Clinical Manifestation And Gene Analysis Of 3 Cases Of Pediatric Congenital Agammaglobulinemia With Concomitant Flaccid Paralysis

Objective: To investigate and analyze the clinical features and types of gene mutation in three patients from China with congenital agammaglobulinemia complicated with flaccid paralysis.Methods: Three patients diagnosed with congenital agammaglobulinemia complicated flaccid paralysis admitted to Children's Hospital of Chongqing Medical University from 2008 to 2016 were enrolled in this study.The clinical characteristics of the patients were summarized.The lymphocyte subsets were detected by flow cytometry.Mutations of BTK gene and ?HC gene were analysed by DNA sequencing.The ?HC transcripts were amplified by reverse transcription polymerase chain reaction(RT-PCR).Results: Congenital agammaglobulinemia was identified early as an immunodeficiency disease.However,there are few reports concerning flaccid paralysis in patients with congenital agammaglobulinemia.We describe the clinical features and gene mutations of 3 Chinese patients withcongenital agammaglobulinemia and concomitant flaccid paralysis.The average age of onset and diagnosis of these male patients(P1,P2,and P3)was 8.3 months and 5.6 years,respectively.Compared to patients with classic flaccid paralysis,manifestations were more moderate with slower progression of paralysis at the early phase.All patients received three times' OPV vaccinations before 6 months old,developing asymmetrical flaccid paralysis about 3-8 months after the third dosing of OPV.Decreased muscle strength,muscle tension,and limping were noted,but no cranial nerve paralysis or sensory disturbance.Siblings P1 and P2 had evident muscle atrophy,and electromyogram revealed nerve alterations in the unilateral lower limbs.No obvious abnormality were found about MRI manifestation of spinal cord.For P3,mycobacterium tuberculosis culture was positive in gastric juice and acid-fast bacillus was found in his pleural effusion,while the poliovirus culture was negative during the onset of his disease.In P1 and P2,missense mutation of Bruton's tyrosine kinase(BTK)gene(c.1559G>A)was identified.In P3,a compound heterozygous mutation of ?HC gene(170-175 insert C and 1956 G>A)was detected.Conclusion: Patients with congenital agammaglobulinemia after receiving OPV may occur flaccid paralysis.So we should attach importance to the early screening of the congenital agammaglobulinemia in newborns,guide the vaccination,and avoid vaccine-related diseases.