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05-01-2012 | Genetics | Article

Primary immunodeficiency mortality varies by disease type

Abstract

Free abstract

MedWire News: The mortality rate among patients with primary immunodeficiency disorders (PID) varies according to the specific disorder and is highest among those with T- and B-cell severe combined immunodeficiencies, researchers report.

Furthermore, the mortality rate is higher among patients with a history of parental consanguinity, and among those who develop sepsis, and adenovirus and cytomegalovirus (CMV) infections, say Waleed Al-Herz and Mohamed Moussa from the University of Kuwait.

The researchers explain that "early diagnosis of PID is critical so life-saving treatment and precautions can be implemented."

Therefore, "understanding the factors accountable for mortality in this group of patients can help physicians to better monitor and manage the disease," they add.

Al-Herz and Moussa studied data for 176 patients with PID to identify variables associated with increased risk for death.

The patients had been diagnosed with combined T- and B-cell immunodeficiencies (30.1%), predominantly antibody immunodeficiencies (19.9%), other well-defined immunodeficiencies (25%), diseases of immune dysregulation (14.8%), congenital defects of phagocyte number, function, or both (6.3%), and complement deficiencies (4.0%). The mean age at onset of symptoms was 15 months, while the mean age at diagnosis was 43 months.

During 3.5 years of follow-up, 48 (27.3%) patients died, corresponding to a mortality incidence rate of 77.5 per 1000 person-years. The 2-, 4-, and 6-year survival rates after onset of symptoms were 76%, 73%, and 69%, respectively.

The researchers say that the mortality rate is higher than that observed in previous studies, which may be due to the high frequency of severe forms of PID (ie, combined T- and B-cell immunodeficiencies), and the fact that only 36% of patients were treated with hematopoietic stem cell transplantation.

As reported in the Journal of Clinical Immunology, mortality rates varied considerably among patients affected by different PID types. The death rate was highest among patients with combined T- and B-cell immunodeficiency (77.8%) and familial hemophagocytic lymphohistiocytosis (64.3%), and lowest among those with DiGeorge syndrome (4.5%).

Moreover, mortality rate varied within the same PID category. For example, among patients with combined T- and B-cell immunodeficiencies, 85.7% of those with RAG1 deficiency died, compared with 45.5% and 16.7% of those with MHC II and DOCK8 deficiencies, respectively.

"This confirms the previous observation that PID are a heterogeneous group of disorders," the researchers remark.

The most common cause of death was sepsis (46%), followed by pneumonia (29%).

Al-Herz and Moussa found that parental consanguinity, sepsis, adenovirus and CMV infections, failure to thrive, PID category, and onset age below 6 months were significant predictors for death. However, after adjustment for confounding between these variables, only parental consanguinity, sepsis, and adenovirus and CMV infections remained significant.

The researchers conclude: "Early diagnosis and aggressive therapeutic interventions specifically targeted to PID patients with early onset age of disease, CMV and adenovirus infections, and failure to thrive may help increase their chance of survival. In addition, the community should be educated about the possible health burdens of consanguineous marriages."

By Laura Dean

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