Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

Alice D Chang,Deborah K Mccurdy,Kerry Gallagher,Raffi Tachdjian,Ora Yadin,E Richard Stiehm,Charles Lassman

doi:10.1080/17402520600877778

Alice D Chang, Deborah K Mccurdy + Show 5 more

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https://doi.org/10.1080/17402520600877778

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Abstract

We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

Highlights

DiGeorge syndrome (DGS), first described by Dr Angelo DiGeorge in 1965 (Cooper et al 1965), known as the 22q11 deletion syndrome, is associated with craniofacial, cardiac, thymic, immunologic, endocrine, and developmental abnormalities (Perez and Sullivan 2002)
We describe a patient with DGS who developed cryoglobulinemia and antiphospholipid syndrome (APS)
The cardiac history, absent thymus, and 22q11.2 microdeletion led to the diagnosis of DGS

Summary

Introduction

DiGeorge syndrome (DGS), first described by Dr Angelo DiGeorge in 1965 (Cooper et al 1965), known as the 22q11 deletion syndrome, is associated with craniofacial, cardiac, thymic, immunologic, endocrine, and developmental abnormalities (Perez and Sullivan 2002). Cryocrit was 1% on day 1 (normal: negative on day 4). Dilute Russell viper venom time (DRVVT) was borderline positive; cardiolipin IgM was 17 PLU (normal ,10); b2-glycoprotein I (b2GPI) IgM was 36 U/ml (normal ,10). The cryocrit resolved within 1 month of prednisone therapy; proteinuria resolved within 2 months After transient improvement, his fatigue progressed despite treatment with 1 g/day of mycophenolate mofetil (MMF). After 8 months, patient’s ACL IgM was 13 PLU, DRVVT was borderline positive, but b2GPI IgM became negative. This is a 14 year-old boy with partial DGS who developed APS, type III mixed cryoglobulinemia with DPGN, immune thrombocytopenia, MTHFR 677TT mutations, and pulmonic valve and LPA stenosis

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