Deficiencia adenozín-deaminázy 2. typu (DADA2) je autoinflamačné ochorenie, ktoré bolo identifikované v roku 2014 ako monogénová príčina systémovej vaskulitídy charakteru polyarteritis nodosa, s prejavom febrilít, livedo racemosa, periférnych nekróz a skorého vzniku cievnych mozgových príhod. Za ostatných 10 rokov sa poznanie o fenotypovom spektre DADA2 značne rozšírilo. 378 prípadov doposiaľ publikovaných v svetovej literatúre radí DADA2 k zriedkavým ochoreniam, ale reprezentujú iba zlomok z celosvetovo odhadovaných 35 000 postihnutých jedincov (odhadovaná prevalencia ~ 1 : 222 000). Predstavujeme kazuistiky prvých 3 slovenských pacientov s geneticky aj laboratórne potvrdeným ochorením DADA2. Ilustrujú 3 krajné fenotypy tejto choroby – inflamatórne-vaskulopatický, imunodeficientný a hematologický, ktoré sa v niektorých charakteristikách prelínajú. Naša skúsenosť potvrdzuje nutnosť interdisciplinárnej starostlivosti a multimodálnej liečby tohto ochorenia. Vzhľadom na veľmi heterogénny klinický obraz je dôležité zvyšovať povedomie o DADA2, keďže aj v našej populácii je možné predpokladať výskyt doposiaľ nediagnostikovaných pacientov.

Deficiency of adenosine deaminase type 2 (DADA2) is an autoinflammatory disease identified in 2014 as a monogenic cause of systemic vasculitis resembling polyarteritis nodosa, with fever, livedo racemosa, peripheral necrosis, and early-onset stroke. Over the past 10 years, the knowledge of the phenotypic spectrum of DADA2 has expanded considerably. With 378 cases published so far in the world literature, DADA2 is considered a rare disease, but known cases represent only a fraction of the estimated 35,000 affected individuals worldwide (estimated prevalence ~ 1:222 000). We present the first 3 Slovak patients with genetically and biochemically confirmed DADA2. They illustrate 3 very distinct phenotypes of this disease - inflammatory-vasculopathic, immunodeficient and haematological that overlap in some characteristics. Our experience confirms the need for interdisciplinary care and multimodal treatment of this disease. Given the very heterogeneous clinical picture, it is important to raise awareness of DADA2, as more undiagnosed patients can be expected in our population.

• Klíčová slova
• deficiency of adenosine deaminase type 2 (DADA2),
• MeSH
• adenosindeaminasa genetika   MeSH
• dědičné zánětlivé autoimunitní nemoci * diagnóza   farmakoterapie   genetika   MeSH
• imunosupresivní léčba metody   MeSH
• inhibitory TNF aplikace a dávkování   terapeutické užití   MeSH
• kojenec MeSH
• lidé MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• předškolní dítě MeSH
• syndromy imunologické nedostatečnosti MeSH
• transplantace hematopoetických kmenových buněk metody   škodlivé účinky   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. OBJECTIVES: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. RESULTS: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. CONCLUSIONS: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.

• MeSH
• 1-fosfatidylinositol-3-kinasa * genetika   MeSH
• antigen CTLA-4 genetika   MeSH
• fosfatidylinositol-3-kinasy třídy I MeSH
• fosfatidylinositol-3-kinasy genetika   MeSH
• lidé MeSH
• mutace MeSH
• primární imunodeficience * genetika   MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• exom * genetika   MeSH
• genom lidský MeSH
• imunita * genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mutační analýza DNA * metody   MeSH
• novorozenec MeSH
• novorozenecký screening MeSH
• sekvenování exomu * metody   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• přehledy MeSH