Investigative Ophthalmology & Visual Science Cover Image for Volume 61, Issue 7
June 2020
Volume 61, Issue 7
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ARVO Annual Meeting Abstract  |   June 2020
ROSAH syndrome, a multisystem retinal disorder due to ALPK1 mutation: ophthalmic progression, systemic and inflammatory features
Robyn V Jamieson; Amin Sabri; Anson Cheng; Nina Mustafic; Steven Eamegdool; John R Grigg
Author Affiliations & Notes
  • Robyn V Jamieson
    Eye Genetics Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia
    Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, New South Wales, Australia
  • Amin Sabri
    Eye Genetics Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia
    Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, New South Wales, Australia
  • Anson Cheng
    Eye Genetics Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia
    Save Sight Institute, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  • Nina Mustafic
    Save Sight Institute, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  • Steven Eamegdool
    Eye Genetics Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia
  • John R Grigg
    Eye Genetics Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia
    Save Sight Institute, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Robyn Jamieson, None; Amin Sabri, None; Anson Cheng, None; Nina Mustafic, None; Steven Eamegdool, None; John Grigg, None
  • Footnotes
    Support  NHMRC APP1099165
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4473. doi:
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      Robyn V Jamieson, Amin Sabri, Anson Cheng, Nina Mustafic, Steven Eamegdool, John R Grigg; ROSAH syndrome, a multisystem retinal disorder due to ALPK1 mutation: ophthalmic progression, systemic and inflammatory features. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4473.

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Abstract

Purpose : ROSAH syndrome (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis and Headaches) is caused by a recurrent de novo heterozygous variant in ALPK1, c.710C>T, [p.Thr237Met]). For characterisation of ophthalmic disease progression and other phenotypic properties, we examined retinal biomarkers, and systemic and inflammatory features in six affected individuals.

Methods : In ROSAH syndrome patients, spectral domain optical coherence tomography (SD-OCT), central macular thickness (CMT), retinal nerve fibre layer thickness (RNFL) and ellipsoid zone (EZ) length were assessed. Ultra-widefield fundus autofluorescence (UW-FAF) identified patterns of change by qualitative grading (Hypo-AF/Hyper-AF areas). Cerebral MRI scans were undertaken and T1 and T2 weighted images assessed.

Results : Three children (6 eyes), ages 7, 9 and 12 years were followed over 4 years. In these eyes, mean BCVA at presentation was 0.76 ± 0.29 logMar and at last follow-up was 0.91 ± 0.32 logMar. Mean CMT at presentation was 605 ± 134 microns and at last visit was 426 ± 171 microns, following topical carbonic anhydrase inhibitor (brinzolamide) therapy. Mean RNFL at presentation was 279 ± 145 microns and at last visit was 272 ± 28 microns. At all visits the ellipsoid zone was blurred and discontinuous. All eyes showed marked cystoid macular edema. Four eyes showed subretinal fluid and this persisted in two eyes for the follow-up period. Four eyes had a band of diffuse hyperAF around the posterior pole just outside the vascular arcades. Three affected individuals at ages 35, 38 and 65 years, had end-stage retinal disease. Cerebral MRI revealed T2 hyperintensity in the right subthalamic nucleus in one case, and patches of T2 hyperintensity in the white matter in two cases. Clinical features in all individuals indicated immunity dysfunction with marked susceptibility to infections, and abnormal inflammatory responses.

Conclusions : In ROSAH syndrome, due to mutation in ALPK1, multimodal imaging highlights progressive loss of photoreceptor function in a large area encompassing the posterior pole during the childhood years, with concomitant persistent thickening of the RNFL. The ophthalmic disease findings and progression, and other systemic features including changes on cerebral MRI, are indicative of photoreceptor and inflammatory dysfunction.

This is a 2020 ARVO Annual Meeting abstract.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2025 Association for Research in Vision and Ophthalmology.
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