Familial Hemophagocytic Lymphohistiocytosis in a Pediatric Patient Diagnosed by Brain Magnetic Resonance Imaging

M. E. van Egmond; R. J. Vermeulen; C.M.P.C. D. Peeters-Scholte; P. Augoustides-Savvopoulou; F. Abbink; J. J. Boelens; M. S. van der Knaap

doi:10.1055/s-0031-1287788

Neuropediatrics, Table of Contents

Neuropediatrics 2011; 42(05): 191-193
DOI: 10.1055/s-0031-1287788

Short Communication

Familial Hemophagocytic Lymphohistiocytosis in a Pediatric Patient Diagnosed by Brain Magnetic Resonance Imaging

M. E. van Egmond

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

²Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands

,

R. J. Vermeulen

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

,

C.M.P.C. D. Peeters-Scholte

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

³Department of Child Neurology, Leiden University Medical Center, Leiden, The Netherlands

,

P. Augoustides-Savvopoulou

⁴1st Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece

,

F. Abbink

⁵Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands

,

J. J. Boelens

⁶Department of Pediatric Immunology/Hematology and Blood and Marrow Transplantation, University Medical Center Utrecht, Utrecht, The Netherlands

⁷Shared corresponding authorship

,

M. S. van der Knaap

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

⁷Shared corresponding authorship

› Author Affiliations

Abstract

Familial hemophagocytic lymphohistiocytosis (fHLH) is an autosomal recessive disorder characterized by proliferation and infiltration of several organs by activated lymphocytes and macrophages. Without allogeneic stem cell transplantation, fHLH is fatal. We describe a previously healthy 11-month-old boy with a rapidly progressive encephalopathy. An older brother died at 8 months following a subacute encephalopathy diagnosed as meningoencephalitis. The family history led to the suspicion of a metabolic disease, but metabolic studies were unrevealing. MRI showed multiple inhomogeneous signal abnormalities in the cortex and white matter, most prominent in the cerebral hemispheres and around the dentate nucleus. Gadolinium-enhanced T₁-weighted images showed a multitude of enhancing foci, suggestive of perivascular enhancement. Based on MRI pattern with multiple lesions, perivascular enhancement and family history, fHLH was suspected. DNA analysis showed that the patient was compound-heterozygous for the c.445 G>A (p.Gly149Ser) mutation in exon 1 and the c.757 G>A (p.Glu253Lys) mutation in exon 2 of the perforin 1 gene. The patient was treated according to the international HLH-2004 protocol (dexamethasone, etoposide, cyclosporine, intrathecal methotrexate and prednisolone) followed by allogeneic cord blood transplantation. He showed a significant neurological and radiological improvement. The reported case demonstrates that MRI pattern recognition can lead to early diagnosis of fHLH, with subsequent adequate treatment.

Key words

familial hemophagocytic lymphohistiocytosis - magnetic resonance imaging - perivascular enhancement - allogeneic stem cell transplantation

Full Text

References

References
1 Aricò M, Janka G, Fischer A et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996; 10: 197-203
2 Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009; 127-131
3 Gurgey A, Aytac S, Balta G et al. Central nervous system involvement in Turkish children with primary hemophagocytic lymphohistiocytosis. J Child Neurol 2008; 23: 1293-1294
4 Haddad E, Sulis ML, Jabado N et al. Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis. Blood 1997; 89: 794-800
5 Henter JI, Nennesmo I. Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis. J Pediatr 1997; 130: 358-365
6 Henter JI, Horne A, Aricó M et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124-131
7 Janka GE, Schneider EM. Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol 2004; 124: 4-14
8 Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007; 166: 95-109
9 Puliyel MM, Rose W, Kumar S et al. Prolonged neurologic course of familial hemophagocytic lymphohistiocytosis. Pediatr Neurol 2009; 41: 207-210
10 zur Stadt U, Rohr J, Seifert W et al. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet 2009; 85: 482-492