Familyal Hemofagositik Lenfohistiozisli Bir Olguda Yeni Birleşik Heterozigot Stxbp 2 Mutasyonu

Yıl 2017, Cilt: 11 Sayı: 3, 206 - 208, 01.08.2017

Ayşenur Bahadır Erol Erduran

Öz

Familyal veya primer hemofagositik lenfohistiositozis (FHLH) nadir görülen otozomal resesif geçişli genetik bir hastalıktır. FHLH genellikle infant döneminde tanı almakta, ateş, hepatosplenomegali, pansitopeni ve daha az sıklıkta santral sinir sistemi tutulumu ile karakterizedir. Hastalığın kesin tanısı hastalığa neden olan mutasyonun gösterilmesi ile konur. FHLH ile ilgili bilinen genetik mutasyonlar; perforin (PRF1; FHLH 2), UNC13D (FHLH 3), syntaxin 11 (STX11; FHLH 4), syntaxinbinding protein 2 (STXBP2; FHLH 5) ve bilinmeyen 9q21.3-q22 (FHLH 1) kromozomunda lokalize gen mutasyonlarıdır. STXBP2 (FHLH 5) mutasyonu infant döneminde sıklıkla gastroenterit sonrası görülen genellikle kötü seyirli bir HLH tipidir. Biz de kliniğimize akut hepatit tablosu ile başvuran ve HLH tanı kriterlerini sağlayan, HLH 2004 tedavi protokolü sonrası ishal ve SSS tutulum bulguları ile nüks izlenen altı aylık bir infantı yeni birleşik heterozigot STXBP2 mutasyonu saptanması nedeniyle sunduk.

Anahtar Kelimeler

Familyal hemofagositozis, İnfant, STXBP2 Arginin 235Prolin, STXBP2 İzolosin19 Treonin

A Novel Compound Heterozygous STxBP2 Mutation in a Case with Familial Hemophagocytic Lymphohistiocytosis

Öz

Familial or primary hemophagocytic lymphohistiocytosis (FHLH) is a rare genetic disease with autosomal recessive inheritance. FHLH is usually diagnosed during infancy and it is characterized by fever, hepatosplenomegaly, pancytopenia and less often involvement of the central nervous system. One of the diagnostic criteria is demonstrating a previously known mutation. Known gene mutations related to FHLH are perforin (PRF1; FHLH 2), UNC13D (FHLH 3), syntaxin 11 (STX11; FHLH 4), syntaxin-binding protein 2 (STXBP2; FHLH 5) and unknown gene mutations localized on chromosome 9q21.3-q22 (FHLH 1). The STXBP-2 (FHLH 5) mutation is a poor prognosis HLH type frequently seen in infants after gastroenteritis. We detected a novel compound heterozygous STXBP2 mutation in a six-month-old infant presenting with acute hepatitis and meeting the HLH diagnostic criteria and who developed reactivation with diarrhea and CNS involvement findings after the HLH 2004 treatment protocol was used

Anahtar Kelimeler

Familial hemophagocytosis, Infants, STXBP2 Arginine 235Proline, STXBP2 İzoleucine19 Threonine

Kaynakça

• Busiello R, Fimiani G, Miano M G, Arico M, Santoro A, Ursini M V, et al. A91V Perforin variation in healthy subjects and FHLH patients. Int J Immunogenet 2006; 33:123-5.
• zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G, et al. Mutations spectrum in children with primary hemophagocytic lymphohistiocytosis: Molecular and functional analyses of PRF 1, UNC 13D, STX11, and RAB27A. Hum Mutat 2006;27:62-8.
• Balta G, Okur H, Unal S, Yaralı N, Gunes A, Unal S, et al. Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation. Leuk Res 2010; 34:1012-7.
• Marsh R A, Satake N, Biroschok J, Jacobs T, Johnson T, Johnson J, et al. STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. Pediatr Blood Cancer 2010; 55:134-40.
• van Egmond ME, Vermeulen RJ, Peeters-Scholte CM, Augoustides-Savvopoulou P, Abbink F, Boelens JJ, et al. Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by brain magnetic resonance ımaging. Neuropediatrics 2011;42:191-3.
• Kaya Z, Bay A, Albayrak M, Kocak U, Yenicesu I, Gursel T. Prognostic factors and long-term outcome in 52 Turkish with hemophagocytic lymphohistiocytosis. Pediatr Crit Care Med 2015;16:165-73.
• Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009:127-31.
• Cohen JI, Niemela JE, Stoddard JL, Pittaluga S, Heslop H, Jaffe ES, et al. Late-onset severe chronic active EBV in a patient for five years with mutations in STXBP2(MUNC18-2) and PRF1(Perforin 1). J Clin Immunol 2015;35:445-8.
• Weitzman S. Approach to hemophagocytic syndromes. Hematology Am Soc Hematol Educ Program 2011;2011:178-83.
• Erduran E. Hemophagocytic lymphohistiocytosis. Turkiye Klinikleri J Pediatr Sci 2005;1:74-80.
• Gürgey A, Göğüş S, Ozyürek A, Aslan D, Gümrük F, Cetin M, et al. Primary hemophagocytic lymphohistiocytosis in Turkish children. Pediatr Hematol Oncol 2003;20:367-71.
• zur Stadt U, Rohr J, Seifert W, Koch F, Grieve S, Pagel J, et al. Familial haemophagocytic lymphohistiocytosis type 5 (FHL5) is caused by mutations in Munc 18-2 and impaired Binding to Syntaxin 11. Am J Hum Genet 2009;85:482-92.
• Cote M, Menager MM, Burgess A, Mahlaoui N, Picard C, Schaffner C, et al. Munc 18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. J Clin Invest 2009;119:3765-73.
• Nagai K, Yamamoto K, Fujiwara H, An J, Ochi T, Suemori K, et al. Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes. PLoS One 2010;5:e14173.
• Cetica V, Santoro A, Gilmour K C, Sieni E, Beutel K, Pende D, et al. STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. J Med Genet 2010;47:595-600.
• Pagel J, Beutel K, Lehmberg K, Koch F, Maul-Pavicic A, Rohlfs A K, et al. Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial haemophagocytic lymphohistiocytosis type 5 (FHL5). Blood 2012;119:6016-24.