Author(s)

Yasufumi Kondo^1,2, Michiaki Kinoshita^1,3*, Takuhiro Yoshida^1,4, Hisanori Matoba⁵, Takeshi Uehara⁵, Meguru Ikeyama⁶, Jun Nakayama⁶, Kunihiro Yoshida⁷, Shu-Ichi Ikeda¹

¹Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
²Department of Neurology, Komoro Kosei General Hospital, Komoro, Japan.
³Department of Neurology, Suwa Red Cross Hospital, Suwa, Japan.
⁴Department of Neurology, Ina Central Hospital, Ina, Japan.
⁵Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
⁶Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
⁷Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan.

Colony stimulating factor-1 receptor (CSF1R) plays important roles in the differentiation and proliferation of macrophage and microglia in systemic organs and the brain. A genetic defect in CSF1R causes hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS mainly affects the cerebral white matter and shows pre-senile cognitive decline, motor disturbance, and epilepsy. However, systemic manifestations outside the brain have not yet been described in patients with HDLS. Here, we report the case of a 41-year-old man with HDLS carrying the p. K793T mutation in CSF1R, who unexpectedly died of sepsis and hemophagocytic syndrome shortly after the onset of HDLS. The fetal sequence of sepsis and hemophagocytic syndrome was triggered by enterocolitis. An autopsy revealed that focal inflammation in the intestine had almost resolved. Most strikingly, massive infiltration of cluster of differentiation (CD) 68- and CD163-immunopositive macrophages with hemophagocytosis was observed in the bone marrow, spleen, and liver. Less abundant infiltration of CD68- and CD204-immunopositive macrophages without hemophagocytosis was also seen in the lung and intestine. At present, the pathogenetic link between CSF1R mutation and hemophagocytic syndrome in this patient is unclear. Our case, however, clearly shows that even in patients with HDLS, aberrant activation of functional macrophages can be induced under certain conditions in visceral organs.

HDLS (Hereditary Diffuse Leukoencephalopathy with Spheroids), CSF1R (Colony Stimulating Factor-1 Receptor), Enterocolitis, Macrophage, Hemophagocytic Syndrome

Kondo, Y. , Kinoshita, M. , Yoshida, T. , Matoba, H. , Uehara, T. , Ikeyama, M. , Nakayama, J. , Yoshida, K. and Ikeda, S. (2016) Unexpected Occurrence of Fetal Hemophagocytic Syndrome in a Patient with Hereditary Diffuse Leukoencephalopathy with Spheroids. Case Reports in Clinical Medicine, 5, 77-84. doi: 10.4236/crcm.2016.53014.