Ilke Taşkırdı, Turkey
S.B.U. Dr. Behcet Uz Children’s Education and Research Hospital Pediatric Immunology and AllergyPresenter of 2 Presentations
ATAXIA-TELANGIECTASIA IN A PATIENT PRESENTING WITH AUTOIMMUNITY AND HYPERIMMUNOGLOBULIN M SYNDROME
Abstract
Background and Aims
Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. Although elevated serum levels of IgM with decreased IgA and IgG levels have been reported in about 10% of the AT cases during their course of the disease, it is a rare finding at the onset and may cause to delay of diagnosis or misdiagnosis as hyper-IgM syndrome.
Methods
A 6-years-old boy referred our clinic due to hypogammaglobulinemia. He had been followed up with an autoimmune thrombocytopenia and hemolytic anemia at the age of 1.5 years. He was born to consanguineous parets and had history of recurrent sinopulmonary infections. Physical examination revealed growth retardation and mild gait disturbance.Serum IgG and IgA levels were low and IgM level was 519 mg/dl. CD19 lymphopenia was detected. AFP level was high and diagnosis of ataxia-telangiectasia was confirmed by detecting ATM homozygous mutation. The patient was treated with IVIG replacement, prophylactic antibiotic and antifungal.
Results
During the follow-up, neurological findings and telangiectasias progressively increased. The patient is still followed up without infection or hemolysis by IVIG replacement and prophylactic antibiotics.
Conclusions
Since cerebellar ataxia and ocular telangiectasia may not be present in infancy, the diagnosis of AT may be delayed during this period. Also the patients presenting with elevated IgM serum levels may be misdiagnosed as HIGM syndrome. As in this case, the diagnosis of AT should be kept in mind in patients with primary immune deficiency with abnormal neurological findings and autoimmunity.
TWO CASES OF CTLA 4 DEFICIENY WITH AUTOIMMUNE CYTOPENIA AND LYMPHOPROLIFERATION
Abstract
Background and Aims
CTLA-4 is an inhibitory receptor expressed on Treg cells. Haploinsufficiency of CTLA-4 cause severe loss of tolerance and autoimmune disease, hypogammaglobulinemia, recurrent infections, and lymphoproliferation.
Methods
Four years old girl, born to consanguineous parents (second-degree cousins) with a history of autoimmune cytopenia presented with reccurent sinopulmary infection, growth retardation and hepatomegaly. Coombs positive hemolytic anemia, polyclonal hypergammaglobulinemia and CD4 lymphopenia were detected. DNT cells and burst test were normal. The patient was treated with IVIG replacement, prophylactic antibiotic and antifungal. Autoimmune hemolytic anemia was improved with steroid treatment. The genetic analysis was sent but the patient died of infection. Nine years later CTLA 4 mutation was detected in the sent blood samples when CLTA4 mutation was defined in 2014.
Results
Nine years old male patient referred to our clinic due to lymphopenia with a history of dermatitis, recurrent lymphadenomegaly and autoimmune hemolytic anemia. Physical examination revealed bilateral inguinal lympadenomegaly and splenomegaly. Skin biopsy was compatible with psoriasiform spongiotic dermatitis. CD4 lymphopenia was detected but immunoglobulin levels and DNT were normal. Abdomen ultrasonography revealed splenomegaly and hypoechoic areas consistent with lymphoproliperative disease in the spleen. The patient was treated with IVIG replacement, prophylactic antibiotic and antifungal. Genetic analysis revealed CTLA 4 mutation.
Conclusions
CTLA4 mutations are characterized by immune dysregulation syndrome including extensive T cell infiltration in a number of organs, including the gut, lungs, bone marrow, central nervous system, and kidneys. CTLA 4 mutation should be considered in the differential diagnosis of immune dysregulation in patients with autoimmunity and lymphoproliferation.