Primary Immunodeficiency Diseases Associated with Neurologic Manifestations

Abstract

Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders of the immune system, predisposing individuals to recurrent infections, allergy, autoimmunity, and malignancies. A considerable number of these conditions have been found to be also associated with neurologic signs and symptoms. These manifestations are considered core features of some immunodeficiency syndromes, such as ataxia-telangiectasia and purine nucleoside phosphorylase deficiency, or occur less prominently in some others. Diverse pathological mechanisms including defective responses to DNA damage, metabolic errors, and autoimmune phenomena have been associated with neurologic abnormalities; however, several issues remain to be elucidated. Greater awareness of these associated features and gaining a better understanding of the contributing mechanisms will lead to prompt diagnosis and treatment and possibly development of novel preventive and therapeutic strategies. In this review, we aim to provide a brief description of the clinical and genetic characteristics of PID associated with neurologic complications.

Mitochondria Are Gate-keepers of T Cell Function by Producing the ATP That Drives Purinergic Signaling

“…It is likely that purine salvage pathways are involved in these mechanisms (22). Several immune dysfunctions, including SCID, are caused by deficiencies of key enzymes involved in purine salvage pathways (35)(36)(37). However, it is also possible that de novo purine synthesis and creatine kinases are involved in the formation of ADP that can be phosphorylated and converted to ATP in mitochondria (21).…”

Important differences in the diagnostic spectrum of primary immunodeficiency in adults versus children

“…Ataxic gate and an increased serum level of a-feto protein are two important signs of combined immunodeficiency in children associated with ataxia-telangiectasia (AT), AT-like disease and RNF168 deficiency [11,56,57].…”

“…Cerebrospinal fluid test and imaging may reveal viral encephalitis in patients with a history of chronic infections due to defects in innate immunity including mutations in TLR3, UNC93B1, TRAF3, TRIF and TBK1 [56,60].…”

“…A diagnosis of cognitive impairment by a pediatric psychologist in patients with a phagocytosis defect, a neurological defect and amyelodysplastic syndrome may suggest the presence of Kostmann disease due to a mutation in the HAX1 gene [56,77,78].…”

A glance on recent progresses in diagnosis and treatment of primary immunodeficiencies/ Progrese recente în diagnosticul şi tratamentul imunodeficienţelor primare

“…However, it has to be stressed that for taking the correct actions the widely promulgated "warning signs" have to be interpreted by experts (21). Other tools to raise awareness might be medical discipline-specific reviews (22)(23)(24)(25)(26) or data mining in national or international registries. National registries may not have the power of international registries (http:// esid.org/Working-Parties/Registry/ESID-Online-Registry, accessed April 2014).…”