Subscribe to RSS
DOI: 10.1055/a-1114-1887
Hornhautveränderungen im Säuglings- und Kindesalter als Ausdruck systemischer Stoffwechselerkrankungen
Corneal Changes in Infancy and Childhood as an Expression of Systemic Metabolic Diseases![](https://www.thieme-connect.de/media/klimo/202006/lookinside/thumbnails/10-1055-a-1114-1887_kl2148-1.jpg)
Zusammenfassung
Bilaterale Hornhauttrübungen können Ausdruck unterschiedlichster Systemerkrankungen sein. Insbesondere im Kindesalter ist hierbei differenzialdiagnostisch an diverse, aber meist sehr seltene Stoffwechselerkrankungen zu denken. Da die Hornhauttrübungen zu den ersten klinischen Symptomen dieser Erkrankungen zählen können, kommt dem Ophthalmologen eine entscheidende Rolle hinsichtlich der Einleitung einer frühen interdisziplinären diagnostischen Abklärung zu. Die frühe Diagnosestellung ist durch die daraus ggf. resultierende Therapieeinleitung für den weiteren klinischen Verlauf und die Prognose der betroffenen Patienten äußerst entscheidend.
Abstract
Bilateral corneal opacities can be a leading symptom of different systemic diseases. Especially in childhood, various metabolic diseases, although very rare, should be considered as a possible diagnosis. Since corneal opacities can be among the first clinical symptoms of these diseases, the ophthalmologist plays a central role in initiating early interdisciplinary diagnostics. The early diagnosis is extremely important for further prognosis and the clinical outcome of the affected patients due to the early initiation of therapy.
Schlüsselwörter
Kornea - Kinderophthalmologie - Mukopolysaccharidose - Mukolipidose - Zystinose - Morbus WilsonKey words
cornea - pediatric ophthalmology - mucopolysaccharidosis - mucolipidosis - cystinosis - Morbus WilsonPublication History
Received: 27 January 2020
Accepted: 14 February 2020
Article published online:
09 April 2020
Georg Thieme Verlag KG
Stuttgart · New York
-
Literatur
- 1 Bermejo E, Martinez-Frias ML. Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet 1998; 75: 497-504
- 2 Marx-Gross S, Laubert-Reh D, Schneider A. et al. The prevalence of glaucoma in young people. Dtsch Arztebl Int 2017; 114: 204-210
- 3 Nischal KK. A new approach to the classification of neonatal corneal opacities. Curr Opin Ophthalmol 2012; 23: 344-354
- 4 Rohrbach JM, Lisch W, Seitz B. Die Hornhaut als Indikator für Systemerkrankungen. Ophthalmologe 2018; 115: 975-986
- 5 Cimaz R, La Torre F. Mucopolysaccharidoses. Curr Rheumatol Rep 2014; 16: 389
- 6 Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet 1997; 101: 355-358
- 7 Ashworth JL, Biswas S, Wraith E. et al. Mucopolysaccharidoses and the eye. Surv Ophthalmol 2006; 51: 1-17
- 8 Caruso RC, Kaiser-Kupfer MI, Muenzer J. et al. Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology 1986; 93: 1612-1616
- 9 Tomatsu S, Fujii T, Fukushi M. et al. Newborn screening and diagnosis of mucopolysaccharidoses. Mol Genet Metab 2013; 110: 42-53
- 10 Berman ER. Diagnosis of metabolic eye disease by chemical analysis of serum, leukocytes and skin fibroblast tissue culture. Birth Defects Orig Artic Ser 1976; 12: 15-51
- 11 Ellinwood NM, Vite CH, Haskins ME. Gene therapy for lysosomal storage diseases: the lessons and promise of animal models. J Gene Med 2004; 6: 481-506
- 12 Kakkis ED, Muenzer J, Tiller GE. et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001; 344: 182-188
- 13 Smith JA, Chan CC, Goldin E. et al. Noninvasive diagnosis and ophthalmic features of mucolipidosis type IV. Ophthalmology 2002; 109: 588-594
- 14 Bach G. Mucolipidosis type IV. Mol Genet Metab 2001; 73: 197-203
- 15 Bargal R, Goebel HH, Latta E. et al. Mucolipidosis IV: novel mutation and diverse ultrastructural spectrum in the skin. Neuropediatrics 2002; 33: 199-202
- 16 Amir N, Zlotogora J, Bach G. Mucolipidosis type IV: clinical spectrum and natural history. Pediatrics 1987; 79: 953-959
- 17 Schiffmann R, Dwyer NK, Lubensky IA. et al. Constitutive achlorhydria in mucolipidosis type IV. Proc Natl Acad Sci U S A 1998; 95: 1207-1212
- 18 Altarescu G, Sun M, Moore DF. et al. The neurogenetics of mucolipidosis type IV. Neurology 2002; 59: 306-313
- 19 Wakabayashi K, Gustafson AM, Sidransky E. et al. Mucolipidosis type IV: an update. Mol Genet Metab 2011; 104: 206-213
- 20 Dobrovolny R, Liskova P, Ledvinova J. et al. Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation. Am J Ophthalmol 2007; 143: 663-671
- 21 Casteels I, Taylor DS, Lake BD. et al. Mucolipidosis type IV. Presentation of a mild variant. Ophthalmic Paediatr Genet 1992; 13: 205-210
- 22 Folkerth RD, Alroy J, Lomakina I. et al. Mucolipidosis IV: morphology and histochemistry of an autopsy case. J Neuropathol Exp Neurol 1995; 54: 154-164
- 23 Dong XP, Cheng X, Mills E. et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 2008; 455: 992-996
- 24 Geer JS, Skinner SA, Goldin E. et al. Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder. Pediatr Neurol 2010; 42: 223-226
- 25 Newman NJ, Starck T, Kenyon KR. et al. Corneal surface irregularities and episodic pain in a patient with mucolipidosis IV. Arch Ophthalmol 1990; 108: 251-254
- 26 Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol 2013; 28: 51-59
- 27 Manz F, Gretz N. Cystinosis in the Federal Republic of Germany. Coordination and analysis of the data. J Inherit Metab Dis 1985; 8: 2-4
- 28 Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002; 347: 111-121
- 29 Besouw M, Levtchenko E. Growth retardation in children with cystinosis. Minerva Pediatr 2010; 62: 307-314
- 30 Schnaper HW, Cottel J, Merrill S. et al. Early occurrence of end-stage renal disease in a patient with infantile nephropathic cystinosis. J Pediatr 1992; 120: 575-578
- 31 Wilmer MJ, Schoeber JP, van den Heuvel LP. et al. Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol 2011; 26: 205-215
- 32 Elmonem MA, Veys KR, Soliman NA. et al. Cystinosis: a review. Orphanet J Rare Dis 2016; 11: 47
- 33 Tsilou E, Zhou M, Gahl WA. et al. Ophthalmologic manifestations and histopathology of infantile nephropathic cystinosis: report of a case and review of the literature. Surv Ophthalmol 2007; 52: 97-105
- 34 Tsilou ET, Rubin BI, Reed GF. et al. Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis. Cornea 2002; 21: 173-176
- 35 Tsilou ET, Rubin BI, Reed G. et al. Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy. Ophthalmology 2006; 113: 1002-1009
- 36 Gahl WA, Kuehl EM, Iwata F. et al. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab 2000; 71: 100-120
- 37 Servais A, Moriniere V, Grunfeld JP. et al. Late-onset nephropathic cystinosis: clinical presentation, outcome, and genotyping. Clin J Am Soc Nephrol 2008; 3: 27-35
- 38 Anikster Y, Lucero C, Guo J. et al. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res 2000; 47: 17-23
- 39 Emma F, Nesterova G, Langman C. et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 2014; 29 (Suppl. 04) iv87-iv94
- 40 Gräf M, Grote A, Wagner F. Cysteamin-Augentropfen zur Behandlung kornealer Zystineinlagerungen bei infantiler Zystinose. Klin Monatsbl Augenheilkd 1992; 201: 48-50
- 41 Flockerzi E, Daas L, Schlötzer-Schrehardt U. et al. Ocular changes in nephropathic cystinosis: the course of the gold-dust. Int Ophthalmol 2019; 39: 1413-1418
- 42 Natt E, Westphal EM, Toth-Fejel SE. et al. Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1—q22.3 in a patient with tyrosinemia type II. Hum Genet 1987; 77: 352-358
- 43 Natt E, Kida K, Odievre M. et al. Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc Natl Acad Sci U S A 1992; 89: 9297-9301
- 44 Huhn R, Stoermer H, Klingele B. et al. Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. Hum Genet 1998; 102: 305-313
- 45 Kato M, Suzuki N, Koeda T. [A case of tyrosinemia type II with convulsion and EEG abnormality]. No To Hattatsu 1993; 25: 558-562
- 46 Chitayat D, Balbul A, Hani V. et al. Hereditary tyrosinaemia type II in a consanguineous Ashkenazi Jewish family: intrafamilial variation in phenotype; absence of parental phenotype effects on the fetus. J Inherit Metab Dis 1992; 15: 198-203
- 47 Bohnert A, Anton-Lamprecht I. Richner-Hanhartʼs syndrome: ultrastructural abnormalities of epidermal keratinization indicating a causal relationship to high intracellular tyrosine levels. J Invest Dermatol 1982; 79: 68-74
- 48 Macsai MS, Schwartz TL, Hinkle D. et al. Tyrosinemia type II: nine cases of ocular signs and symptoms. Am J Ophthalmol 2001; 132: 522-527
- 49 Bardelli AM, Borgogni P, Farnetani MA. et al. Familial tyrosinaemia with eye and skin lesions. Presentation of two cases. Ophthalmologica 1977; 175: 5-9
- 50 Paige DG, Clayton P, Bowron A. et al. Richner-Hanhart syndrome (oculocutaneous tyrosinaemia, tyrosinaemia type II). J R Soc Med 1992; 85: 759-760
- 51 Rabinowitz LG, Williams LR, Anderson CE. et al. Painful keratoderma and photophobia: hallmarks of tyrosinemia type II. J Pediatr 1995; 126: 266-269
- 52 Meikle PJ, Hopwood JJ, Clague AE. et al. Prevalence of lysosomal storage disorders. JAMA 1999; 281: 249-254
- 53 Spada M, Pagliardini S, Yasuda M. et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006; 79: 31-40
- 54 MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001; 38: 769-775
- 55 MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001; 38: 750-760
- 56 Ramaswami U, Whybra C, Parini R. et al. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr 2006; 95: 86-92
- 57 Pintos-Morell G, Beck M. Fabry disease in children and the effects of enzyme replacement treatment. Eur J Pediatr 2009; 168: 1355-1363
- 58 Nguyen TT, Gin T, Nicholls K. et al. Ophthalmological manifestations of Fabry disease: a survey of patients at the Royal Melbourne Fabry Disease Treatment Centre. Clin Exp Ophthalmol 2005; 33: 164-168
- 59 Sodi A, Ioannidis AS, Mehta A. et al. Ocular manifestations of Fabryʼs disease: data from the Fabry Outcome Survey. Br J Ophthalmol 2007; 91: 210-214
- 60 Samiy N. Ocular features of Fabry disease: diagnosis of a treatable life-threatening disorder. Surv Ophthalmol 2008; 53: 416-423
- 61 Sher NA, Letson RD, Desnick RJ. The ocular manifestations in Fabryʼs disease. Arch Ophthalmol 1979; 97: 671-676
- 62 Rohrbach JM, Szurman P, Schlote T. et al. [The lens in systemic diseases]. Klin Monatsbl Augenheilkd 2012; 229: 843-856
- 63 Orssaud C, Dufier J, Germain D. Ocular manifestations in Fabry disease: a survey of 32 hemizygous male patients. Ophthalmic Genet 2003; 24: 129-139
- 64 Pitz S, Grube-Einwald K, Renieri G. et al. Subclinical optic neuropathy in Fabry disease. Ophthalmic Genet 2009; 30: 165-171
- 65 Gitlin JD. Wilson disease. Gastroenterology 2003; 125: 1868-1877
- 66 Reilly M, Daly L, Hutchinson M. An epidemiological study of Wilsonʼs disease in the Republic of Ireland. J Neurol Neurosurg Psychiatry 1993; 56: 298-300
- 67 Tao TY, Gitlin JD. Hepatic copper metabolism: insights from genetic disease. Hepatology 2003; 37: 1241-1247
- 68 Lutsenko S, Petris MJ. Function and regulation of the mammalian copper-transporting ATPases: insights from biochemical and cell biological approaches. J Membr Biol 2003; 191: 1-12
- 69 Lossner J, Bachmann H, Siegemund R. et al. [Wilsonʼs disease in East Germany: in retrospect and perspectives – an evaluation]. Psychiatr Neurol Med Psychol (Leipz) 1990; 42: 585-600
- 70 Roberts EA, Cox DW. Wilson disease. Baillieres Clin Gastroenterol 1998; 12: 237-256
- 71 Wilson DC, Phillips MJ, Cox DW. et al. Severe hepatic Wilsonʼs disease in preschool-aged children. J Pediatr 2000; 137: 719-722
- 72 Czlonkowska A, Rodo M, Gromadzka G. Late onset Wilsonʼs disease: therapeutic implications. Mov Disord 2008; 23: 896-898
- 73 Bonelli RM, Cummings JL. Frontal-subcortical dementias. Neurologist 2008; 14: 100-107
- 74 Lang C, Müller D, Claus D. et al. Neuropsychological findings in treated Wilsonʼs disease. Acta Neurol Scand 1990; 81: 75-81
- 75 European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilsonʼs disease. J Hepatol 2012; 56: 671-685
- 76 Steindl P, Ferenci P, Dienes HP. et al. Wilsonʼs disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997; 113: 212-218
- 77 Gow PJ, Smallwood RA, Angus PW. et al. Diagnosis of Wilsonʼs disease: an experience over three decades. Gut 2000; 46: 415-419
- 78 Ala A, Walker AP, Ashkan K. et al. Wilsonʼs disease. Lancet 2007; 369: 397-408
- 79 Cairns JE, Williams HP, Walshe JM. “Sunflower cataract” in Wilsonʼs disease. Br Med J 1969; 3: 95-96
- 80 Dhawan A, Taylor RM, Cheeseman P. et al. Wilsonʼs disease in children: 37-year experience and revised Kingʼs score for liver transplantation. Liver Transpl 2005; 11: 441-448
- 81 Saeedi R, Li M, Frohlich J. A review on lecithin : cholesterol acyltransferase deficiency. Clin Biochem 2015; 48: 472-475
- 82 Kunnen S, Van Eck M. Lecithin : cholesterol acyltransferase: old friend or foe in atherosclerosis?. J Lipid Res 2012; 53: 1783-1799
- 83 Kastelein JJ, Pritchard PH, Erkelens DW. et al. Familial high-density-lipoprotein deficiency causing corneal opacities (fish eye disease) in a family of Dutch descent. J Intern Med 1992; 231: 413-419
- 84 Palmiero PA, Sbeity Z, Liebmann J. et al. In vivo imaging of the cornea in a patient with lecithin-cholesterol acyltransferase deficiency. Cornea 2009; 28: 1061-1064
- 85 Viestenz A, Schlötzer-Schrehardt U, Hofmann-Rummelt C. et al. Histopathology of corneal changes in lecithin-cholesterol acyltransferase deficiency. Cornea 2002; 21: 834-837
- 86 Rousset X, Vaisman B, Auerbach B. et al. Effect of recombinant human lecithin cholesterol acyltransferase infusion on lipoprotein metabolism in mice. J Pharmacol Exp Ther 2010; 335: 140-148
- 87 Burnett JR, Hooper AJ, McCormick SPA, Hegele RA. Tangier Disease. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A. eds. GeneReviews® . Seattle (WA): University of Washington; 2019: 1993-2020 Im Internet (Stand: 10.01.2020): https://www.ncbi.nlm.nih.gov/books/NBK549920/
- 88 Mercan M, Yayla V, Altinay S. et al. Peripheral neuropathy in Tangier disease: a literature review and assessment. J Peripher Nerv Syst 2018; 23: 88-98
- 89 Herrmann WA, Winkler von Mohrenfels C, Lohmann CP. Confocal microscopy and corneal sensitivity in a patient with corneal manifestations of Tangier disease. Cornea 2004; 23: 825-827