• genetické asociační studie MeSH
• kardiomyopatie genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• vrozené poruchy glykosylace * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Advances in paediatric type 1 diabetes management and increased use of diabetes technology have led to improvements in glycaemia, reduced risk of severe hypoglycaemia, and improved quality of life. Since 1993, progressively lower HbA1c targets have been set. The aim of this study was to perform a longitudinal analysis of HbA1c, treatment regimens, and acute complications between 2013 and 2022 using data from eight national and one international paediatric diabetes registries. METHODS: In this longitudinal analysis, we obtained data from the Australasian Diabetes Data Network, Czech National Childhood Diabetes Register, Danish Registry of Childhood and Adolescent Diabetes, Diabetes Prospective Follow-up Registry, Norwegian Childhood Diabetes Registry, England and Wales' National Paediatric Diabetes Audit, Swedish Childhood Diabetes Registry, T1D Exchange Quality Improvement Collaborative, and the SWEET initiative. All children (aged ≤18 years) with type 1 diabetes with a duration of longer than 3 months were included. Investigators compared data from 2013 to 2022; analyses performed on data were pre-defined and conducted separately by each respective registry. Data on demographics, HbA1c, treatment regimen, and event rates of diabetic ketoacidosis and severe hypoglycaemia were collected. ANOVA was performed to compare means between registries and years. Joinpoint regression analysis was used to study significant breakpoints in temporal trends. FINDINGS: In 2022, data were available for 109 494 children from the national registries and 35 590 from SWEET. Between 2013 and 2022, the aggregated mean HbA1c decreased from 8·2% (95% CI 8·1-8·3%; 66·5 mmol/mol [65·2-67·7]) to 7·6% (7·5-7·7; 59·4mmol/mol [58·2-60·5]), and the proportion of participants who had achieved HbA1c targets of less than 7% (<53 mmol/mol) increased from 19·0% to 38·8% (p<0·0001). In 2013, the aggregate event rate of severe hypoglycaemia rate was 3·0 events per 100 person-years (95% CI 2·0-4·9) compared with 1·7 events per 100 person-years (1·0-2·7) in 2022. In 2013, the aggregate event rate of diabetic ketoacidosis was 3·1 events per 100 person-years (95% CI 2·0-4·8) compared with 2·2 events per 100 person-years (1·4-3·4) in 2022. The proportion of participants with insulin pump use increased from 42·9% (95% CI 40·4-45·5) in 2013 to 60·2% (95% CI 57·9-62·6) in 2022 (mean difference 17·3% [13·8-20·7]; p<0·0001), and the proportion of participants using continuous glucose monitoring (CGM) increased from 18·7% (95% CI 9·5-28·0) in 2016 to 81·7% (73·0-90·4) in 2022 (mean difference 63·0% [50·3-75·7]; p<0·0001). INTERPRETATION: Between 2013 and 2022, glycaemic outcomes have improved, parallel to increased use of diabetes technology. Many children had HbA1c higher than the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 target. Reassuringly, despite targeting lower HbA1c, severe hypoglycaemia event rates are decreasing. Even for children with type 1 diabetes who have access to specialised diabetes care and diabetes technology, further advances in diabetes management are required to assist with achieving ISPAD glycaemic targets. FUNDING: None. TRANSLATIONS: For the Norwegian, German, Czech, Danish and Swedish translations of the abstract see Supplementary Materials section.

• MeSH
• diabetes mellitus 1. typu * epidemiologie   krev   farmakoterapie   MeSH
• dítě MeSH
• glykovaný hemoglobin * analýza   MeSH
• hypoglykemie epidemiologie   MeSH
• hypoglykemika * terapeutické užití   MeSH
• kojenec MeSH
• krevní glukóza * analýza   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• předškolní dítě MeSH
• registrace * statistika a číselné údaje   MeSH
• regulace glykemie statistika a číselné údaje   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype. PROCEDURE: We report diagnostic and follow-up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T-cell precursor (ETP, n = 7); or T-ALL (ETP status unknown, n = 2), ALAL (acute leukemia of ambiguous lineage, n = 1), and AML reclassified from ALAL (n = 1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data. RESULTS: Among the four patients who started and remained on ALL-type therapy, all were in the first complete remission, whereas both patients who started and remained on AML-type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow-up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia. CONCLUSIONS: Briefly, ALL- or combined ALL/AML-type therapy may be effective for treating AuR-positive leukemia patients with a lymphoid immunophenotype.

• MeSH
• akutní lymfatická leukemie patologie   terapie   imunologie   MeSH
• akutní myeloidní leukemie patologie   terapie   imunologie   MeSH
• dítě MeSH
• imunofenotypizace * MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ1-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6-oxo-pipecolic acid (6-oxo-PIP) also accumulates in the urine, CSF and plasma of ALDH7A1-deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6-oxo-PIP in urine from a cohort of 30 patients where α-AASA was elevated and showed that it was above the normal range in all those above 6 months of age. However, 6-oxo-PIP levels were within the normal range in 33% of the patients below 6 months of age. Levels increased with age and correlated with a decrease in α-AASA levels. Longitudinal analysis of urine samples from ALDH7A1-deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6-oxo-PIP remained elevated whilst α-AASA decreased. Similar to α-AASA, we found that elevated urinary excretion of 6-oxo-PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6-oxo-PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long-term side effects.

• MeSH
• aldehyddehydrogenasa nedostatek   genetika   MeSH
• biologické markery * moč   MeSH
• dítě MeSH
• epilepsie moč   MeSH
• kojenec MeSH
• kyselina 2-aminoadipová moč   analogy a deriváty   MeSH
• kyseliny pipekolové * moč   MeSH
• lidé MeSH
• lysin nedostatek   moč   MeSH
• mitochondriální aldehyddehydrogenasa nedostatek   genetika   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• pyridoxin nedostatek   moč   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.

• MeSH
• dítě MeSH
• DNA MeSH
• epilepsie * komplikace   MeSH
• fokální kortikální dysplazie * MeSH
• komplex proteinů jaderného póru * MeSH
• lidé MeSH
• midazolam MeSH
• molekulární chaperony * MeSH
• nemoci mozku * MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• refrakterní epilepsie * genetika   chirurgie   MeSH
• status epilepticus * genetika   chirurgie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Úvod: Cílem studie bylo určit rozsah renálního poškození podle gradingu 99mTc-DMSA scanu u dětí s vezikoureterálním refluxem (VUR) III. stupně, který je částí odborné veřejnosti považován spolu s VUR I. a II. stupně za nízkostupňový. Metody: Celkem bylo vyšetřeno 132 pacientů (56 chlapců a 76 dívek ve věku 6 měsíců až 11 let) s diagnózou VUR různého stupně 6 měsíců po akutní pyelonefritidě. Statická scintigrafie ledvin byla provedena 2 hodiny po i.v. podání 18–80 MBq 99mTc-DMSA. Stanovení stupně postižení ledvin bylo provedeno podle počtu postižených segmentů ledviny (0–12) na základě gradingu 99mTc-DMSA G0-G4 (Mattoo et al), s naší modifikací stupně G4. V každé postižené ledvině byl hodnocen počet patologických segmentů/jizev. Průměr hodnot v rámci každého stupně VUR byl vyhodnocen pomocí Studentova t-testu. Výsledky: Hodnoceno celkem 201 ledvin s VUR, významně vyšší počet jizev byl prokázán u VUR III. stupně než u zbylých nízkostupňových stupňů (2,88 vs. 1,58, p = 0,002). Na druhou stranu, ve srovnání se IV. stupněm VUR, se jednalo o nevýznamně nižší hodnotu (2,88 vs. 3,51, p = 0,08). Ve srovnání s VUR IV. a V. stupně byla hodnota statisticky významně nižší (3,99 vs. 2,88, p = 0,004). Závěr: VUR III. stupně je spojen s vyšším rozsahem parenchymových změn (podle 99mTc-DMSA gradingu) ve srovnání s VUR I. a II. stupně. 99mTc-DMSA grading může demaskovat závažnější případy VUR III. stupně, který proto doporučujeme vyčlenit a hodnotit jako samostatný stupeň. Korespondující autorka: MUDr. Daniela Chroustová, Ph.D. Ústav nukleární medicíny VFN a 1. LF UK Praha U nemocnice 5 128 08 Praha 2

Introduction: The aim of this study was to determine the risk of renal damage in children diagnosed with vesico-ureteral reflux (VUR) grade III, which is generally considered as a low-grade VUR, according to the occurrence of renal changes using the 99mTc-DMSA scan grading. Methods: A total of 132 patients with VUR were examined (56 boys, 76 girls aged 6 months -11 years) 6 months after acute pyelonephritis with. Static renal scintigraphy was performed 2 h after i.v. administration of 18-80 MBq 99mTc-DMSA. Determination of the degree of kidney involvement according to the 99mTc-DMSA grading G0-G4 (Mattoo et al) was based on the number of affected segments (0-12). The number of pathological segments/scars was assessed in each involved kidney. Mean values within each VUR grade were evaluated using Student’s t-test. Results: 200 kidneys were evaluated. VUR III. grade demonstrated significantly higher value of scars (2.88 vs 1.58, p = 0.002) than the remaining low-risk grades I and II. On the other hand, when compared with high-risk grade IV, the value was not significantly lower (2,88 vs. 3,51, p = 0,08). In comparing VUR III. with VUR IV.-V. grades, there was a significantly higher number of scars in high-grade VUR. (3.99 vs. 2.88, p = 0.004). Conclusion: VUR III. grade is associated with a higher extend of parenchymal changes (according to 99mTc-DMSA grading) compared to low grades VUR I. and II. 99mTc-DMSA grading can unmask more severe cases of VUR III. degree, which we therefore recommend separating and evaluating as a separate degree.

• MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• nemoci ledvin diagnostické zobrazování   klasifikace   patologie   MeSH
• předškolní dítě MeSH
• pyelonefritida diagnóza   etiologie   prevence a kontrola   MeSH
• radioisotopová scintigrafie klasifikace   metody   MeSH
• renální insuficience diagnostické zobrazování   diagnóza   etiologie   klasifikace   MeSH
• retrospektivní studie MeSH
• technecium 99mTc dimerkaptojantarová kyselina * analýza   metabolismus   MeSH
• vezikoureterální reflux * diagnostické zobrazování   diagnóza   klasifikace   komplikace   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH

OBJECTIVE: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

• MeSH
• bazální ganglia * MeSH
• dítě MeSH
• dospělí MeSH
• kavernózní hemangiom centrálního nervového systému * chirurgie   radioterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• radiochirurgie * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• thalamus * chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The diagnostic prevalence of autism spectrum disorders (ASD) shows boys to be more affected than girls. Due to this reason, there is a lack of research including and observing ASD girls. Present study was aimed to detect hormones of steroidogenesis pathway in prepubertal girls (n = 16) diagnosed with ASD and sex and age matched neurotypical controls (CTRL, n = 16). Collected plasma served for detection of conjugated and unconjugated steroids using gas chromatography tandem-mass spectrometry. We observed higher levels of steroids modulating ionotropic receptors, especially, GABAergic steroids and pregnenolone sulfate in ASD group. Concentration of many steroids throughout the pathway tend to be higher in ASD girls compared to CTRL. Pregnenolone and its isomers together with polar progestins and androstanes, i.e. sulfated steroids, were found to be higher in ASD group in comparison with CTRL group. Based on steroid product to precursor ratios, ASD group showed higher levels of sulfated/conjugated steroids suggesting higher sulfotransferase or lower steroid sulfatase activity and we also obtained data indicating lower activity of steroid 11β-hydroxylase compared to CTRL group despite higher corticosterone level observed in ASD. These findings need to be generalized in future studies to examine both genders and other age groups.

• MeSH
• dítě MeSH
• lidé MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• poruchy autistického spektra * metabolismus   MeSH
• předškolní dítě MeSH
• pregnenolon * metabolismus   krev   MeSH
• steroidy metabolismus   krev   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Postoperative constipation (PC) in patients with imperforate anus and perineal fistula (PF) has been reported in up to 60%. Histological studies of PF revealed innervation anomalies which seem to be one of the reasons for PC. Perioperative histologically controlled fistula resection (PHCFR) allows appropriate resection of PF and pull-down normoganglionic rectum at the time of posterior sagittal anorectoplasty (PSARP). MATERIALS AND METHODS: A total of 665 patients with anorectal malformations underwent surgery between 1991 and 2021. Of these, 364 presented PF; 92 out of them (41 F) were studied. Patients with sacral and spinal cord anomalies, neurological disorders, and cut-back anoplasty were excluded. PSARP was done on all patients. Hematoxylin-eosin staining and NADH Tetrazolium-reductase histochemical method were used. Four and more ganglion cells in the myenteric plexus represented a sufficient length of the resection. The continence was scored according to the modified Krickenbeck scoring system. Final scores ranged from 1 to 7 points. Values are given as median. RESULTS: A total of 65 (70.7%) patients presented an aganglionic segment in PF, and 27 patients presented hypoganglionosis. The median length of the resected fistula was 25 mm (interquartile range [IQR]: 20-30). The median total continence score was 7 (IQR: 6-7). Post-op constipation was observed in 6/92 (6.5%) patients. CONCLUSION: PHCFR diminished PC to 6.5% of patients.

• MeSH
• anální atrézie * chirurgie   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• perineum chirurgie   MeSH
• pooperační komplikace etiologie   MeSH
• předškolní dítě MeSH
• rektální píštěl * chirurgie   MeSH
• rektum chirurgie   abnormality   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• zácpa etiologie   chirurgie   MeSH
• zákroky plastické chirurgie metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

• MeSH
• butyrofiliny * genetika   metabolismus   MeSH
• COVID-19 * genetika   komplikace   imunologie   virologie   MeSH
• dítě MeSH
• genetická predispozice k nemoci MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• SARS-CoV-2 * MeSH
• syndrom systémové zánětlivé reakce * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH