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195 A NOVEL MUTATION IN THE SH2D1A GENE PRODUCING FATAL X-LINKED LYMPHOPROLIFERATIVE DISEASE.
  1. J. T. Hamrick,
  2. K. P. McRedmond,
  3. D. Amrol
  1. Department of Pediatrics, University of South Carolina, Columbia, SC

Abstract

A previously healthy 10-month-old boy was admitted with 1 week of fever, rash, and malaise. He appeared lethargic with a fever of 1028F and an elevated heart rate. He had a purpuric and petechial rash over his trunk and extremities and an erythematous bulging tympanic membrane note on the right. His liver was palpable 4 cm below the costal margin and he had no splenomegaly. His initial white blood cell count was 3.9 K/μL with 68% lymphocytes and 13% atypical lymphocytes. His hemoglobin was 8.1 mg/dL platelet count 36,000 K/μL. His liver enzymes and lactate dehydrogenase were all elevated. Epstein-Barr virus serology indicated acute infection. His immunoglobulins were all normal. He was treated with ceftriaxone for acute otitis media and possible bacteremia; over the next several days he improved clinically with less lethargy and improved appetite. However, his pancytopenia worsened necessitating red blood cell and platelet transfusions. His bilirubin and liver enzymes continued to increase. His triglycerides were slightly elevated and fibrinogen was decreased. A bone marrow biopsy revealed hypocellular marrow with no evidence of hemophagocytosis. He was treated with high-dose intravenous immunoglobulin, acyclovir, steroids, and chemotherapy. Three weeks into his illness he developed respiratory distress and was intubated. He developed progressive liver failure with coagulopathy and appeared septic. He passed away 24 days after the onset of his illness. Gene sequencing at the University of Washington identified a point mutation in exon 1 resulting in a new splice and the deletion of 22 base pairs, frame shift, and early termination of the SH2D1A confirming the diagnosis of XLP. His mother is a carrier for the mutation. His soluble interleukin-2 (sIL-2R) receptor level was 9311 U/mL and perforin studies were normal. Natural killer cell function was not able to be performed. XLP is a rare genetic disorder that usually affects previously healthy males in the first decade. The defective gene responsible for this disease encodes the protein SAP (signaling lymphocyte activation molecule or SLAM-associated protein, also called DSHP or SH2D1A). XLP can have a similar clinical picture to hemophagocytic lymphohistiocytosis and in series of HLH patients mutations in SAP are frequently found.

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