Diferent clinical and laboratory evolutions in ataxia-telangiectasia syndrome: report of four cases

Abstract

We report four patients with ataxia-telangiectasia syndrome that presented varied neurologic evolution. Three patients initially presented neurologic alterations of slow progression, evolving to late immunocompromised conditions. The fourth patient presented, from symptom onset, immune and neurologic debilitation, that were both severe and of fast progression. The chronological sequence of the most commonly observed immunocompromised conditions were in our patients, in ascending order, IgA deficiency, IgG2 deficiency and the neutrophil phagocytosis stage and common variable immunodeficiency. The first two reports are of sisters in whom the diagnosis was done between the ages of three and six years, having ocular apraxia, cerebellar ataxia and telangiectasia. Slow progression of neurologic debilitation was observed, without presentation of intermittent infections. The patients began presenting accentuated immunocompromised conditions at the ages of 14 and 17 years, dying at the ages of 16 and 20 years, respectively, due to severe infections that were resistant to treatment. The diagnosis of the third case was established when the patient was two years old, presenting ataxia and telangiectasia. Syndrome progression was slow, presenting at the age of eight years more accentuated neurologic disorders and IgA deficiency. The fourth case presented significant neurologic compromise at the age of five, simultaneous to IgA and IgG2 deficiency, and repeating pneumonias and sinusitis. At this time, intravenous gammaglobulin reposition was done. The neurologic and immune disorders progressed rapidly, and at the age of eight presented the inability to walk. At this time inversion of the CD4/CD8 ration was verified through laboratory tests.

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

“…Furthermore, the observed RAB33A deficit would direct LDCV trafficking away from secretion towards autophago-lysosome degradation, and indeed elevated autophagy was documented by the high abundance of DEPTOR, SQSTM1, HSPB8 and BAG3 (Nivon et al, 2016), contrasting with lowered UBQLN2 and SLC2A1 abundance presumably via autophagic degradation (Cheng et al, 2020). In view of these observations, it is conceivable that abnormal phagocytosis of microbes or their components, such as zymosan, makes a relevant contribution to the immune deficit of A-T patients, as reported for 4 A-T cases (Forte et al, 2005). Further evidence for deficient trans-Golgi to endosome trafficking can be found in the proteome profile of ATM-kd neuroblastoma cells, where the endosomal anterior pole migration factor ASTN2 and the endocytosis AP3B2 (β-NAP) adaptor protein subunit abundance was substantially diminished, accompanied by a parallel reduction of ATM/ATR specific phosphorylation of AP1AR regulatory protein.…”