It’s difficult for rare disease patients to find information about their condition and even more so for patients with medical conditions that affect very small numbers of people, like the ultra rare disease atypical HUS. Given the many variations of the disease name, accessing research can be challenging for even the most motivated aHUS patient or caregiver.
Atypical HUS is a complex disease that can affect multiple organs and symptoms. As noted in 2014 TMA research by Hofer et al 1, “extra-renal manifestations are observed in 20% of patients including involvement of the central nerve system, cardiovascular system, lungs, skin, skeletal muscle, and gastrointestinal tract.” Vision issues are mentioned in Hofer’s research in the section on Cerebrovascular TMA Manifestations, and stated here is that “central nerve system involvement is the most frequent extra-renal organ manifestation of aHUS (10-48%).” 1 The Global aHUS Patient Registry reported that extra renal manifestations (problems elsewhere than the kidneys) occur more often in adults than children, and that 6 months prior to enrollment in the Global aHUS Patient Registry, “renal manifestations were reported in 34%, gastrointestinal in 18%, cardiovascular in 15%, central nervous system in 11%, and pulmonary in 9%.” 2 A collaborative partnership with the Global aHUS Patient Registry was published in Orphanet in November 2016, with its impact detailed in a follow up article.
Atypical HUS patients and caregivers of pediatric aHUS patients mentioned vision issues as an area of concern for them in the 2016 aHUS Global Poll (see questions 39 and 40). This aHUS Alliance poll involved 233 participants from 23 nations answering 45 questions on a survey tool made available in 6 languages. Of the adult aHUS patients and caregivers of pediatric patients, 50 of 233 respondents noted that vision issues were a serious or frequent enough concern for them to mention vision issues to their doctor (Q 39). Similarly, 63 of 233 respondents reported that a doctor had told them that aHUS activity may have caused neurological such as headaches, vision issues, stroke, or seizures (Q40). Atypical HUS is more than a kidney disease, and the systemic impact of aHUS throughout the body has been outlined in aHUS Alliance overview on this topic.
In addition to anecdotal patient or caregiver reports of blurred vision or eye pain, there are some published case reports about ocular involvement (eye issues) in atypical HUS patients. One 2007 case study of a pediatric aHUS patient noted, “Ophthalmologic examination found vitreous bleeding, elevated ocular pressure, choroidal hemorrhage (ultrasound biomicroscopy) and retinal ischemia (fluorescein angiography).” 3 In that case, the child was treated with plasma exchanges which lead to a decrease in ocular pain and improvement in visual acuity and other ophthalmologic measures. A more recent case report of an adult female presenting with involvement of multiple body systems and organs described, “a case of aHUS with bilateral central retinal artery and vein occlusion, vitreous hemorrhage, and blindness that improved following eculizumab therapy”. 4 It is important to note that currently many nations have limited or no drug access to complement inhibitor eculizumab as an aHUS treatment option (see aHUS Alliance white paper, Access to aHUS Treatment).
In a 2013 edition of Eye, the Scientific Journal of the Royal College of Opthamologists, a case study was published regarding a female aHUS patient who presented in the last trimester of pregnancy with a form of retinal detachment (SRD) in addition to preeclampsia and HELLP syndrome (see aHUS & Pregnancy). Genetic variants and various types of ocular involvement were mentioned in that case study. “Research linked aHUS to genetic abnormalities in the complement system proteins like: factor H, factor I, membrane co-factor protein, factor CD46, factor B, and C3. Ocular manifestations are rare and include retinal, choroidal, and vitreal hemorrhages, retinal ischemic signs, and non-perfusion.” 5 Translational science across medical specialties and genetic research is highlighting the possibilities for previously unknown links among medical conditions. “Age-related macular degeneration (AMD) and cuticular drusen (CD), a clinical subtype of AMD, have been linked to genetic variants in the complement factor H (CFH) gene.” 6 Better understanding of the roles that genetics may play in complement associated diseases and their range of symptoms will help fill in current knowledge gaps.
The role of complement seems to be popping up across a broad area of research topics, to include atypical HUS. “Abnormalities in FH are associated with the renal diseases atypical hemolytic uremic syndrome and dense deposit disease and the ocular disease age-related macular degeneration. Although FH systemically controls complement activation, clinical phenotypes selectively manifest in kidneys and eyes, suggesting the presence of tissue-specific determinants of disease development.” 7 There seems interest as well as need to further examine the interface of patient genetic profiles regarding the expression and impact of aHUS activity.
Atypical HUS patients, and the medical teams who treat them, do need to be aware that aHUS issues can occur in throughout the body to affect multiple systems and organs. Much remains to be learned about the interplay of TMA activity, vision issues, genetics, and complement dysregulation. Atypical HUS patients experiencing vison issues need to alert their doctor and medical care specialists, as eye problems might be a sign of TMA activity and could signal potential for other neurological involvement. What steps might aHUS patients and caregivers of pediatric caregivers take regarding their vision? Getting regular professional eye care is part of maintaining healthy vision. As with most health issues, early detection and early intervention can improve patient outcomes. After discussing with your doctor any new or unusual eye symptoms, consider seeing an ophthalmologist, an eye MD or DO who specializes in eye and vision care. For vision issues or any aspects of rare disease care, this might be the mantra of patients, caregivers, and medical staff alike – be observant, continue to learn, ask questions, make connections.
L Burke, March 2017
(Updated Jan 2018)
Hofer et al. Extra-Renal Manifestations of Complement-Mediated Thrombotic Microangiopathies. Front Pediatr. 2014; 2: 97. 2014 Sep 8. doi: 10.3389/fped.2014.00097
Scully, M. et al. Systemic Involvement at Entry into the Global Atypical Hemolytic Uremic Syndrome (aHUS) Registry. ASH 2016, San Diego Annual Meeting. 5 Dec 2016, 3729: Session 311.
Larakeb A et al. Ocular involvement in hemolytic uremic syndrome due to factor H deficiency–are there therapeutic consequences? Pediatr Nephrol. 2007 Nov;22(11):1967-70. Epub 2007 Jul 10.
Greenwood, Gregory. Case report of atypical hemolytic uremic syndrome with retinal arterial and venous occlusion treated with eculizumab. Int Med Case Rep J 2015; 8: 235–239. 2015 Oct 13. doi: 10.2147/IMCRJ.S90640.
David R et al. Resolution of ocular involvement with systemic eculizumab therapy in atypical hemolytic-uremic syndrome. Eye (Lond). 2013 Aug; 27(8): 997–998. doi: 10.1038/eye.2013.111
Duvvari, M et al. Analysis of rare variants in the CFH gene in patients with the cuticular drusen subtype of age-related macular degeneration. Mol Vision. Mar 2015; 21: 285–292. PMCID: PMC4360166
Loeven M et al. Mutations in Complement Factor H Impair Alternative Pathway Regulation on Mouse Glomerular Endothelial Cells in Vitro. J Biol Chem. 2016 Mar 4;291(10):4974-81. doi: 10.1074/jbc.M115.702506.
More Info – aHUS & Vision
Sturm, V et al. Ocular involvement in paediatric haemolytic uraemic syndrome. Acta Ophthalmologica, 88: 804–807. doi:10.1111/j.1755-3768.2009.01552.x
Ustaoğlu M et al, 2017 Purtscher-Like Retinopathy Associated with Atypical Hemolytic Uremic Syndrome Turk J Ophthalmol. 2017 Dec; 47(6): 348–350.
Zheng X et al. Recurrent ocular involvement in pediatric atypical hemolytic uremic syndrome. J Pediatr Ophthalmol Strabismus. 2014 Oct 1;51 Online:e 62-5. doi: 10.3928/01913913-20140923-03.
2016 aHUS Global Poll – FMI and to see Poll Results 2016 aHUS Global Poll