Antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related to MTHFR gene C677T and A1298C heterozygous mutations in a young man with idiopathic hypoparathyroidism (DiGeorge syndrome)
ABSTRACT CONTEXT: Antiphospholipid syndrome (APS, or Hughes' syndrome) is a systemic autoimmune disorder characterized by antiphospholipid antibody positivity, which may lead to arterial and/or venous thrombosis. Hyperhomocysteinemia (HHcy), variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene point mutations, is also implicated in thromboembolic events. The association of APS and HHcy has already been described but has never been reported in patients with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome (22q11.2) in humans, whose phenotype conversely includes bleeding disorders. DATA ACQUISITION: In this report, we present the case of a 19-yr-old patient with a past medical history of learning disability and obesity affected with idiopathic hypoparathyroidism, metabolic syndrome, and diffuse vasculitis disorders. He was referred to our endocrinology clinic for the management of severe hypocalcemia. At the time of presentation he had been taking antiepileptic drugs for 2 wk and displayed facial dysmorphism (short neck, micrognathia, a small mouth, hypoplastic nasal alae, eye hypertelorism, and low-set simple ears). DGS was suspected and confirmed by both fluorescence in situ hybridization analysis and single nucleotide polymorphism-array analysis, which revealed contiguous gene microdeletion of the chromosome 22q11.2 in the minimal DiGeorge critical region, specifically at the gene locus D22S75 (N25). CONCLUSIONS: APS, revealed by anti-beta-2-glycoprotein and anti-prothrombin antibodies positivity, and moderate HHcy related to heterozygous C677T and A1298C point mutations of the MTHFR gene were identified as a possible cause of thrombotic disorder responsible for the widespread presence of cutaneous and cerebral lesions.
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- "Autoimmune disease in patients with DGS is relatively common. Our patient and the patient described by Nucera et al. (2006), demonstrate that DGS patients may develop systemic autoimmune disease of significant severity. Given the evidence for the infectious origins of aPL (Shoenfeld et al. 2006), recurrent infections in DGS in the background of compromised immunoregulation may predispose these patients to develop severe autoimmune complications such as APS and cryoglobulinemia. "
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 beta(2)-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.Clinical and Developmental Immunology 06/2006; 13(2-4):261-4. DOI:10.1080/17402520600877778 · 2.93 Impact Factor
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ABSTRACT: The occurrence of systemic lupus erythematosus (SLE) in several members of a family has spurred intense efforts to identify susceptibility genes predisposing to the disease. As a result, a number of candidate association genes in different ethnic groups have been identified, and some genes have been linked to specific lupus manifestations. Particularly where familial disease occurs in childhood, and especially when it occurs prior to puberty, complement deficiencies and other immunologic defects should be explored. Evidence of other forms of autoimmunity, including autoimmune thyroiditis and antiphospholipid syndrome (APS), is common in families with SLE. Familial APS is uncommon in the absence of other thrombophilic defects, but occasionally is seen with apparent autosomal dominant inheritance. Thus far, no firm gene associations have been identified for APS, in part because of the rarity of multiplex families to study. A search for other familial causes of thrombotic disease should be performed when APS occurs in more than one family member.Lupus 02/2007; 16(8):556-63. DOI:10.1177/0961203307078071 · 2.20 Impact Factor
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ABSTRACT: A 47-year-old woman with a recent clinical diagnosis of acute cholecystitis developed acute adrenal failure. Initial computed tomograms of the abdomen showed bilateral adrenal swelling which evolved into bilateral adrenal hemorrhage on repeat examination a few days later. Laboratory investigations revealed a previously undiagnosed primary antiphospholipid syndrome and homozygosity for the MTHFR C677T mutation with hyperhomocysteinemia. This case highlights the protean clinical manifestations of adrenal vascular accidents and the need for a thorough search for underlying prothrombotic states in this setting.Internal Medicine 12/2011; 50(23):2923-6. DOI:10.2169/internalmedicine.50.6342 · 0.90 Impact Factor