Genetic Test Finds aHUS in Pregnant Woman Hospitalized with Variety of Ills

José Lopes, PhD avatar

by José Lopes, PhD |

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aHUS, genetic testing

A pregnant woman who came to a hospital complaining of a variety of ills was diagnosed with atypical hemolytic uremic syndrome (aHUS) through genetic testing in a process described in a case report, and responded well to treatment with Soliris (eculizumab).

The case study, “Diagnosis of atypical HUS using Genetic Testing,” appeared in the journal Clinical Laboratory Science.

The 33-year-old woman was 31 weeks pregnant with twins (full gestation is 38 to 42 weeks) came she arrived at a hospital  emergency room in Texas with complaints of shortness of breath, headache, and blurry vision in the left eye. She had experienced significant edema (swelling) during her pregnancy, and a recent urinary tract infection. Her blood pressure was high (158/98 mmHg).

Blood analysis found a higher-than-usual white blood cell count and high levels of neutrophils, but a lower-than-normal amount of platelets and red blood cells. She also had a modest increase in fibrin degradation products, which result from blood clot degradation, as well as elevated blood urea nitrogen, creatinine and liver enzymes — alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase — indicating impaired liver function. A urine analysis revealed the presence of blood, white blood cells, protein, bacteria, and yeast.

Overall, these findings indicated hemolysis — red blood cell destruction — caused by thrombotic microangiopathies (TMAs), or damage to small blood vessels that activates the coagulation cascade, and which are characteristic of aHUS and other diseases.

Subsequent blood coagulation results ruled out antiphospholipid antibody syndrome and disseminated intravascular coagulation as causes for the patient’s TMAs. An assessment of the cardiac markers creatine kinase-muscle/brain fraction and troponin I showed a low likelihood of heart damage.

This finding, plus the woman’s testing negative for blurry vision and other vision disorders, further ruled out malignant hypertension as a possible cause of TMAs.

Reduced activity of the ADAMTS13 enzyme — involved in blood clotting — suggested the presence of thrombotic thrombocytopenic purpura (TTP), although these levels were not as low as in classical TTP, the scientists reported. The woman was started on plasma exchange therapy, but a satisfactory improvement in laboratory values within one week was not evident.

Negative results for the presence of Shiga toxins indicated that the patient’s hemolysis was not caused by HUS. An assessment of complement proteins — a set of more than 20 blood proteins that are part of the body’s immune defense — was done to investigate the possibility of aHUS showed normal results for both C3 and C4. This suggested that aHUS was unlikely.

Her persistently elevated blood urea nitrogen and creatinine indicated renal failure. A biopsy conducted on day 10 — a few days after giving birth — showed changes consistent with preeclampsia, characterized by high blood pressure and organ damage (most commonly in the liver and kidneys), with progression to TMA.

These findings made the clinicians at Tarleton State University think the woman most likely had HELLP syndrome. High levels of brain natriuretic peptide, a biomarker of cardiovascular diseases, “strongly supported our early suspicion that the patient was suffering from HELLP syndrome,” they wrote.

Still, they ordered an aHUS genetic susceptibility panel, which assesses gene variants associated with this disorder. It revealed a heterozygous (one gene copy) mutation, a deletion of the complement system genes CFHR1 and CFHR3, and the woman’s treatment was change to Soliris, Alexion’s anti-C5 antibody.

“The patient’s problems rapidly resolved, confirming aHUS as the cause of her troubles,” the team concluded.