RESUMO
BACKGROUND X-linked intellectual disabilities constitute a group of clinically and genetically heterogeneous disorders that are divided into syndromic and nonsyndromic forms. PAK3 mutations are associated with X-linked nonsyndromic forms of intellectual disability, with the most common clinical features being cognitive deficit, large ears, oral motor hypotonia, and neurobehavioral abnormalities. These mutations have been reported to be associated with either loss of the PAK3 protein or loss of its kinase activity. We report a case with the novel PAK3 variant c.685C>T p.(Pro229Ser), which has not been previously described. CASE REPORT We report the first case of a PAK3 mutation to present with the common clinical features along with immunodeficiency resembling common variable immune deficiency. Our patient was a 10-year-old girl who had experienced septic shock with a rapidly deteriorating course when she was 5-years-old. The initial immune work-up showed lymphopenia affecting all cell lines, but preferentially the B-cell compartment. Further work-up of this patient revealed low levels of immunoglobulin (Ig) G, undetectable IgA, reduced IgG1 and IgG2 subclasses, and poor response to the diphtheria/tetanus vaccine. Lymphocyte function, tested as the response to the mitogen phytohemagglutinin, was low and fluctuated between 9% and 22% compared with control samples. The patient experienced recurrent respiratory tract infections, and she responded well to regular intravenous Ig treatment and antibiotic prophylaxis. CONCLUSIONS The current case might provide a new insight into PAK3 gene function. Although further evidence is needed, it is worth considering that immunological abnormalities may be associated with PAK3 gene mutations.
