Atypical hemolytic-uremic syndrome in a patient with adenosine deaminase deficiency

Abstract

Inherited defects in the ubiquitous adenosine deaminase (ADA) enzyme disrupt the function of the immune system as well as many other organs and tissues. Some patients may also suffer from kidney damage. Here we report on an ADA-deficient patient who was treated with ADA replacement therapy from infancy and at 6 years of age developed acute kidney failure, thrombocytopenia, and severe anemia. A kidney biopsy demonstrated mesangiolysis and occlusion of kidney loops by erythrocytes and platelet aggregates, which is consistent with hemolytic-uremic syndrome (HUS). There was no evidence of exposure to Shiga toxins, nor were any complement abnormalities detected. The kidney function improved following hemodialysis. Our report demonstrates the increased susceptibility of ADA-deficient patients to develop HUS and expands the nonimmune abnormalities associated with ADA deficiency. This further emphasizes the vigilance required when caring for such patients. Statement of novelty:Here we provide the first detailed clinical and histological characterization of hemolyticuremic syndrome developing in an ADA-deficient patient.

Atypical Hemolytic Uremic Syndrome (aHUS) and Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)—Two Diseases That Exacerbate Each Other: Case Report

“…Such findings may impact the course of aHUS, accelerating the progress of renal failure and diminishing the clinical response to treatment. The findings of this case, together with the cases described in the cited references [4,25], suggest that ADA-SCID apart from aHUS may present with nephropathy during infancy, also owing to adenosine-mediated arterial and glomerular injury with concurrent hepatic injuries.…”

“…According to the literature, which is limited to case reports, the mechanism of ADA-SCID influencing aHUS development might be connected with infection, deregulation of complement function, autoimmunity, or impaired metabolism; however, no certain connections were established [4,25]. However, these reports cannot be taken as evidence that the reported cases did have thrombotic microangiopathy due to defective regulation of the alternative complement pathway, because genetic variants were not demonstrated.…”

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency

“…ADA deficiency has been associated preferentially with abnormalities in lymphoid development and function. [3][4][5][6][7][8][9][10] Additional defects with varied clinical significance and attributed to diverse mechanisms have been observed in myeloid cells [11][12][13] and the lungs, [14][15][16][17] brain, [18][19][20][21][22][23] skeleton, [24][25][26] liver, [27][28][29] and kidneys, [30][31][32] as has increased risk for tumor development (Table I). [33][34][35][36][37] ADA-associated abnormalities have been reviewed previously 1,38,39 and will not be detailed here.…”