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Juvenile Onset Splenomegaly and Oculopathy Due to Germline Mutation in ALPK1

  • Linqing Zhong
  • Jun Wang
  • Wei Wang
  • Lin Wang
  • Meiying Quan
  • Xiaoyan Tang
  • Lijuan Gou
  • Min Wei
  • Juan Xiao
  • Tiannan Zhang
  • Ruifang Sui
  • Qing Zhou
  • Hongmei SongEmail author
Original Article

Abstract

ROSAH syndrome was recently identified as an autosomal dominant systemic disorder due to mutations in ALPK1. It was characterized by retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. We collected and summarized the clinical data of two patients with juvenile onset splenomegaly and oculopathy. Whole exome sequencing (WES) was adapted for genetic analysis. Mutations in ALPK1 were confirmed by Sanger sequencing. Besides juvenile oculopathy and splenomegaly, both patients had intermittent fever and anhidrosis. Patient 2 also experienced recurrent upper respiratory infections in her infancy and developed dental and nail problems in childhood. Elevated TNF-α was their prominent laboratory features. Both patients were found to have a previously reported mutation, c.710C>T, p. T237M (NM_001102406) in ALPK1. Anti-TNF treatment of adalimumab was applied to patient 1, after which her optic disc edema in the left eye continued and the visual acuity deteriorated further. Patient 1 underwent elective splenectomy due to concern for spontaneous rupture of the spleen. Up to date, 18 patients of ROSAH syndrome have been reported. The clinical manifestations were relatively homogeneous, prominently presenting with juvenile onset oculopathy and splenomegaly. As it mainly involves ocular fundus, severe oculopathy deeply affects the quality of life and prognosis of ROSAH patients. Now little has been known about its treatment. As a newly recognized inherited systemic disorder, ROSAH syndrome needs to be paid more attention to, especially for those with juvenile onset splenomegaly and oculopathy.

Keywords

ALPK1 NF-κB pathway splenomegaly oculopathy autoinflammatory diseases 

Notes

Funding

This work was supported by the Public Welfare Scientific Research Project of China [grant number 201402012], CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses to HW [grant number 2016ZX310182-1], CAMS Initiative for Innovative Medicine [grant number 2016-I2M-1-008], and the Capital Health Research and Development of Special [grant number 2016-2-40114].

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Linqing Zhong
    • 1
  • Jun Wang
    • 2
  • Wei Wang
    • 1
  • Lin Wang
    • 1
  • Meiying Quan
    • 1
  • Xiaoyan Tang
    • 1
  • Lijuan Gou
    • 1
  • Min Wei
    • 1
  • Juan Xiao
    • 1
  • Tiannan Zhang
    • 1
  • Ruifang Sui
    • 3
  • Qing Zhou
    • 2
  • Hongmei Song
    • 1
    Email author
  1. 1.Department of PediatricsPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.Life Sciences InstituteZhejiang UniversityHangzhouChina
  3. 3.Department of OphthalmologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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