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

Abstract

Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex and involves various gene mutations. Severe combined immunodeficiency (SCID), characterized by severe T-cell lymphocytopenia and a lack of antigen-specific T-cell and B-cell immune responses, is of seldom occurrence. In 10-15% of pediatric patients, SCID is caused by adenosine deaminase (ADA) deficiency. The authors describe the case of a boy who suffered from both aHUS and ADA-deficient SCID. At the age of 9 months, the patient presented acute kidney injury with anuria and coagulopathy. The diagnosis of aHUS was established on the basis of alternative complement pathway deregulation and disease-associated gene mutations. Further examination revealed immune system failure and, at the age of 13 months, the ADA deficiency was confirmed by genetic tests and the boy was diagnosed with ADA-SCID. ADA SCID has recently been described as a possible triggering factor of aHUS development and progression. However, more research is required in this field. Nevertheless, it is crucial in clinical practice to be aware of these two co-existing life-threatening diseases.

Keywords: adenosine deaminase deficiency; atypical hemolytic uremic syndrome; children; severe combined immunodeficiency; thrombotic microangiopathy.

Figure 1

Severe course of Varicella Zoster in the described case.

Figure 2

Small fibrin thrombi are visible in the interstitium (arrowheads).

Figure 3

Increased cellularity of the glomeruli, accompanied by extracellular matrix expansion. Small thrombi located in the interstitium (arrowheads). Small arteriole with a thick wall (arrow).

Figure 4

Electron microscopy findings in HUS. (A) Glomerular capillary separation of endothelial cells from the underlying glomerular capillary basement membrane (asterisks), markedly widened sub-endothelial space with fluffy-like material. Swelling of the capillary endothelial cells, electron lucent blebs are visible in the capilary lumen (#). Scale bar: 5 μm. (B) Higher magnification of a capillary wall; the arrows indicate the loss of endothelial fenestration, foot processes flattening, and microvilli on podocyte surface are also visible (arrowheads). Scale bar: 2 μm (C) Fragment of glomerular capillary wall with a widened sub-endothelial space and rich fluffy-like material under the endothelial cells. Capillary loop exhibits mild endothelial cell swelling with the absence of normal fenestra (#) Scale bar: 1 μm. (D) White box, magnification of (C) Endothelial cell contains a tubuloreticular inclusions (arrows). Moreover, flattening of podocyte foot processes also occurs (arrowhead). The presence of tubuloreticular inclusions (TRIs) in glomerular endothelial cells associated with viral infections (so-called interferon footprints) Scale bar: 500 nm.