A new case report described a baby with respiratory failure who was diagnosed with atypical hemolytic uremic syndrome (aHUS) after suspicion of Streptococcus pneumoniae (SPN)-induced HUS (pHUS).
The study, “A Case of Suspected Streptococcus Pneumoniae Hemolytic Uremic Syndrome (pHUS) with Utilization of Minor Crossmatching for Platelet Blood Products Lead to a Diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS),” was published in the journal Annals of Clinical & Laboratory Science.
In children, thrombotic microangiopathy — a group of syndromes that includes aHUS and is characterized by fragmented red cells, anemia, low levels of platelets and clots in small blood vessels — may result from an invasive infection with pneumococcal bacteria such as SPN. Ultimately, this may lead to pHUS with subsequent hemolysis — red blood cell destruction — and end-organ damage.
pHUS can be identified by minor blood crossmatch incompatibility — between a donor and a recipient — derived from agglutination of exposed T-antigens on the recipient’s red blood cells to anti-T antibodies in the plasma of donor blood products. Of note, a bacterial enzyme called neuraminidase is able to expose the T-antigen (called T-activation) — normally inaccessible due to spatial arrangement — in red blood cells, platelets, and other cell types to anti-T antibodies, prompting pHUS complications.
The team from The University of Texas Health Science Center at Houston described the case of a 6-month-old boy who presented with difficulty breathing and fever. About six hours prior to hospital admission, the patient’s mother noticed that he had worsening tachypnea (rapid breathing), which did not respond to an albuterol nebulizer. His twin had recovered from similar symptoms the week before.
The boy then showed lower-than-normal levels of glucose, sodium and creatinine — a marker of kidney function — among other alterations, as well as leukopenia — a low number of white blood cells. He was given the antibiotics Rocephin (ceftriaxone) and vancomycin, and transferred to the team’s pediatric intensive care unit.
Upon arrival, the boy was intubated for respiratory failure. Blood cultures positive for SPN, hemolytic anemia, low platelet count, and renal failure were subsequently observed. Based on the clinical presentation, the team suspected pHUS.
The pathologist requested a minor crossmatch with the boy’s red blood cells and platelets to determine whether significant T-activation was present.
The results revealed no agglutination, which made T-activation unlikely. Subsequent genetic tests showed heterozygous mutations (in one gene copy) in the C3 gene — implicated in the complement system, a set of more than 20 proteins that are part of the body’s immune defense; a variant in an intron — a DNA bit normally taken out during in protein production — of the PLG gene; a missense mutation — a change in the building blocks of DNA, called nucleotides, leading to a different amino acid — in DGKE; another variant in MCP/CD46 — previously linked with aHUS risk — and a deletion in CFHR1–CFHR3.
Together with the absence of the Shiga toxin and the normal levels of the enzyme ADAMTS13 — which ruled out HUS and thrombotic thrombocytopenic purpura, respectively — these findings resulted in a diagnosis of aHUS.
Overall, “given the limited availability of appropriate lectins/anti-sera to confirm T activation, utilization of a minor crossmatch should be considered in cases of suspected T activation,” the scientists stated.