Ocular manifestations of cobalamin C type methylmalonic aciduria with homocystinuria

Fuchs, Leah R.; Robert, Matthieu P.; Ingster-Moati, I.; Couette, Lucia; Dufier, Jean‐Louis; Lonlay, Pascale de

doi:10.1016/j.jaapos.2012.02.019

Cited by 18 publications

(13 citation statements)

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“…9 Wandering eye movements, inability to fixate, and nystagmus often are the first clinical signs of eye disease in infants with cblC deficiency. 10,11 The maculopathy and progressive retinal dysfunction 11,12 are seen in most patients with early-onset cblC deficiency and rarely in those with late-onset cblC deficiency.…”

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confidence: 99%

“…12,13 The first funduscopic signs can include pigmented macular changes that progress to a bull's-eye maculopathy. This maculopathy is characterized by a hypopigmented perimacular zone surrounded by a hyperpigmented ring, typically progresses to the periphery of the retina, 9,10 and is accompanied by measurable dysfunction on electroretinography (ERG) testing. 11,14 Optic nerve atrophy also is noted frequently.…”

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Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

et al. 2016

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Ocular manifestations of cobalamin C deficiency include a developmental as well as a degenerative phenotype and lack strict correlation to metabolic status, but may be mitigated by prenatal or early treatment. Purpose To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism caused by mutations in the MMACHC gene. Design Retrospective, observational case series. Participants Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health Clinical Center between August 2004 and September 2012. Patient ages ranged from 2 to 27 years at last ophthalmic visit, and follow-up ranged from 0 to 83 months (median, 36 months; range, 13–83 months) over a total of 69 visits. Methods Best-corrected Snellen visual acuity, slit-lamp biomicroscopy, dilated fundus examination, wide-field photography, fundus autofluorescence imaging, sedated electroretinography, spectral-domain optical coherence tomography, and metabolite assessment. Main Outcome Measures Visual acuity and presence and degree of retinal degeneration and optic nerve pallor. Results Nystagmus (64%), strabismus (52%), macular degeneration (72%), optic nerve pallor (68%), and vascular changes (64%) were present. c.271dupA (p.R91KfsX14) homozygous patients (n = 14) showed early and extensive macular degeneration. Electroretinography showed that scotopic and photopic responses were reduced and delayed, but were preserved remarkably in some patients despite severe degeneration. Optical coherence tomography images through the central macular lesion of a patient with severe retinal degeneration showed extreme thinning, some preservation of retinal lamination, and nearly complete loss of the outer nuclear layer. Despite hyperhomocysteinemia, no patients exhibited lens dislocation. Conclusions This longitudinal study reports ocular outcomes in the largest group of patients with cblC deficiency systematically examined at a single center over an extended period. Differences in progression and severity of macular degeneration, optic nerve pallor, and vascular attenuation between homozygous c.271dupA (p.R91KfsX14) patients and compound heterozygotes were noted. The pace and chronicity of ophthalmic manifestations lacked strict correlation to metabolic status as measured during visits. Prenatal or early treatment, or both, may have mitigated ocular disease, leading to better functional acuity, but patients still progressed to severe macular degeneration. The effects of prenatal or early treatment, or both, in siblings, the manifestation of severe disease in infancy, the presence of comorbid developmental abnormalities (e.g., microcephaly, cardiac noncompaction), and the possible laminar structural defect noted in many patients are findings showing that cblC deficiency displays a developmental as well as a degenerative ocular phenotype.

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Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

et al. 2016

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“…The fundus appearance and fluorescein angiogram findings were similar to those described in cases of congenital MMA. 4,5 Full-field electroretinograms revealed mildly reduced scotopic and photopic responses in the left eye.…”

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“…These alterations have either been hypothesized or shown to disrupt RPE, photoreceptor, and ganglion cell function. 1,5,6 The partial reversibility of the patient's visual function may reflect the normalization of her homocysteine levels after treatment. This case suggests that vitamin B12 deficiency should be considered in the differential diagnosis of elderly patients presenting with worsening vision and macular findings that might otherwise be mistaken for new or worsening AMD.…”

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A woman with bilateral maculopathy and acquired vitamin B12 deficiency

Doan

Chao

2014

Eye

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“…[8][9][10] Handheld SDOCT can also identify retinal manifestations of systemic disease, for example, the presence of retinal edema in neonatal hemochromatosis and liver failure or retinal thinning in cobalamin C type methylmalonic aciduria with homocystinuria. 11,12 …”

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Pediatric Optical Coherence Tomography in Clinical Practice—Recent Progress

Lee

Proudlock

Gottlob

2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee H, Proudlock FA, Gottlob I. Pediatric optical coherence tomography in clinical practice-recent progress. Invest Ophthalmol Vis Sci. 2016;57:OCT69-OCT79. DOI:10.1167/iovs.15-18825 PURPOSE. Optical coherence tomography (OCT) has revolutionized the diagnosis and management of adult retinal and optic nerve disease. Children were deprived of this technology until the recent development of handheld spectral-domain OCT (HH-SDOCT). In this article, we review the applications of OCT imaging in pediatric ophthalmology.METHODS. This study was a review of the literature.RESULTS. The acquisition and interpretation of pediatric tomograms differ significantly from those for adults, with adjustments needed to account for the shorter axial lengths, higher refractive errors, and ongoing retinal and optic nerve development in the pediatric eye. Handheld SDOCT is increasingly being used as an adjunctive diagnostic tool in retinopathy of prematurity (ROP) and nonaccidental injury (NAI) by providing additional morphologic information that is not normally clinically discernible. The role of HH-SDOCT in streamlining diagnosis in infantile nystagmus syndrome, retinal dystrophies, and degenerations has been established. Optical coherence tomography can also help differentiate between pediatric intraocular tumors, for example, hamartomas and retinoblastoma; monitor tumor progression; and monitor treatment response. In addition, HH-SDOCT is establishing its role as a noninvasive monitoring tool in children affected by optic nerve pathology such as glaucoma, optic nerve atrophy and hypoplasia, optic pathway glioma, and pseudotumor cerebri. CONCLUSIONS.Handheld SDOCT can provide novel insights into the natural history of retinal and optic nerve diseases in young children. For example, in achromatopsia and albinism, in vivo OCT studies have provided evidence of altered but ongoing retinal development in early childhood, which suggests that potentially targeting treatment at an earlier age may optimize visual function by normalizing retinal development.

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Ocular manifestations of cobalamin C type methylmalonic aciduria with homocystinuria

Cited by 18 publications

References 11 publications

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

A woman with bilateral maculopathy and acquired vitamin B12 deficiency

Pediatric Optical Coherence Tomography in Clinical Practice—Recent Progress

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