A 9month-old-boy with atypical hemophagocytic lymphohistiocytosis
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Keywords
Anemia, Neutropenia, , thrombocytopenia, hyperfeeeritinemia, Haemophagocytic lymphohistiocytosis
Abstract
Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes. Often, Hemophagocytic lymphohistiocytosis is an acquired syndrome. We report a case of a 9 month-old-boy presented with hepatosplenomegaly, severe anemia requiring repeated transfusions, thrombocytopenia, hypertriglyceridemia and very high hyperferritinemia. These clinical features of Hemophagocytic lymphohistiocytosis prompted a wide infectious and auto-immune request to be performed. After a wide diagnostic workup, he was referred to the immune hematologic unit, for hemophagocytic lymphohistiocytosis suspicion with unknown cause.
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References
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2. Mehta RS, Smith RE Hemophagocytic lymphohistiocytosis (HLH): a review of literature. Med Oncol 2013; 30(4):740. https://link.springer.com/article/10.1007%2Fs12032-013-0740-3
3. Imashuku S, Ueda I, Teramura T, Mori K, Morimoto A, Sako M, Ishii E. Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients. Eur J Pediatr 2005; 164 (5): 315–19. https://link.springer.com/article/10.1007%2Fs00431-005-1636-9
4. Janka G.E. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007; 166 (2):95–109 https://link.springer.com/article/10.1007%2Fs00431-006-0258-1
5. Parenti G, Sebastio G, Strisciuglio P, Incerti B, Pecoraro C, Terracciano L, Andria G. Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J. Pediatr 1995; 126 (2):246–51. http://www.sciencedirect.com/science/article/pii/S002234769570552X?showall%3Dtrue
6. Duval M, Fenneteau O, Doireau V, Faye A, Emilie D, Yotnda P, Drapier JC, Schlegel N, Sterkers G, de Baulny HO, Vilmer E. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr 1999; 134 (2):236-9. http://www.jpeds.com/article/S0022-3476(99)70423-3/fulltext
7. Tanner L.M, Nanto-Salonen K, Niinikoski H, Jahnukainen T, Keskinen P, Saha H, Kananen K, Helanterä A, Metso M, Linnanvuo M, Huoponen K, Simell O. Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance. J. Pediatr 2007; 150 (6):631–34. http://www.jpeds.com/article/S0022-3476(07)00118-7/fulltext
8. Güzel-Ozantürk A, Ozgül RK, Unal O, Hi?mi B, Ayd?n H?, Sivri S, Tokatl? A, Co?kun T, Aksöz E, Dursun A. Molecular and clinical evaluation of Turkish patients with lysinuric protein intolerance. Gene 2013;521 (2): 293–5. http://www.sciencedirect.com/science/article/pii/S0378111913002679
9. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol 2010; 6 (1): 137–54. https://www.ncbi.nlm.nih.gov/pubmed/20383897
10. Shinsaku I. Hyperferritinemia in Hemophagocytic Lymphohistiocytosis and Related Diseases. Pediatr Blood Cancer 2008; 51 (3):442–6 https://www.ncbi.nlm.nih.gov/pubmed/18506755
11. Aricò M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G, Martinetti M, Rusca MP. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996; 10(2):197-203. https://www.ncbi.nlm.nih.gov/pubmed/8637226
12. Ogier de Baulny H, Schiff M, Dionisi-Vici C. Lysinuric protein intolerance (LPI): A multi organ disease by far more complex than a classic urea cycle disorder. Molecular Genetics and Metabolism 2012; 106 (1):12–7 http://www.mgmjournal.com/article/S1096-7192(12)00035-2/fulltext
13. Sebastio G, Sperandeo MP, Andria G. Lysinuric protein intolerance: reviewing concepts on a multisystem disease. Am J Med Genet C Semin Med Genet 2011; 157C(1):54-62 https://www.ncbi.nlm.nih.gov/pubmed/21308987
14. Maines E, Comberiati P, Piacentini GL, Boner AL, Peroni DG. Lysinuric protein intolerance can be misdiagnosed as food protein-induced enterocolitis syndrome. Pediatric Allergy and Immunology 2013; 24: 509–510 https://www.ncbi.nlm.nih.gov/pubmed/23772603
15. Posey JE, Burrage LC, Miller MJ, Liu P, Hardison MT, Elsea SH, Sun Q, Yang Y, Willis AS, Schlesinger AE, Bacino CA, Lee BH. Lysinuric Protein Intolerance Presenting with Multiple Fractures. Mol Genet Metab Rep 2014; 1: 176–183 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235665/
16. Barilli A, Rotoli BM, Visigalli R, Bussolati O, Gazzola GC,Gatti R, Dionisi-Vici C, Martinelli D, Goffredo BM, Font-Llitjós M, Mariani F, Luisetti M, Dall'Asta V. Impaired phagocytosis in macrophages from patients affected by lysinuric protein intolerance. Mol Genet Metab 2012; 105(4):585-9 https://www.ncbi.nlm.nih.gov/pubmed/22325938
17. Barilli A, Rotoli B.M, Visigalli R, Bussolati O, Gazzola G.C, Kadija Z, Rodi G, Mariani F, Ruzza ML, Luisetti M, Dall'Asta V. In lysinuric protein intolerance system y+L activity is defective in monocytes and in GM-CSF-differentiated macrophages. Orphanet J Rare Dis 2010; 5:32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999609/
18. Tanner LM, Niinikoski H, Näntö-Salonen K, Simell O. Combined hyperlipidemia in patients with lysinuric protein intolerance. J Inherit Metab Dis 2010; 33 Suppl 3:S145-50. https://link.springer.com/article/10.1007%2Fs10545-010-9050-5
19. Lukkarinen M, Nanto-Salonen K, Pulkki K, Aalto M, Simel O. Oral Supplementation Corrects Plasma Lysine Concentrations in Lysinuric Protein Intolerance. Metabolism 2003; 52(7): 935-8. https://www.ncbi.nlm.nih.gov/pubmed/12870174
20. Mauhin W, Habarou F, Gobin S, Servais A, Brassier A, Grisel C, Roda C, Pinto G, Moshous D, Ghalim F, Krug P, Deltour N, Pontoizeau C, Dubois S, Assoun M, Galmiche L, Bonnefont JP, Ottolenghi C, de Blic J, Arnoux JB, de Lonlay P. Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood. Orphanet J Rare Dis. 2017; 12(1):3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217205/
1. Gholam C, Grigoriadou S, Gilmour K.C, Gaspar H.B. Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management. Clinical and Experimental Immunology 2011; 163: 271–83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048610/
2. Mehta RS, Smith RE Hemophagocytic lymphohistiocytosis (HLH): a review of literature. Med Oncol 2013; 30(4):740. https://link.springer.com/article/10.1007%2Fs12032-013-0740-3
3. Imashuku S, Ueda I, Teramura T, Mori K, Morimoto A, Sako M, Ishii E. Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients. Eur J Pediatr 2005; 164 (5): 315–19. https://link.springer.com/article/10.1007%2Fs00431-005-1636-9
4. Janka G.E. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007; 166 (2):95–109 https://link.springer.com/article/10.1007%2Fs00431-006-0258-1
5. Parenti G, Sebastio G, Strisciuglio P, Incerti B, Pecoraro C, Terracciano L, Andria G. Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J. Pediatr 1995; 126 (2):246–51. http://www.sciencedirect.com/science/article/pii/S002234769570552X?showall%3Dtrue
6. Duval M, Fenneteau O, Doireau V, Faye A, Emilie D, Yotnda P, Drapier JC, Schlegel N, Sterkers G, de Baulny HO, Vilmer E. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr 1999; 134 (2):236-9. http://www.jpeds.com/article/S0022-3476(99)70423-3/fulltext
7. Tanner L.M, Nanto-Salonen K, Niinikoski H, Jahnukainen T, Keskinen P, Saha H, Kananen K, Helanterä A, Metso M, Linnanvuo M, Huoponen K, Simell O. Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance. J. Pediatr 2007; 150 (6):631–34. http://www.jpeds.com/article/S0022-3476(07)00118-7/fulltext
8. Güzel-Ozantürk A, Ozgül RK, Unal O, Hi?mi B, Ayd?n H?, Sivri S, Tokatl? A, Co?kun T, Aksöz E, Dursun A. Molecular and clinical evaluation of Turkish patients with lysinuric protein intolerance. Gene 2013;521 (2): 293–5. http://www.sciencedirect.com/science/article/pii/S0378111913002679
9. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol 2010; 6 (1): 137–54. https://www.ncbi.nlm.nih.gov/pubmed/20383897
10. Shinsaku I. Hyperferritinemia in Hemophagocytic Lymphohistiocytosis and Related Diseases. Pediatr Blood Cancer 2008; 51 (3):442–6 https://www.ncbi.nlm.nih.gov/pubmed/18506755
11. Aricò M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G, Martinetti M, Rusca MP. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996; 10(2):197-203. https://www.ncbi.nlm.nih.gov/pubmed/8637226
12. Ogier de Baulny H, Schiff M, Dionisi-Vici C. Lysinuric protein intolerance (LPI): A multi organ disease by far more complex than a classic urea cycle disorder. Molecular Genetics and Metabolism 2012; 106 (1):12–7 http://www.mgmjournal.com/article/S1096-7192(12)00035-2/fulltext
13. Sebastio G, Sperandeo MP, Andria G. Lysinuric protein intolerance: reviewing concepts on a multisystem disease. Am J Med Genet C Semin Med Genet 2011; 157C(1):54-62 https://www.ncbi.nlm.nih.gov/pubmed/21308987
14. Maines E, Comberiati P, Piacentini GL, Boner AL, Peroni DG. Lysinuric protein intolerance can be misdiagnosed as food protein-induced enterocolitis syndrome. Pediatric Allergy and Immunology 2013; 24: 509–510 https://www.ncbi.nlm.nih.gov/pubmed/23772603
15. Posey JE, Burrage LC, Miller MJ, Liu P, Hardison MT, Elsea SH, Sun Q, Yang Y, Willis AS, Schlesinger AE, Bacino CA, Lee BH. Lysinuric Protein Intolerance Presenting with Multiple Fractures. Mol Genet Metab Rep 2014; 1: 176–183 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235665/
16. Barilli A, Rotoli BM, Visigalli R, Bussolati O, Gazzola GC,Gatti R, Dionisi-Vici C, Martinelli D, Goffredo BM, Font-Llitjós M, Mariani F, Luisetti M, Dall'Asta V. Impaired phagocytosis in macrophages from patients affected by lysinuric protein intolerance. Mol Genet Metab 2012; 105(4):585-9 https://www.ncbi.nlm.nih.gov/pubmed/22325938
17. Barilli A, Rotoli B.M, Visigalli R, Bussolati O, Gazzola G.C, Kadija Z, Rodi G, Mariani F, Ruzza ML, Luisetti M, Dall'Asta V. In lysinuric protein intolerance system y+L activity is defective in monocytes and in GM-CSF-differentiated macrophages. Orphanet J Rare Dis 2010; 5:32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999609/
18. Tanner LM, Niinikoski H, Näntö-Salonen K, Simell O. Combined hyperlipidemia in patients with lysinuric protein intolerance. J Inherit Metab Dis 2010; 33 Suppl 3:S145-50. https://link.springer.com/article/10.1007%2Fs10545-010-9050-5
19. Lukkarinen M, Nanto-Salonen K, Pulkki K, Aalto M, Simel O. Oral Supplementation Corrects Plasma Lysine Concentrations in Lysinuric Protein Intolerance. Metabolism 2003; 52(7): 935-8. https://www.ncbi.nlm.nih.gov/pubmed/12870174
20. Mauhin W, Habarou F, Gobin S, Servais A, Brassier A, Grisel C, Roda C, Pinto G, Moshous D, Ghalim F, Krug P, Deltour N, Pontoizeau C, Dubois S, Assoun M, Galmiche L, Bonnefont JP, Ottolenghi C, de Blic J, Arnoux JB, de Lonlay P. Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood. Orphanet J Rare Dis. 2017; 12(1):3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217205/