BACKGROUND: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. METHODS: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score <-2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. FINDINGS: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3-61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76-8·34; log-rank test p=0·0041). Patients who were underweight during age 1-3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26-17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. INTERPRETATION: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies. FUNDING: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.

• MeSH
• biologické markery analýza   MeSH
• dítě MeSH
• dospělí MeSH
• duševní poruchy etiologie   patologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní agentury MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• následné studie MeSH
• nemoci svalů etiologie   patologie   MeSH
• neurovývojové poruchy etiologie   patologie   MeSH
• předškolní dítě MeSH
• přenašeče monokarboxylových kyselin nedostatek   genetika   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• symportéry nedostatek   genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec 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
• multicentrická studie MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. METHODS: The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. RESULTS: The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. CONCLUSION: The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.

• MeSH
• dědičné zánětlivé autoimunitní nemoci komplikace   diagnóza   MeSH
• dítě MeSH
• dospělí MeSH
• familiární středomořská horečka komplikace   diagnóza   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nedostatek mevalonátkinázy komplikace   diagnóza   MeSH
• odchylka pozorovatele MeSH
• periodické syndromy asociované s kryopyrinem komplikace   diagnóza   MeSH
• počítačová simulace MeSH
• registrace MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency. METHODS: We developed the ADDI by consensus building. The top 40 enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions, which were then formally weighted in a scoring system derived using decision-making software, known as 1000minds. RESULTS: More than 80% of the experts and patients completed the online surveys. The preliminary ADDI contains 18 items, categorised in the following eight organ systems: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example, chronic musculoskeletal pain. CONCLUSIONS: An instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building. Patients fulfilled a significant role in this process.

• MeSH
• dědičné zánětlivé autoimunitní nemoci komplikace   MeSH
• dítě MeSH
• dospělí MeSH
• horečka komplikace   MeSH
• konsensus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• přehledová literatura jako téma MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH

Good syndrome (GS) or thymoma-associated immunodeficiency, is a rare condition that has only been studied in retrospective case series. General consensus was that GS has a worse prognosis than other humoral immunodeficiencies. In this study, physicians of GS patients completed two questionnaires with a two year interval with data on 47 patients, 499 patient years in total. Results on epidemiology, disease characteristics, and outcome are presented. Mean age at diagnosis was 60years and median follow-up from onset of symptoms was 9years. There was a high frequency of respiratory tract infections due to encapsulated bacteria. Median survival was 14years. Survival was reduced compared to age-matched population controls (5-year survival: 82% versus 95%, p=0.008). In this cohort survival was not associated with gender (HR 0.9, 95% CI 0.3-3.0), autoimmune diseases (HR 2.9, 95% CI 0.8-10.1) or immunosuppressive use (HR 0.3, 95% CI: 0.1-1.2).

• MeSH
• autoimunitní nemoci diagnostické zobrazování   epidemiologie   MeSH
• dítě MeSH
• infekce epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory brzlíku diagnostické zobrazování   epidemiologie   MeSH
• prognóza MeSH
• průzkumy a dotazníky MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syndromy imunologické nedostatečnosti diagnostické zobrazování   epidemiologie   MeSH
• thymom diagnostické zobrazování   epidemiologie   MeSH
• Check Tag
• dítě MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH