Background and Aims

DNA repair defects are rare, hereditary diseases with heterogenous manifestations but sharing clinical features as immune deficiency, cancer predisposition, growth retardation, neurological disorders.

Methods

We present four patients; two pairs of siblings, with Bloom and Nijmegen Breakage Syndrome.

Results

P1F1:18-year-old boy product to consangenious parents, had growth retardation and recurring otitis. Telangiectasies, typical facies and high sister chromatid exchanges suggested Bloom. He had hypogammaglobulinemia, absent polysaccharide antibody responses. Surgically removed upper right abdominal mass at age 4 was found to be Wilms tumor. He received chemotherapy for stage I, achieved complete remission without drug toxicity or relapse.

P2F1:12-year-old girl had growth retardation, recurring upper respiratory tract infections, cafe-au-lait spots on trunk, a giant nevus on her leg. She had hypogammaglobulinemia and received IVIG, antibacterial, antifungal prophylaxis, infections/year decreased on follow-up. She has not developed malignancy.

P1F2:9-year-old girl product to nonconsanguineous parents, was born with microcephaly, anal atresia, rectovaginal fistula and left ectopic pelvicaliectatic kidney. By age 9, along with dysmorphic findings, she had hepatosplenomegaly and mediastinal lymph nodes. She received rapamycine treatment for lymphoproliferation with partial response. Liver biopsy showed lymphoid infiltration but not lymphoma. She was started on IVIG and antibacterial prophylaxis.

P2F2:Patient was born at 28 weeks of gestation, weighing 1400 gr with microcephaly. At age 5, he had mild hypogammaglobulinemia and B-cell lymphopenia. Whole exome sequencing was performed for both siblings, revealing a homozygous mutation in NBS1 gene (del657_661).

Conclusions

Patients should be carefully evaluated for expected malignancies in case of primary immune deficiencies, especially under the category of DNA repair defects.

Background and Aims

Carriers of X-CGD have two populations of neutrophils resulting in a mosaic pattern in respiratory burst testing. There are increasing reports on photosensitivity, discoid lupus and autoimmunity in female carriers.

Methods

We present SLE and other autoimmune manifestations in 5 female-carriers in family of an index patient with X-CGD.

Results

Case-1:Patient’s mother, 32years-old, diagnosed with SLE for 11years. She had a history of deep venous thrombosis(DVT) at age of 11, and second DVT in her left leg during her pregnancy at 21years. She was tested for antiphosfolipid syndrome, Sjögren and SLE. She developed discoid lesions on face at age 29. For the last 3 years, her only symptom is a photosensitive rash on face. Anticardiolipin IgM/IgG are positive, ANA and anti-dsDNA are negative.

Case-2:Patient’s grandmother, 59years-old, has swelling and joint pain in fingers and toes for 3 years, diagnosed with rheumatoid arthritis and SLE.

Case-3:Patient’s aunt, 24years-old, diagnosed with SLE for 7years. She had multiple hospital admissions for joint pain, thrombocytopenia. She has recurring aphtous stomatitis and discoid rash. Laboratory testing showed she had 3+ANA, positive anti-histone antibodies, anti dsDNA and nucleosome.

Case-4:Patient’s aunt, 18years-old, diagnosed with SLE. She was first hospitalized at age 9 for recurrent arthritis. At age 17, she had pain, ecchymosis, swelling in leg with DVT. Recently, her renal biopsy revealed 2^nddegree lupus nephritis. ANA and anticardiolipin antibodies are positive.

Conclusions

Maternal female members of X-linkedCGD patients should be tested for carrier status and monitored for autoimmune diseases. Genetic counselling and consultation with rheumatology for autoimmune manifestations is required.