We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
SLCA29A3 gene defect in a patient with autoinflammatory disease and pure red blood cell aplasia: H syndrome.
- Authors
Ayvaz, Deniz Nazire Çağdaş; Tezcan, Ilhan; Köksal Özgül, Rıza; Özen, Seza
- Abstract
H Syndrome (HS) is an autosomal recessive (AR) genodermatosis associated with systemic findings caused by SLCA29A3 gene defect. SLC29A3 encodes a 475 aa protein named 'human intracellular equilibrative nucleoside transporter 3' which is localized in late endosomes/ lysosomes. This protein is thought to have role in transport of nucleotides/nucleobases/nucleotide analogs from lysosomal membrane and inner mitochondrial membrane to cytoplasm, maintaining a cytoplasmic pool for several cellular pathways. Here, a male patient having pure red cell aplasia (PRCA), articular deformities is presented. He was given the diagnosis of H Syndrome at the age of 26 years with whole-exome-analysis. A 22-year-old male patient, who was the fourth child of first-degree cousin parents referred to Immunology department for possible primary immunodeficiency (PID). After the age of 1.5 years, progressive articular deformities in small joints developed, and he started to take weekly erythrocyte transfusion for severe anemia due to PRCA. He had been operated for foot deformities. He had a history of a male sibling death. His elder brother had similar clinical findings, died at the age of 12 with renal failure. On physical examination he had vitiligo, cutaneous fungal skin lesions on feet, severe sensorineural hearing loss, had severe contractures/deformities in hands and feet. He had severe anemia. Immunologic test results showed lymphopenia, mildly low lymphocyte proliferation compared with healthy control. Acute phase reactants were elevated, and immunosuppressive therapies given before were not sufficient to control the progression of disease. In the follow-up, anti-GAD, anti-islet-cell, anti-TPO antibodies were found to be positive, given the diagnosis of diabetes mellitus. Biopsy taken from mesenteric lymphadenopathy was compatible with fungal infection. After intravenous immunoglobulin (IVIG) therapy was started, hematologic findings resolved, he had no further erythrocyte transfusion need, and progression of articular deformities stopped. As there is a consanguineous pedigree, sibling death history, whole-exome-analysis was performed for possible PID associated with autoimmunity. SLCA29A3 gene defect (c.1394 C>G; p.Ser465) was found. Now, he is fine, on monthly intravenous immunoglobulin therapy and low dose steroids (0.15 mg/kg). Several clinical findings; hyperpigmentation, hypertrichosis, hepatosplenomegaly, deafness, heart anomalies, hypogonadism, short stature, hyperglycemia/diabetes mellitus, hallux valgus/flexion contractures may be present in HS. Hyperpigmentation, hypertricosis defined in most of HS patients were not present in present patient. Vitiligo was not reported in HS before. IVIG therapy was useful with possible immunomodulatory effects in disease progression and resolution of hematologic findings. Whole-exome-analysis was useful to reveal the genetic defect in this very rare AR syndrome.
- Subjects
PURE red cell aplasia; SYNDROMES; NUCLEOTIDES; MITOCHONDRIAL membranes; CYTOPLASM
- Publication
Turkish Journal of Immunology, 2016, Vol 4, p54
- ISSN
1301-109X
- Publication type
Article