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Klin Monbl Augenheilkd 2020; 237(06): 761-771
DOI: 10.1055/a-1114-1887
Übersicht

Hornhautveränderungen im Säuglings- und Kindesalter als Ausdruck systemischer Stoffwechselerkrankungen

Corneal Changes in Infancy and Childhood as an Expression of Systemic Metabolic Diseases
Michael Reich
1   Klinik für Augenheilkunde, Universitätsklinikum Freiburg
2   Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
,
Thomas Reinhard
1   Klinik für Augenheilkunde, Universitätsklinikum Freiburg
2   Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
,
Wolf Alexander Lagrèze
1   Klinik für Augenheilkunde, Universitätsklinikum Freiburg
2   Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
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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 Wilson

Key words

cornea - pediatric ophthalmology - mucopolysaccharidosis - mucolipidosis - cystinosis - Morbus Wilson


Publikationsverlauf

Eingereicht: 27. Januar 2020

Angenommen: 14. Februar 2020

Artikel online veröffentlicht:
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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 3 Nischal KK. A new approach to the classification of neonatal corneal opacities. Curr Opin Ophthalmol 2012; 23: 344-354
    CrossrefPubMedGoogle Scholar
  • 4 Rohrbach JM, Lisch W, Seitz B. Die Hornhaut als Indikator für Systemerkrankungen. Ophthalmologe 2018; 115: 975-986
    CrossrefPubMedGoogle Scholar
  • 5 Cimaz R, La Torre F. Mucopolysaccharidoses. Curr Rheumatol Rep 2014; 16: 389
    CrossrefPubMedGoogle Scholar
  • 6 Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet 1997; 101: 355-358
    CrossrefPubMedGoogle Scholar
  • 7 Ashworth JL, Biswas S, Wraith E. et al. Mucopolysaccharidoses and the eye. Surv Ophthalmol 2006; 51: 1-17
    CrossrefPubMedGoogle Scholar
  • 8 Caruso RC, Kaiser-Kupfer MI, Muenzer J. et al. Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology 1986; 93: 1612-1616
    CrossrefPubMedGoogle Scholar
  • 9 Tomatsu S, Fujii T, Fukushi M. et al. Newborn screening and diagnosis of mucopolysaccharidoses. Mol Genet Metab 2013; 110: 42-53
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 12 Kakkis ED, Muenzer J, Tiller GE. et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001; 344: 182-188
    CrossrefPubMedGoogle Scholar
  • 13 Smith JA, Chan CC, Goldin E. et al. Noninvasive diagnosis and ophthalmic features of mucolipidosis type IV. Ophthalmology 2002; 109: 588-594
    CrossrefPubMedGoogle Scholar
  • 14 Bach G. Mucolipidosis type IV. Mol Genet Metab 2001; 73: 197-203
    CrossrefPubMedGoogle Scholar
  • 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
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Amir N, Zlotogora J, Bach G. Mucolipidosis type IV: clinical spectrum and natural history. Pediatrics 1987; 79: 953-959
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 18 Altarescu G, Sun M, Moore DF. et al. The neurogenetics of mucolipidosis type IV. Neurology 2002; 59: 306-313
    CrossrefPubMedGoogle Scholar
  • 19 Wakabayashi K, Gustafson AM, Sidransky E. et al. Mucolipidosis type IV: an update. Mol Genet Metab 2011; 104: 206-213
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 21 Casteels I, Taylor DS, Lake BD. et al. Mucolipidosis type IV. Presentation of a mild variant. Ophthalmic Paediatr Genet 1992; 13: 205-210
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 24 Geer JS, Skinner SA, Goldin E. et al. Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder. Pediatr Neurol 2010; 42: 223-226
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 26 Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol 2013; 28: 51-59
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 28 Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002; 347: 111-121
    CrossrefPubMedGoogle Scholar
  • 29 Besouw M, Levtchenko E. Growth retardation in children with cystinosis. Minerva Pediatr 2010; 62: 307-314
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 31 Wilmer MJ, Schoeber JP, van den Heuvel LP. et al. Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol 2011; 26: 205-215
    CrossrefPubMedGoogle Scholar
  • 32 Elmonem MA, Veys KR, Soliman NA. et al. Cystinosis: a review. Orphanet J Rare Dis 2016; 11: 47
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 35 Tsilou ET, Rubin BI, Reed G. et al. Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy. Ophthalmology 2006; 113: 1002-1009
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 38 Anikster Y, Lucero C, Guo J. et al. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res 2000; 47: 17-23
    CrossrefPubMedGoogle Scholar
  • 39 Emma F, Nesterova G, Langman C. et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 2014; 29 (Suppl. 04) iv87-iv94
    CrossrefPubMedGoogle Scholar
  • 40 Gräf M, Grote A, Wagner F. Cysteamin-Augentropfen zur Behandlung kornealer Zystineinlagerungen bei infantiler Zystinose. Klin Monatsbl Augenheilkd 1992; 201: 48-50
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 51 Rabinowitz LG, Williams LR, Anderson CE. et al. Painful keratoderma and photophobia: hallmarks of tyrosinemia type II. J Pediatr 1995; 126: 266-269
    CrossrefPubMedGoogle Scholar
  • 52 Meikle PJ, Hopwood JJ, Clague AE. et al. Prevalence of lysosomal storage disorders. JAMA 1999; 281: 249-254
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 57 Pintos-Morell G, Beck M. Fabry disease in children and the effects of enzyme replacement treatment. Eur J Pediatr 2009; 168: 1355-1363
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 60 Samiy N. Ocular features of Fabry disease: diagnosis of a treatable life-threatening disorder. Surv Ophthalmol 2008; 53: 416-423
    CrossrefPubMedGoogle Scholar
  • 61 Sher NA, Letson RD, Desnick RJ. The ocular manifestations in Fabryʼs disease. Arch Ophthalmol 1979; 97: 671-676
    CrossrefPubMedGoogle Scholar
  • 62 Rohrbach JM, Szurman P, Schlote T. et al. [The lens in systemic diseases]. Klin Monatsbl Augenheilkd 2012; 229: 843-856
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 64 Pitz S, Grube-Einwald K, Renieri G. et al. Subclinical optic neuropathy in Fabry disease. Ophthalmic Genet 2009; 30: 165-171
    CrossrefPubMedGoogle Scholar
  • 65 Gitlin JD. Wilson disease. Gastroenterology 2003; 125: 1868-1877
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 67 Tao TY, Gitlin JD. Hepatic copper metabolism: insights from genetic disease. Hepatology 2003; 37: 1241-1247
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 70 Roberts EA, Cox DW. Wilson disease. Baillieres Clin Gastroenterol 1998; 12: 237-256
    CrossrefPubMedGoogle Scholar
  • 71 Wilson DC, Phillips MJ, Cox DW. et al. Severe hepatic Wilsonʼs disease in preschool-aged children. J Pediatr 2000; 137: 719-722
    CrossrefPubMedGoogle Scholar
  • 72 Czlonkowska A, Rodo M, Gromadzka G. Late onset Wilsonʼs disease: therapeutic implications. Mov Disord 2008; 23: 896-898
    CrossrefPubMedGoogle Scholar
  • 73 Bonelli RM, Cummings JL. Frontal-subcortical dementias. Neurologist 2008; 14: 100-107
    CrossrefPubMedGoogle Scholar
  • 74 Lang C, Müller D, Claus D. et al. Neuropsychological findings in treated Wilsonʼs disease. Acta Neurol Scand 1990; 81: 75-81
    PubMedGoogle Scholar
  • 75 European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilsonʼs disease. J Hepatol 2012; 56: 671-685
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 77 Gow PJ, Smallwood RA, Angus PW. et al. Diagnosis of Wilsonʼs disease: an experience over three decades. Gut 2000; 46: 415-419
    CrossrefPubMedGoogle Scholar
  • 78 Ala A, Walker AP, Ashkan K. et al. Wilsonʼs disease. Lancet 2007; 369: 397-408
    CrossrefPubMedGoogle Scholar
  • 79 Cairns JE, Williams HP, Walshe JM. “Sunflower cataract” in Wilsonʼs disease. Br Med J 1969; 3: 95-96
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 81 Saeedi R, Li M, Frohlich J. A review on lecithin : cholesterol acyltransferase deficiency. Clin Biochem 2015; 48: 472-475
    CrossrefPubMedGoogle Scholar
  • 82 Kunnen S, Van Eck M. Lecithin : cholesterol acyltransferase: old friend or foe in atherosclerosis?. J Lipid Res 2012; 53: 1783-1799
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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/
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar