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Case Report
 

Severe Course of Community-Acquired Pneumonia in an Adult Patient Who Is Heterozygous for Q481P in the Perforin Gene: Are Carriers of the Mutation Free of Risk?
 

LA García-Astudillo,1 A Fontalba,2 F Mazorra,3 MJ Marín,1 A Castellanos,4 S Fernández,5 R Tejido,6 M López-Hoyos1

1 Immunology Division,University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain
2 Molecular Genetics Unit, University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain
3 Pathology Department, University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain
4 Intensive Care Department, University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain
5 Pneumology Service, University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain
6 UARH,University Hospital Marqués de Valdecilla-IFIMAV, Santander, Spain

J Investig Allergol Clin Immunol 2009; Vol. 19(4): 311-316
 

 Abstract


Most cases of autosomal recessive hemophagocytic lymphohistiocytosis (HLH) are associated with over 50 mutations in the perforin gene.
Some of these mutations have no clear functional association. Only homozygous patients display a full-blown syndrome, whereas no severe disease has been described in heterozygous carriers of these mutations despite the presence of functional and phenotypic alterations in cytotoxic cells. We study the family of a child who died from HLH at 6 months of age due to a Q481P mutation in the perforin gene. The study is particularly interesting because the patient’s heterozygous father experienced severe community-acquired pneumonia that could be attributed to deficient in vitro NK cell activity despite normal perforin expression. This case report suggests that impaired NK cell activity
in a heterozygote can result in poorer initial control of infections with severe clinical expression.

Key words: Hereditary hemophagocytic lymphohistiocytosis. NK cells. Perforin. Q481P.