Moya-moya disease in a child with nephropatic cystinosis: a case report and literature review

The article presents a case report of a child with a combination of two ultra rare diseases: nephropathic cystinosis and moya-moya disease.

Cystinosis is an autosomal recessive lysosomal storage disorder characterized by accumulation of cystine in lysosomes throughout the body. Cystinosis is caused by mutations in the CTNS gene that encodes the lysosomal cystine carrier protein cystinosin. The lack of functional cystinosin causes accumulation and crystallization of cystine within the lysosomes, which leads to apoptosis and tissue damage in all organs. The disease is characterized by renal (Fanconi syndrome with progressive decline in renal function) and extrarenal manifestations in the form of hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, coronary vascular calcification, metabolic bone disease, damage to the central nervous system with cortical atrophy, cerebral calcification and etc.

Moya-moya disease is a progressive condition that can lead to ischemic stroke or intracranial hemorrhage in children and adults. The following types of this condition are distinguished: moya-moya disease primary (idiopathic) refers to patients with angiographic evidence of the disease, who may have a genetic predisposition, but do not have concomitant diseases and moya-moya syndrome – angiographic changes in patients are the same as in patients with moya-moya disease, but there is an underlying disease that is the cause.

We analyzed the probable changes in the central nervous system during cystinosis and concluded that the underlying disease cannot be the cause of the identified changes and when observing this patient, we encountered two independent conditions, which required a team approach to determining treatment tactics and further observation.

Timely diagnosis made it possible to improve the further prognosis of the disease, but also the patient’s quality of life, stop episodes of cerebral ischemia, and prevent the development of neurological deficits.

1. Belousova E.D., Vlodavets D.V. Episodic ataxia. Trudnyy patsient = Difficult Patient 2006;37–41. (In Russ.).

2. Esin R.G., Isaeva Yu.N., Gorobets E.A. et al. Moyamoya disease. Zhurnal nevrologii i psikhiatrii = Journal of Neurology and Psychiatry 2016;(4):74–8. (In Russ.). DOI: 17116/jnevro20161164174-78

3. Shchederkina I.O., Orlova K.A., Koltunov I.E. et al. Difficulties in differential diagnosis of epileptic and hypocalcemic seizures in children and adolescents. Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics 2018;10(1S):66–74. (In Russ.). DOI: 10.14412/2074-2711-2018-1S-66-74

4. Arias E.J., Derdeyn C.P., Dacey R.G.Jr., Zipfel G.J. Advances and surgical considerations in the treatment of moyamoya disease. Neurosurgery 2014;74:S116. DOI: 10.1227/NEU.0000000000000229

5. Вeghi E., Carpio A., Forsgren L. et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010;51:671–5. DOI: 10.1111/j.1528-1167.2009.02285

6. Brosius S.N., Vossough A., Fisher M.J. et al. Characteristics of moyamoya syndrome in pediatric patients with neurofibromatosis type 1. Pediatr Neurol 2022;134:85. DOI: 10.1016/j.pediatrneurol.2022.05.013

7. Carlson C.B., Harvey F.H., Loop J. Progressive alternating hemiplegia in early childhood and basal arterial stenosis and telangiectasia (moyamoya syndrome). Neurology 1973;23:734. DOI: 10/1212/wnl.23.7.734

8. Castilla-Guerra L., del Carmen Fernandez-Moreno M., Lopez-Chozas J.M., Fernandez-Bolanos R. Electrolytes disturbances and seizures. Epilepsia 2006;47(12):1990–8. DOI: 10.1111/j.1528-1167.2006.00861

9. Cerrato P., Grasso M., Lentini A. et al. Atherosclerotic adult moyamoya disease in a patient with hyperhomocysteinaemia. Neurol Sci 2007;28:45. DOI: 10.1007/10072-007-0748-6

10. Cherqui S., Courtoy P.J. The renal Fanconi syndrome in cystinosis: Pathogenic insights and therapeutic perspectives. Nat Rev Nephrol 2017;13:115–31. DOI: 10.1038/nrneph.2016.182

11. Chie N., Takeshi M., Ryo U. et al. Moyamoya disease with epileptic nystagmus: A case report. J Clin Neurosci 2019;70:251–4. DOI: 10.1016/j.jocn.2019.08.069

12. Choi J.U., Kim D.S., Kim E.Y., Lee K.C. Natural history of moyamoya disease: Comparison of activity of daily living in surgery and non surgery groups. Clin Neurol Neurosurg 1997;99(Suppl 2): S11–8. DOI: 10.1016/s0303-8467(97)00033-4

13. Czartoski T., Hallam D., Lacy J.M. et al. Postinfectious vasculopathy with evolution to moyamoya syndrome. J Neurol Neurosurg Psychiatry 2005;76:256–9. DOI: 10.1136/jnnp.2004.041046

14. Duan L., Wei L., Tian Y. et al. Novel susceptibility loci for moyamoya disease revealed by a genome-wide association study. Stroke 2018;49:11–8. DOI: 10.1161/strokeaha.117.017430

15. Emma F., Nesterova G., Langman C. et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 2014;29(4):87–94. DOI: 10.1093/ndt/gfu090

16. Filippopulos F.M., Schnabel L., Dunker K. et al.Episodic ataxias in children and adolescents: Clinical findings and suggested diagnostic criteria. Front Neurol Sec Pediatric Neurology 2022;13:24. DOI: 10.3389/fneur.2022.1016856

17. Frechette E.S., Bell-Stephens T.E., Steinberg G.K., Fisher R.S. Electroencephalographic features of moyamoya in adults. Clin Neurophysiol 2015;126:481. DOI: 10.1016/j.cliph.2014.06.033

18. Fung L.W., Thompson D., Ganesan V. Revascularisation surgery for paediatric moyamoya: A review of the literature. Childs Nerv Syst 2005;21(5):358. DOI: 10.1007/s00381-004-1118-9

19. Gahl W.A., Thoene J.G., Schneider J.A. Cystinosis. N Engl J Med 2002;347:111–21. DOI: 10.1056/NEJMra020552

20. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis). Neurol Med Chir (Tokyo) 2012;52(5):245–66. DOI: 10/2176/nmc.52245

21. Gupta M., Choudhri O.A., Feroze A.H. et al. Management of moyamoya syndrome in patients with Noonan syndrome. J Clin Neurosci 2016;28:107–11. DOI: 10.1016/j.jocn.2015.11.017

22. Ihara M., Yamamoto Y., Hattori Y. et al. Moyamoya disease: Diagnosis and interventions. Lancet Neurol 2022;21:747–58. DOI: 10/1016/S1474-4422(22)00165-X

23. Ikeda H., Sasaki T., Yoshimoto T. et al. Mapping of a familial moyamoya disease gene to chromosome 3p24.2–p26. Am J Hum Genet 1999;64:533–7. DOI: 10.1086/302243

24. Imaizumi M., Nukada T., Yoneda S. et al. Tuberous sclerosis with moyamoya disease. Case report. Med J Osaka Univ 1978;28:345–53.

25. Inoue T.K., Ikezaki K., Sasazuki T. et al. Linkage analysis of moyamoya disease on chromosome 6. J Child Neurol 2000;15:179–82. DOI: 10.1177/088307380001500307

26. Irene T., Francesco B. First attack and clinical presentation of hemiplegic migraine in pediatric age: A multicenter retrospective study and literature review. Front Neurol 2019;10:1079. DOI: 10.3389/fneur.2019.01079

27. Jea A., Smith E.R., Robertson R., Scott R.M. Moyamoya syndrome associated with Down syndrome: Outcome after surgical revascularization. Pediatrics 2005;116:694. DOI: 10.1542/peds.2005-0568

28. Jia Lu., Qing X., Tuanfeng Y. et al. Electroencephalographic features in pediatric patients with moyamoya disease in China. Rong Wang Chinese Neurosurg J 2020;6:3 DOI: 10.1186/s41016-019-0179-2

29. Kamada F., Aoki Y., Narisawa A. et al. A genome-wide association study identifies RNF213 as the first moyamoya disease gene. J Hum Genet 2011;56(1):34–40. DOI: 10.1038/jhg.2010.132

30. Kang H.S., Kim J.H., Phi J.H. et al. Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease. J Neurol Neurosurg Psychiatry 2010;81:673. DOI: 10.1136/jnnp.2009.191817

31. Kaoru Sakurai K., Horiuchi Y., Ikeda H. et al. A novel susceptibility locus for moyamoya disease on chromosome 8q23. J Hum Genet 2004;49:278. DOI: 10/1007/s10038-004-0143-6

32. Kawai M., Nishikawa T., Tanaka M. et al. An autopsied case of Williams syndrome complicated by moyamoya disease. Acta Paediatr Jpn 1993;35:63. DOI: 10.1111/j1442-200x.1993.tb03009

33. Kim S.K., Seol H.J., Cho B.K. et al. Moyamoya disease among young patients: Its aggressive clinical course and the role of active surgical treatment. Neurosurgery 2004;54(4):840. DOI: 10.1227/01.neu.0000114140.41509.12

34. Kitano S., Sakamoto H., Fujitani K., Kobayashi Y. Moyamoya disease associated with a brain stem glioma. Childs Nerv Syst 2000;16:251–5. DOI: 10.1007/s003810050508

35. Lee S.J., Ahn J.Y. Stenosis of the proximal external carotid artery in an adult with moyamoya disease: Moyamoya or atherosclerotic change? Neurol Med Chir (Tokyo) 2007;47:356–9. DOI: 10.2176/nmc.47.356

36. Lee S., Rivkin M.J., Kirton A. et al. Moyamoya disease in children: Results from the international pediatric stroke study. J Child Neurol 2017;32:924–9. DOI: 10.1177/0883073817718730

37. Meyer S., Zanardo L., Kaminski W.E. et al. Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with severe moyamoya disease. Br J Dermatol 2005;153:431. DOI: 10.1111/j.1365-2133.2005.06658

38. Mineharu Y., Takenaka K., Yamakawa H. et al. Inheritance pattern of familial moyamoya disease: Autosomal dominant mode and genomic imprinting. J Neurol Neurosurg Psychiatry 2006;77:1025. DOI: 10/1136/jnnp.2006.096040

39. Nijasri Charnnarong S., José B., Nordli D. et al. Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis. Available at: https://pro.uptodatefree.ir/Show/1131.

40. Nzwalo H., Santos V., Gradil C. et al. Caucasian familial moyamoya syndrome with rare multisystemic malformations. Pediatr Neurol 2013;48:240–3. DOI: 10.1016/j.pediatrneurol.2012.11.009

41. Park M., Helip-Wooley A., Thoene J. Lysosomal cysteine storage augments apoptosis in cultured human fibroblasts and renal tubular epithelial cells. J Am Soc Nephrol 2002;13:2878–87. DOI: 10.1097/01.asn.0000036867.49866.59

42. Rocha R., Soro I., Leitão A. et al. Moyamoya vascular pattern in Alagille syndrome. Pediatr Neurol 2012;47:125. DOI: 10.1016/jpediatrneurol.2012.04.014

43. Scott R.M., Smith E.R. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009;360:1226. DOI: 10.1056/NEJMra0804622

44. Servais A., Saitovitch A., Hummel A. et al. Central nervous system complications in adult cystinosis patients. J Inherit Metab Dis 2020;43(2):348–56. DOI: 10.1002/jimd.12164

45. Smith E.R., Scott R.M. Spontaneous occlusion of the circle of Willis in children: Pediatric moyamoya summary with proposed evidence-based practice guidelines. A review. J Neurosurg Pediatr 2012;9:353. DOI: 10.3171/2011.12.PEDS1172

46. Spengos K., Tsivgoulis G., Toulas P. et al. Hyperventilationenhanced chorea as a transient ischemic phenomenon in a patient with moyamoya disease. Eur Neurol 2004;51:172. DOI: 10.1159/000077665

47. Sui-yi X., Hui-Juan L., Jing H. et al. Migraine with brainstem aura accompanied by disorders of consciousness. J Pain Res 2021;14:1119–27. DOI: 10.2147/JPR.S305483

48. Teo M., Johnson J.N., Bell-Stephens T.E. et al. Surgical outcomes of Majewski osteodysplastic primordial dwarfism type II with intracranial vascular anomalies. J Neurosurg Pediatr 2016; 25:717. DOI: 103171/2016.6.PEDS16243

49. Tokuç G., Minareci O., Yavuzer D. et al. Moyamoya syndrome in a child with hyperphosphatasia. Pediatr Int 1999;41:399.

50. Yamada I., Himeno Y., Matsushima Y., Shibuya H. Renal artery lesions in patients with moyamoya disease: Angiographic findings. Stroke 2000;31:733. DOI: 10/1161/01.str.31.3.733

51. Yonggang M., Meng Zh. Risk factors for epilepsy recurrence after revascularization in pediatric patients with moyamoya disease. J Stroke Cerebrovasc Dis 2018;26:740–6. DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.012