Giacomo M Bacci1, Maria A Donati2, Elisabetta Pasquini2, Francis Munier3, Catia Cavicchi4, Amelia Morrone4,5, Andrea Sodi6, Vittoria Murro6, Nuria Garcia Segarra7, Claudio Defilippi8, Leonardo Bussolin9, Roberto Caputo1. 1. Pediatric Ophthalmology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy. 2. Metabolic Disease and Newborn Screening Clinical Unit, Neuroscience Department, Meyer Children's Hospital, Florence, Italy. 3. Retinoblastoma Clinics, Oculogenetics Unit, Jules-Gonin Eye Hospital, Lausanne, Switzerland. 4. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Florence, Italy. 5. Neuroscience, Psychology, Pharmacology and Child Health Department, University of Florence, Florence, Italy. 6. Neuroscience Department, Eye Clinic, University of Florence, Florence, Italy. 7. Center for Molecular Disease, University Hospital of Vaudois, Lausanne, Switzerland. 8. Diagnostic Imaging Department, Meyer Children's Hospital, Florence, Italy. 9. Department of Pediatric Neuroanesthesia and Neuro Intensive Care Unit (ICU), Meyer Children's Hospital, Florence, Italy.
Abstract
PURPOSE: To describe the retinal structure of a group of patients affected by methylmalonic aciduria with homocystinuria cblC type, caused by mutations in the MMACHC gene, using spectral domain optical coherence tomography (SD-OCT). METHODS: Young patients (n = 11, age 0-74 months) with cblC disease, detected by newborn screening or clinically diagnosed within 40 days of life, underwent molecular analysis and complete ophthalmic examination, including fundus photography and SD-OCT. In one case, we also performed fluorescein angiography (FA) and standard electroretinography (ERG). RESULTS: Molecular analysis of the MMACHC gene fully confirmed cblC disease in nine of 11 patients. Two patients harboured only a single heterozygous pathogenic MMACHC mutation and large unbalanced rearrangements were excluded by array-CGH analysis in both. All patients except two showed a bilateral maculopathy. In general, retinal changes were first observed before one year of age and progressed to a well-established maculopathy. Measurable visual acuities ranged from normal vision, in keeping with age, to bilateral, severe impairment of central vision. Nystagmus was present in six patients. Spectral domain optical coherence tomography (SD-OCT) showed macular thinning with severe alterations in outer, and partial sparing of inner, retinal layers. CONCLUSION: Patients affected by cblC disease may frequently show an early onset maculopathy with variable ophthalmoscopic appearance. Spectral domain optical coherence tomography (SD-OCT) broadens the knowledge of subtle retinal alterations during the disease's progression and helps to shed light on the pathological mechanism of maculopathy development.
PURPOSE: To describe the retinal structure of a group of patients affected by methylmalonic aciduria with homocystinuriacblC type, caused by mutations in the MMACHC gene, using spectral domain optical coherence tomography (SD-OCT). METHODS: Young patients (n = 11, age 0-74 months) with cblC disease, detected by newborn screening or clinically diagnosed within 40 days of life, underwent molecular analysis and complete ophthalmic examination, including fundus photography and SD-OCT. In one case, we also performed fluorescein angiography (FA) and standard electroretinography (ERG). RESULTS: Molecular analysis of the MMACHC gene fully confirmed cblC disease in nine of 11 patients. Two patients harboured only a single heterozygous pathogenic MMACHC mutation and large unbalanced rearrangements were excluded by array-CGH analysis in both. All patients except two showed a bilateral maculopathy. In general, retinal changes were first observed before one year of age and progressed to a well-established maculopathy. Measurable visual acuities ranged from normal vision, in keeping with age, to bilateral, severe impairment of central vision. Nystagmus was present in six patients. Spectral domain optical coherence tomography (SD-OCT) showed macular thinning with severe alterations in outer, and partial sparing of inner, retinal layers. CONCLUSION:Patients affected by cblC disease may frequently show an early onset maculopathy with variable ophthalmoscopic appearance. Spectral domain optical coherence tomography (SD-OCT) broadens the knowledge of subtle retinal alterations during the disease's progression and helps to shed light on the pathological mechanism of maculopathy development.