Abstract
Inherited metabolic diseases are rare genetic disorders caused by synthesis disorders affecting protein, carbohydrate and lipid metabolisms, impaired enzyme activity, and deficiency of cofactors or transporters. More than 1000 inherited metabolic diseases have been reported. The prevalence of each disease is rare. However, the overall prevalence is not rare as expected. Inherited metabolic diseases can occur at any age, from prenatal to adulthood. The clinical features are mostly progressive when left untreated. Most diseases occur at young ages and often with more than one organ involvement. In Inherited metabolic diseases, eye involvement may be primary or secondary, and the findings may be local or systemic. The toxic effect of abnormal metabolites or accumulation of normal metabolites is usually responsible for the pathogenesis. Early recognition of treatable inherited metabolic diseases is important as it may change the treatment outcome of the patient. Ophthalmological findings may be in the form of cataract, corneal clouding, retinitis pigmentosa, cherry red spot and optic atrophy. Bilateral symmetrical involvement is expected. In this article, eye findings that can be seen in hereditary metabolic diseases will be discussed.
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References
- Saudubray JM, Garcia-Cazorla A. Inborn errors of metabolism overview: pathophysiology, manifestations, evaluation, and management. Pediatr Clin 2018;65:179-208.
- Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 2006;91:896-9.
- Stark KL, Gibson JB, Hertle RW, Brodsky MC. Ocular motor signs in an infant with carbohydrate-deficient glycoprotein syndrome type Ia. Am J Ophthalmol 2000;130:533-5.
- Germain DP, Arad M, Burlina A, Perry ME, Bruno F, Ulla FR, et al. The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – a systematic literature review by a European panel of experts. Mol Genet Metab 2019;126:224–35.
- Winter AW, Salimi A, Ospina LH, Roos JCP. Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder. Br J Ophthalmol 2019;103:315-26.
- Veys KRP, Elmonem MA, Van Dyck M, Janssen MC, Cornelissen EAM, Hohenfellner K, et al. Chitotriosidase as a novel biomarker for therapeutic monitoring of nephropathic cystinosis. J Am Soc Nephrol 2020;31:1092–106.
- Wong VG, Lietman PS, Seegmiller JE. Alterations of pigment epithelium in cystinosis. Arch Ophthalmol 1967;77:361-9.
- Wang LR, McIntyre AD, Hegele RA. Complex genetic architecture in severe hypobetalipoproteinemia. Lipids Health Dis 2018;17:48.
- Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis.2008;3:19.
- Bronstein AM, Patel M, Arshad Q. A brief review of the clinical anatomy of the vestibular-ocular connectionsdhow much do we know? Eye 2015;29:163-70.
- Macsai MS, Schwartz TL, Hinkle D, Hummel MB, Mulhern MG, Rootman D. Tyrosinemia type II: nine case of ocular signes and symptoms. Am J Ophthalmol 2001;132:522-7.
- Teodorak BP, Scaini G, Cavalho-Silva M, Gomes LM, Teixeira LJ, Rebelo J, et al. Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L-tyrosine. Metab Brain Dis 2017;32:557–64.
- Welsink-Karssies MM, Oostrom KJ, Hermans ME, Hollak CEM, Janssen MCH, Langendonk JG, et al. Classical galactosemia: neuropsychological and psychosocial functioning beyond intellectual abilities. Orphanet J Rare Dis 2020;15:42.
- Wilson MP, Plecko B, Mills PB, Clayton PT. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis 2018;42:629– 46.
- Neeleman RA, van Beers EJ, Friesema EC, Koole-Lesuis R, van der Pol WL, Wilson JHP, et al. Clinical remission of delta-aminolevulinic acid dehydratase defciency through suppression of erythroid heme synthesis. Hepatology 2019;70: 434–6.
- Özdek Ş, Sarı A, Bilgihan K, Akata F, Hasanreisoğlu B. Surgical treatment of hereditary lens subluxations. Ophthalmic Surg and Lasers 2002;33:309-13.
- Weber Hoss GR, Sperb-Ludwig F, Schwartz IV, Blom HJ. Classical homocystinuria: a common inborn error of metabolism? An epidemiological study based on genetic databases. Mol Genet Genomic Med 2020;8:e1214.
- Ahtam B, Waisbren SE, Anastasoaie V, Berry GT, Brown M, Petrides S, et al. Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia . J Inherit Metab Dis 2020;43:1205-18.
- Hennermann JB, Schadewaldt P, Vetter B, Shin YS, Mönch E, Klein J. Features and outcome of galactokinase defciency in children diagnosed by newborn screening. J Inherit Metab Dis 2011;34:399–407.
- Ho AC, Fung CW, Siu TS, Ma OCK, Lam CW, Tam S, et al. Lathosterolosis: a disorder of cholesterol biosynthesis resembling smith-lemli-opitz syndrome. JIMD Rep 2014;12:129–34.
- Folz SJ, Trobe JD. The peroxisome and the eye. Surv Ophthalmol 1991;35:353-68.
- Ferdinandusse S, Denis S, van Roermund CWT, Preece MY, Koster J, Ebberink MS, et at. A novel case of ACOX2 defciency leads to recognition of a third human peroxisomal acyl-CoA oxidase. BBA Mol Basis Dis 2018;1864:952–8.
- Martinelli D, Fiermonte G, Häberle J, Boenzi S, Goffredo BM, Travaglini L, et al. CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Eur J Hum Genet 2020;28:982-7.
- Santinelli R, Costagliola C, Tolone C, D’Aloia A, D’Avanzo A, Prisco F, et al. Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up. J Inherit Metab Dis 2004;27:187–96.
- Kozich V, Ditrói T, SokolováJ, Křížková M, Krijt J, Ješina P, et al. Sulfurome analysis in patients with homocystinurias and ultra-rare inborn error s of hydrogen sulfide metabolism. J Inherit Metab Dis 2019;42:125-96.
- Bublil EM, Majtan T. Classical homocystinuria: from cystathionine beta-synthase defciency to novel enzyme therapies. Biochimie 2020;173:48–56.
- Xu M, Yamada T, Sun Z, Eblimit A, Lopez I, Wang F, et al. Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. Hum Mol Genet 2016;25:1479–88.
- Martinelli D, Diodato D, Ponzi E, Monné M, Boenzi S, Bertini E, et al. The hyperornithinema-hyperammonemia-homocitrullinuria syndrome. Orphanet J Rare Dis 2015;10-29.
- Mole SE, Cotman SL. Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta 2015;1852:2237–41.
- Butz ES, Chandrachud U, Mole SE, Cotman SL. Moving towards a new era of genomics in the neuronal ceroid lipofuscinoses. Biochim Biophys Acta Mol basis Dis 2020;1866-916.
- Bonello M, Ray P. A case of ataxia with isolated vitamin E deficiency Initially diagnosed as Friedreich’s ataxia. Case Reports in Neurological Medicine 2016;2016:8342653.
- Weustenfeld M, Eidelpes R, Schmuth M, Rizzo WB, Zschocke J, Keller MA. Genotype and phenotype variability in Sjögren-Larsson syndrome. Hum Mutat 2019;40:177–86.
- Egan RA, Weleber RG, Hogarth P, Gregory A, Coryell J, Westaway SK, et al. Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). Am J Ophthalmol 2005;140:267-74.
- Breiden B, Sandhoff K. Mechanism of secondary ganglioside and lipid accumulation in lysosomal disease. Int J Mol 2020;21:2566.
- Patterson MC, Mengel E, Vanier MT, Moneuse P, Rosenberg D, Pineda M. Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease type C: a fnal report of the NPC registry. Orphanet J Rare Dis 2020;15:104.
- Mueller N, Sassa T, Morales-Gonzalez S, Schneider J, Salchow DJ, Seelow D, et al. De novo mutation in ELOVL1 causes ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy. J Med Genet 2019;56:164–75.
- Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, et al. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet 2013;44:1035-9.
- Kim HL, Schuster SC. Poor Man’s 1000 genome project: recent human population expansion confounds the detection of disease alleles in 7,098 complete mitochondrial genomes. Front Genet 2013;4:13.
- Bowne SJ, Sullivan LS, Mortimer SE, Hedstrom L, Zhu J, Spellicy CJ, et al. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis. Invest Ophthalmol Vis Sci 2006;47:34-42.
- Widgren P, Hurme A, Falck A, Keski-Filppula R, Remes AM, Moilanen J, et al. Genetic aetiology of ophthalmological manifestations in children - a focus on mitochondrial disease-related symptoms. Acta Ophthalmol 2016;94:83-91.
- Lee SJ, Na JH, Han J, Lee YM. Ophthalmoplegia in mitochondrial disease. Yonsei Med J 2018;59:1190-6.
- Kwon JM, Matern D, Kurtzberg J, Wrabetz L, Gelb MH, Wenger DA, et al. Consensus guidelines for newborn screening, diagnosis and treatment of infantile Krabbe disease. Orphanet J Rare Dis 2018;13:30.
- Yee RD, Cogan DG, Zee DS. Ophthalmoplegia and dissociated nystagmus in abetalipoproteinemia. Arch Ophthalmol 1976;94:571-75.
- Gessler DJ, Li D, Xu H, Su Q, Sanmiguel J, Tuncer S, et al. Redirecting N-acetylaspartate metabolism in the central nervous system normalizes myelination and rescues Canavan disease. JCI Insight 2017;2:90807.
Abstract
Kalıtsal Metabolik Hastalıklar; protein, karbonhidrat ve lipid metabolizmalarını etkileyen sentez bozukluklarından, bozulmuş enzim aktivitesi, kofaktör veya taşıyıcı protein eksikliğinden kaynaklanan nadir görülen genetik bozukluklardır. 1000’den fazla hastalık bildirilmiştir. Metabolik hastalıklar her biri ayrı ayrı düşünüldüklerinde seyrek görüldükleri düşünülse de toplu olarak düşünüldüğünde önemli bir grup hastalığı oluşturmaktadır. Kalıtsal metabolik hastalıklar doğum öncesi dönemden yetişkinliğe kadar her yaşta ortaya çıkabilir. Klinik özellikler tedavi edilmediği taktirde çoğunlukla ilerleyicidir. Çoğu hastalık; genç yaşlarda ve sıklıkla birden fazla organ tutulumu ile ortaya çıkar. Kalıtsal metabolik hastalıklarda göz tutulumu primer veya sekonder olabileceği gibi bulgular lokal veya sistemik olabilir. Patogenezden genellikle anormal metabolitlerin toksik etkisi veya normal metabolitlerin birikimi sorumludur. Tedavi edilebilir kalıtsal metabolik hastalıkların erken tanınması, hastanın tedavi sonucunu değiştirebileceği için önemlidir. Oftalmolojik bulgular katarakt, korneal bulanıklık, retinitis pigmentoza, kiraz kırmızısı leke ve optik atrofi şeklinde olabilir. Bilateral simetrik tutulum beklenmektedir. Bu makalede kalıtsal metabolik hastalıklarda görülebilecek göz bulguları tartışılacaktır.
Project Number
-
References
- Saudubray JM, Garcia-Cazorla A. Inborn errors of metabolism overview: pathophysiology, manifestations, evaluation, and management. Pediatr Clin 2018;65:179-208.
- Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 2006;91:896-9.
- Stark KL, Gibson JB, Hertle RW, Brodsky MC. Ocular motor signs in an infant with carbohydrate-deficient glycoprotein syndrome type Ia. Am J Ophthalmol 2000;130:533-5.
- Germain DP, Arad M, Burlina A, Perry ME, Bruno F, Ulla FR, et al. The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – a systematic literature review by a European panel of experts. Mol Genet Metab 2019;126:224–35.
- Winter AW, Salimi A, Ospina LH, Roos JCP. Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder. Br J Ophthalmol 2019;103:315-26.
- Veys KRP, Elmonem MA, Van Dyck M, Janssen MC, Cornelissen EAM, Hohenfellner K, et al. Chitotriosidase as a novel biomarker for therapeutic monitoring of nephropathic cystinosis. J Am Soc Nephrol 2020;31:1092–106.
- Wong VG, Lietman PS, Seegmiller JE. Alterations of pigment epithelium in cystinosis. Arch Ophthalmol 1967;77:361-9.
- Wang LR, McIntyre AD, Hegele RA. Complex genetic architecture in severe hypobetalipoproteinemia. Lipids Health Dis 2018;17:48.
- Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis.2008;3:19.
- Bronstein AM, Patel M, Arshad Q. A brief review of the clinical anatomy of the vestibular-ocular connectionsdhow much do we know? Eye 2015;29:163-70.
- Macsai MS, Schwartz TL, Hinkle D, Hummel MB, Mulhern MG, Rootman D. Tyrosinemia type II: nine case of ocular signes and symptoms. Am J Ophthalmol 2001;132:522-7.
- Teodorak BP, Scaini G, Cavalho-Silva M, Gomes LM, Teixeira LJ, Rebelo J, et al. Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L-tyrosine. Metab Brain Dis 2017;32:557–64.
- Welsink-Karssies MM, Oostrom KJ, Hermans ME, Hollak CEM, Janssen MCH, Langendonk JG, et al. Classical galactosemia: neuropsychological and psychosocial functioning beyond intellectual abilities. Orphanet J Rare Dis 2020;15:42.
- Wilson MP, Plecko B, Mills PB, Clayton PT. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis 2018;42:629– 46.
- Neeleman RA, van Beers EJ, Friesema EC, Koole-Lesuis R, van der Pol WL, Wilson JHP, et al. Clinical remission of delta-aminolevulinic acid dehydratase defciency through suppression of erythroid heme synthesis. Hepatology 2019;70: 434–6.
- Özdek Ş, Sarı A, Bilgihan K, Akata F, Hasanreisoğlu B. Surgical treatment of hereditary lens subluxations. Ophthalmic Surg and Lasers 2002;33:309-13.
- Weber Hoss GR, Sperb-Ludwig F, Schwartz IV, Blom HJ. Classical homocystinuria: a common inborn error of metabolism? An epidemiological study based on genetic databases. Mol Genet Genomic Med 2020;8:e1214.
- Ahtam B, Waisbren SE, Anastasoaie V, Berry GT, Brown M, Petrides S, et al. Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia . J Inherit Metab Dis 2020;43:1205-18.
- Hennermann JB, Schadewaldt P, Vetter B, Shin YS, Mönch E, Klein J. Features and outcome of galactokinase defciency in children diagnosed by newborn screening. J Inherit Metab Dis 2011;34:399–407.
- Ho AC, Fung CW, Siu TS, Ma OCK, Lam CW, Tam S, et al. Lathosterolosis: a disorder of cholesterol biosynthesis resembling smith-lemli-opitz syndrome. JIMD Rep 2014;12:129–34.
- Folz SJ, Trobe JD. The peroxisome and the eye. Surv Ophthalmol 1991;35:353-68.
- Ferdinandusse S, Denis S, van Roermund CWT, Preece MY, Koster J, Ebberink MS, et at. A novel case of ACOX2 defciency leads to recognition of a third human peroxisomal acyl-CoA oxidase. BBA Mol Basis Dis 2018;1864:952–8.
- Martinelli D, Fiermonte G, Häberle J, Boenzi S, Goffredo BM, Travaglini L, et al. CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Eur J Hum Genet 2020;28:982-7.
- Santinelli R, Costagliola C, Tolone C, D’Aloia A, D’Avanzo A, Prisco F, et al. Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up. J Inherit Metab Dis 2004;27:187–96.
- Kozich V, Ditrói T, SokolováJ, Křížková M, Krijt J, Ješina P, et al. Sulfurome analysis in patients with homocystinurias and ultra-rare inborn error s of hydrogen sulfide metabolism. J Inherit Metab Dis 2019;42:125-96.
- Bublil EM, Majtan T. Classical homocystinuria: from cystathionine beta-synthase defciency to novel enzyme therapies. Biochimie 2020;173:48–56.
- Xu M, Yamada T, Sun Z, Eblimit A, Lopez I, Wang F, et al. Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. Hum Mol Genet 2016;25:1479–88.
- Martinelli D, Diodato D, Ponzi E, Monné M, Boenzi S, Bertini E, et al. The hyperornithinema-hyperammonemia-homocitrullinuria syndrome. Orphanet J Rare Dis 2015;10-29.
- Mole SE, Cotman SL. Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta 2015;1852:2237–41.
- Butz ES, Chandrachud U, Mole SE, Cotman SL. Moving towards a new era of genomics in the neuronal ceroid lipofuscinoses. Biochim Biophys Acta Mol basis Dis 2020;1866-916.
- Bonello M, Ray P. A case of ataxia with isolated vitamin E deficiency Initially diagnosed as Friedreich’s ataxia. Case Reports in Neurological Medicine 2016;2016:8342653.
- Weustenfeld M, Eidelpes R, Schmuth M, Rizzo WB, Zschocke J, Keller MA. Genotype and phenotype variability in Sjögren-Larsson syndrome. Hum Mutat 2019;40:177–86.
- Egan RA, Weleber RG, Hogarth P, Gregory A, Coryell J, Westaway SK, et al. Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). Am J Ophthalmol 2005;140:267-74.
- Breiden B, Sandhoff K. Mechanism of secondary ganglioside and lipid accumulation in lysosomal disease. Int J Mol 2020;21:2566.
- Patterson MC, Mengel E, Vanier MT, Moneuse P, Rosenberg D, Pineda M. Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease type C: a fnal report of the NPC registry. Orphanet J Rare Dis 2020;15:104.
- Mueller N, Sassa T, Morales-Gonzalez S, Schneider J, Salchow DJ, Seelow D, et al. De novo mutation in ELOVL1 causes ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy. J Med Genet 2019;56:164–75.
- Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, et al. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet 2013;44:1035-9.
- Kim HL, Schuster SC. Poor Man’s 1000 genome project: recent human population expansion confounds the detection of disease alleles in 7,098 complete mitochondrial genomes. Front Genet 2013;4:13.
- Bowne SJ, Sullivan LS, Mortimer SE, Hedstrom L, Zhu J, Spellicy CJ, et al. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis. Invest Ophthalmol Vis Sci 2006;47:34-42.
- Widgren P, Hurme A, Falck A, Keski-Filppula R, Remes AM, Moilanen J, et al. Genetic aetiology of ophthalmological manifestations in children - a focus on mitochondrial disease-related symptoms. Acta Ophthalmol 2016;94:83-91.
- Lee SJ, Na JH, Han J, Lee YM. Ophthalmoplegia in mitochondrial disease. Yonsei Med J 2018;59:1190-6.
- Kwon JM, Matern D, Kurtzberg J, Wrabetz L, Gelb MH, Wenger DA, et al. Consensus guidelines for newborn screening, diagnosis and treatment of infantile Krabbe disease. Orphanet J Rare Dis 2018;13:30.
- Yee RD, Cogan DG, Zee DS. Ophthalmoplegia and dissociated nystagmus in abetalipoproteinemia. Arch Ophthalmol 1976;94:571-75.
- Gessler DJ, Li D, Xu H, Su Q, Sanmiguel J, Tuncer S, et al. Redirecting N-acetylaspartate metabolism in the central nervous system normalizes myelination and rescues Canavan disease. JCI Insight 2017;2:90807.
Details
| Primary Language | English |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | REVIEW |
| Authors | |
| Project Number | - |
| Early Pub Date | May 18, 2023 |
| Publication Date | November 27, 2023 |
| Submission Date | March 27, 2023 |
| Published in Issue | Year 2023 Volume: 17 Issue: 6 |
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