Abstract
Background: Cystinosis is a rare systemic lysosomal disease affecting mainly the kidney and eye. Ocular involvement in cystinosis is universal being the presence of cystine crystals in the cornea a diagnostic criterion and one of the earliest manifestations of the disease. Neuro-ophthalmologic manifestations are considered a rare and late complication in these patients. The aim of this article is to report the unexpectedly high incidence of intracranial hypertension in children with cystinosis at our centre.
Methods: This study included eight children (0–16 years of age) with cystinosis seen at the paediatric ophthalmology department, Hospital Universitari Vall d’Hebron (Barcelona, Spain), a tertiary hospital, over the last 5 years.
Results: Three girls and five boys, mean age: 9.6 years (range: 5–14 years), were studied. During follow-up, 4 out of 8 developed papilledema and confirmed high cerebrospinal fluid (CSF) pressure. The only symptomatic child presented an Arnold–Chiari anomaly with enlarged ventricles, whereas the other three, all asymptomatic, were diagnosed by scheduled fundoscopy and had normal neuroimaging studies. All four patients had at least one known risk factor for developing intracranial hypertension: initiation of growth hormone therapy, tapering of corticosteroids, acute renal failure and Arnold–Chiari malformation. Two of them required a ventriculoperitoneal shunt.
Conclusions: Our results show that intracranial hypertension can occur more frequently than expected in patients with cystinosis. Furthermore, visual prognosis depends on early diagnosis and prompt treatment. A multidisciplinary approach is necessary, and we recommend fundoscopic examinations in all paediatric patients with cystinosis whether or not they present symptoms.
My co-authors have all contributed to this manuscript: planning, conducting and reporting of the work described in the article, and approval of this submission.
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Abbreviations
- CKD:
-
Chronic kidney disease
- CSF:
-
Cerebrospinal fluid
- GFR:
-
Glomerular filtration rate
- ICP:
-
Increased intracranial pressure
- IH:
-
Intracranial hypertension
- LP:
-
Lumbar puncture
- MRI:
-
Magnetic resonance imaging
- MRV:
-
Magnetic resonance venography
- PTCS:
-
Pseudotumor cerebri syndrome
- rhGH:
-
Recombinant human growth hormone
- VA:
-
Visual acuity
References
Besouw MT, Van Dyck M, Francois I et al (2012) Detailed studies of growth hormone secretion in cystinosis patients. Pediatr Nephrol 27:2123–2127
Blethen SL, Allen DB, Graves D et al (1996) Safety of recombinant deoxyribonucleic acid-derived growth hormone: the national cooperative growth study experience. J Clin Endocrinol Metal 81:1704–1710
Darendeliler F (2009) Safety of growth hormone treatment. J Clin Res Pediatr Endocrinol 1:36–43
Dogulu CF, Tsilou E, Rubin B et al (2004) Idiopathic intracranial hypertension in cystinosis. J Pediatr 145:673–678
Dureau P, Broyer M, Dufier J (2003) Evolution of ocular manifestations in nephropathic cystinosis: a long-term study of a population treated with cysteamine. J Pediatr Ophthalmol Strabismus 40:142–146
Friedman DI, Liu GT, Digre KB (2013) Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 81:1159–1165
Gahl WA, Nesterova G (2010) Cystinosis: the post-transplant era. Eur Nephrol 4:55–61
Koller EA, Stadel BV, Malozowski SN (1997) Papilledema in 15 renally compromised patients treated with growth hormone. Pediatr Nephrol 11:451–454
Malozowski S, Tanner SA, Wysowski DK et al (1995) Benign intracranial hypertension in children with growth hormone deficiency treated with growth hormone. J Pediatr 126:996–999
Nesterova G, Gahl W (2008) Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol 23:863–878
Nesterova G, Williams C, Bernardini I et al (2015) Cystinosis: renal glomerular and renal tubular function in relation to compliance with cysteine-depleting therapy. Pediatr Nephrol 30:945–951
Parnes A, Wassner SJ, Weinstein JM (2008) A case of intracranial hypertension and papilledema associated with nephropathic cystinosis and ocular involvement. Binocul Vis Strabismus Q 23:37–40
PROCYSBI® (cysteamine bitartrate) delayed-release capsules. Label information. Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/002465/WC500151313.pdf. Accessed 22 Jan 2016
Rangwala LM, Liu GT (2007) Pediatric idiopathic intracranial hypertension. Surv Ophthalmol 52:597–617
Rao KI, Hesselink J, Trauner DA (2015) Chiari I malformation in nephropathic cystinosis. J Pediatr 167:1126–1129
Reeves GD, Doyle DA (2002) Growth hormone treatment and pseudotumor cerebri: coincidence or close relationship? J Pediatr Endocrinol Metab 15:723–730
Richler M, Milot J, Quigley M et al (1991) Ocular manifestations of nephropathic cystinosis: the French-Canadian experience in a genetically homogeneous population. Arch Ophthalmol 109:359–362
Rogers AH, Rogers GL, Bremer DL et al (1999) Pseudotumor cerebri in children receiving recombinant human growth hormone. Ophthalmology 106:1186–1190
Rogers DL, McGregor ML (2010) Increased intracranial pressure in patients with cystinosis. J Pediatr Ophthalmol Strabismus 47:e1–e3
Ross DL, Strife CF, Towbin R et al (1982) Nonabsorptive hydrocephalus associated with nephropathic cystinosis. Neurology 32:1330–1334
Souza FM, Collet-Solberg PF (2011) Adverse effects of growth hormone replacement therapy in children. Arq Bras Endocrinol Metab 55:559–565
Touchman JW, Anikster Y, Diatrich NL et al (2000) The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-Kb segment and discovery of a novel gene within the common cystinosis-causing deletion. Genome Res 10:165–173
Tsilou E, Zhou M, Gahl W et al (2007) Ophthalmic manifestations and histopathology of infantile nephropathic cystinosis: report of a case and review of the literature. Surv Ophthalmol 52:97–105
Viltz L, Trauner DA (2013) Effect of age at treatment on cognitive performance in patients with cystinosis. J Pediatr 163:489–492
Wühl E, Haffner D, Offner G et al (2001) European Study Group on Growth hormone treatment in children with nephropathic cystinosis: Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr 138:880–887
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Communicated by: Carla E. Hollak, M.D.
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Take-Home Message
Intracranial hypertension is an unexpected complication in patients with cystinosis and regular fundoscopic examinations are recommended to rule out papilledema.
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Nieves Martín-Begué, Silvia Alarcón, Charlotte Wolley-Dod, Luis Enrique Lara, Álvaro Madrid, Paola Cano, Mireia del Toro and Gema Ariceta declare that we have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in this study. Additional informed consent was obtained from all patients (or from their parents) for which identifying information is included in this article.
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Martín-Begué, N. et al. (2016). Intracranial Hypertension in Cystinosis Is a Challenge: Experience in a Children’s Hospital. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 35. JIMD Reports, vol 35. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_18
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DOI: https://doi.org/10.1007/8904_2016_18
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