title: Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis.
abstract: Oral polio vaccine (OPV) has been used safely and efficiently for more than 40 years in preventive medicine. Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of OPV due to reversion of the vaccine strain virus to a neurovirulent strain. VAPP can occur in healthy recipients or their close contacts. However, persons with primary humoral immunodeficiencies are at a much higher risk. X-linked agammaglobulinemia (XLA) is a prototypic humoral deficiency caused by mutations in the Bruton's tyrosine kinase (BTK) gene. In addition to susceptibility to bacterial infections, patients with XLA are especially prone to enteroviruses. Here, we describe the occurrence of VAPP in a 15-month old Iranian boy. The child had received four doses of OPV, administered at birth, 2, 4, and 6 months of age. The patient's infectious history was unremarkable. Laboratory evaluation revealed low levels of immunoglobulin G and CD19(+) B cells of less than 1% of the lymphocyte population. A novel insertion (c.685_686insTTAC) in the SH3 domain of the BTK gene was detected as the underlying cause. Immunodeficient recipients of OPV can excrete poliovirus vaccine strains for a long period and are at risk of developing flaccid paralysis. They could also serve as a source of reverted virulent poliovirus to be reintroduced into the general population. This patient presented for the first time with VAPP, without any history of other major infections in 15 months. This suggests that a negative history for recurrent infections does not exclude the presence of a primary defect in the immune system.
authors.affiliation: Department of Pediatrics, Infectious Disease Research Center, Children's Medical Center, Medical Sciences/University of Tehran, Tehran, Iran.
authors.forename: Setareh
authors.initials: S
authors.lastname: Mamishi
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahmahmoudi
authors.forename: Hamideh
authors.initials: H
authors.lastname: Tabatabaie
authors.forename: Shahram
authors.initials: S
authors.lastname: Teimourian
authors.forename: Babak
authors.initials: B
authors.lastname: Pourakbari
authors.forename: Yousof
authors.initials: Y
authors.lastname: Gheisari
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yeganeh
authors.forename: Ali
authors.initials: A
authors.lastname: Salavati
authors.forename: Abdol-Reza
authors.initials: AR
authors.lastname: Esteghamati
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Gooya
authors.forename: Rakhshandeh
authors.initials: R
authors.lastname: Nategh
authors.forename: Nima
authors.initials: N
authors.lastname: Parvaneh
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010243:Paralysis / Q000209:etiology*; D017354:Point Mutation / Q000235:genetics*; D011051:Poliomyelitis / Q000209:etiology*; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D011055:Poliovirus Vaccine, Oral; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human