Genotypic spectrum of ABCA4-associated retinal degenerations in 211 unrelated Mexican patients: identification of 22 novel disease-causing variants.

The purpose of this study was to analyze and molecularly describe the largest group of patients with ABCA4-associated retinal degeneration in Latin America. Pathogenic variants in ABCA4, a member of the ATP Binding Cassette (ABC) transporters superfamily, is one of the most common causes of inherited visual deficiency in humans. Retinal phenotypes associated with genetic defects in ABCA4 are collectively known as ABCA4-associated retinal degenerations (ABCA4R), a group of recessively inherited disorders associated with a high allelic heterogeneity. While large groups of Caucasian and Asiatic individuals suffering from ABCA4R have been well characterized, molecular information from certain ethnic groups is limited or unavailable, precluding a more realistic knowledge of ABCA4-related mutational profile worldwide. In this study, we describe the molecular findings of a large group of 211 ABCA4R index cases from Mexico. Genotyping was performed using either next generation sequencing (NGS) of a retinal dystrophy genes panel or exome. ABCA4 targeted mutation testing was applied to a subgroup of subjects in whom founder mutations were suspected. A total of 128 different ABCA4 pathogenic variants were identified, including 22 previously unpublished variants. The most common type of genetic variation was single nucleotide substitutions which occurred in 92.7% (408/440 alleles). According to the predicted protein effect, the most frequent variant type was missense, occurring in 83.5% of disease-causing alleles (368/440). Mutations such as p.Ala1773Val are fully demonstrated as a founder effect in native inhabitants of certain regions of Mexico. This study also gives us certain indications of other founder effects that need to be further studied in the near future. This is the largest molecularly characterized ABCA4R Latin American cohort, and our results supports the value of conducting genetic screening in underrepresented populations for a better knowledge of the mutational profile leading to monogenic diseases.

Macular dystrophies associated with Stargardt-like phenotypes / Distrofias maculares associadas a fenótipos Stargardt-like

ABSTRACT Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

RESUMO Objetivo: Fenótipos Stargardt-like já foram asso-ciados a variantes patogênicas no gene ABCA4. O propósito desse estudo é descrever quatro pacientes com achados retinianos semelhantes a doença de Stargardt com resultados moleculares diferentes do esperado. Métodos: Esse relato fez a revisão de prontuários médicos de quatro pacientes com distrofia macular e achados clínicos sugestivos de doença de Stargardt. Foram realizados avaliação oftalmológica, exames de imagens e testes usando next generation sequencing para avaliar variantes patogênicas associadas aos fenótipos dos pacientes. Resultados: Os pacientes apresentavam atrofia macular e alterações pigmentares sugerindo achados clínicos de doença de Stargardt. Dois pacientes foram associados a genes com herança autossômica dominante (RIMS1 e CRX) e dois pacientes foram associados a genes com herança autossômica recessiva (CRB1 e RDH12) com variantes preditoras de serem patogênicas. Conclusão: Distrofias maculares podem ter similaridades fenotípicas com fenótipo de Stargardt-like associados a outros genes além dos classicamente já descritos.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family / Mutação c.582-1G>A do gene PRPH2 causando distrofia macular de início adulto com fenótipo de distrofia macular anular concêntrica benigna em uma família

ABSTRACT The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

RESUMO Mutações do gene da periferina (PRPH2) estão associadas à disfunção das células fotorreceptoras e estão envolvidas em várias distrofias retinianas hereditárias. A mutação c.582-1G>A do gene PRPH2 é uma variante rara, relatada na retinite pigmentosa e nas distrofias em padrão. O caso 1 foi de uma mulher de 54 anos com atrofia bilateral do epitélio pigmentar da retina perifoveal e da coriocapilar, com acometimento foveolar central. A autofluorescência e a angiofluoresceinografia revelaram atrofia perifoveal do epitélio pigmentar da retina, com efeito de janela anular, sem o sinal da "coroide escura". O caso 2 (mãe) apresentava extensa atrofia do epitélio pigmentar da retina e da coriocapilar. Foi feito um estudo do gene PRPH2, que identificou a mutação c.582-1G>A em heterozigose. Foi proposto um diagnóstico de distrofia macular anular concêntrica benigna de início adulto em estágio avançado. A mutação c.582-1G>A é pouco conhecida e não está presente em todos os bancos de dados genômicos usuais. Este é o primeiro relato de caso publicado de uma mutação c.582-1G>A associada à distrofia macular anular concêntrica benigna.

Stargardt Disease Due to an Intronic Mutation in the ABCA4: A Case Report.

Purpose: To report on a patient with Stargardt disease (STGD1) and with an intronic mutation in the ABCA4 gene. Patients and Methods: A 69-year-old female patient presented to the clinic complaining of progressive vision loss. The ophthalmic evaluation was remarkable for a best corrected visual acuity of counting fingers at 5' in the right eye and 3' in the left eye. Imaging revealed deep extensive atrophy of the central macula, epithelial pigment hyperplasia, and other areas of multifocal atrophy in the right eye. Furthermore, fundus autofluorescence imaging of the macula showed central hypoautofluorescence with bilateral expansion to the periphery in both eyes. A full-field electroretinogram showed a normal rod response, with decreased cone response, bilaterally. Genetic testing was positive for a homozygous intronic mutation in the ABCA4 gene of the variant c.5714+5G>A. Conclusions and Importance: Patients with STGD1 due to presumed mild or moderate mutations in the ABCA4 gene may have a more severe presentation and progression of the disease. Based on this, the first report of a genotype-phenotype correlation in a Puerto Rican patient with STGD1 disease, genotyping all Puerto Rican patients is warranted.

Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1.

Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carrying ABCA4 and USH2A pathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl born from non-consanguineous parents. Both parents were asymptomatic and denied family history of ocular disease. Clinical history and ophthalmologic examination of the proband were consistent with Stargardt disease. Whispered voice testing disclosed moderate hearing loss. Next-generation sequencing and Sanger sequencing identified pathogenic variants in ABCA4 (c.4926C>G and c.5044_5058del) and USH2A (c.2276G>T). All variants were present homozygously in DNA from the proband and heterozygously in DNA from the father. No variants were found in maternal DNA. Further analysis of single nucleotide polymorphisms confirmed paternal UPD of chromosome 1. This is the first known patient with confirmed UPD for two recessively mutated IRD genes. Our study expands on the genetic heterogeneity of IRDs and highlights the importance of UPD as a mechanism of autosomal recessive disease in non-consanguineous parents. Moreover, a long-term follow-up is essential for the identification of retinal features that may develop as a result of USH2A-related conditions.

Evaluating vision-specific quality of life and functional vision in a Brazilian population with Stargardt disease.

PURPOSE: To compare the vision-specific quality of life (QoL) of individuals with Stargardt disease (STGD) with that of healthy individuals and to investigate the association between vision-specific QoL and functional vision. METHODS: This cross-sectional study included 41 patients with STGD and 46 healthy volunteers matched by age and gender. Best corrected visual acuity (BCVA) was used to calculate the Functional Acuity Score (FAS) and Goldmann perimetry the Functional Field Score (FFS). These scores were combined to obtain the Functional Vision Score (FVS). Vision-specific QoL was assessed using the 25-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). RESULTS: The groups had similar sociodemographic and clinical characteristics. There were significant differences in BCVA, vision-specific QoL assessed by the NEI VFQ-25, and FVS (p < 0.001) between individuals with STGD and controls. The final total score and all the subscales of the NEI VQF-25 questionnaire were significantly lower in the STGD group (p < 0.001), except for the subscales general health, color vision, and ocular pain. NEI VFQ-25 results in the STGD group were positively correlated with family income, FVS, and FFS. FVS was the score best correlated with the NEI VFQ-25 total score. CONCLUSIONS: Individuals with STGD had significant impairment of vision-specific QoL and functional vision compared with controls and the FVS was the objective evaluation method most correlated with vision-specific QoL in this population.

Unusual clinical phenotype of Stargardt disease / Fenótipo clínico incomum da doença de Stargardt

ABSTRACT Mutations in the ABCA4 gene are a common cause of Stargardt disease; however, other retinal phenotypes have also been associated with mutations in this gene. We describe an observational case report of an unusual clinical phenotype of Stargardt disease. The ophthalmological examination included best corrected visual acuity, color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. Targeted next-generation sequencing of 99 genes associated with inherited retinal dystrophies was performed in the index patient. A 48-year-old woman presented with a best corrected visual acuity of 20/25 and 20/20. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence findings were consistent with pattern dystrophy. Pattern electroretinogram demonstrated bilateral decrease of p50 values. Genetic testing identified two heterozygous missense mutations, c.428C>T, p.(Pro143Leu) and c.3113C>T, p.(Ala.1038Val), in the ABCA4 gene. Based on our results, we believe that these particular mutations in the ABCA4 gene could be associated with a specific disease phenotype characterized by funduscopic appearance similar to pattern dystrophy. A detailed characterization of the retinal phenotype in patients carrying specific mutations in ABCA4 is crucial to understand disease expression and ensure optimal clinical care for patients with inherited retinal dystrophies.

RESUMO Mutações no gene ABCA4 são causa comum da doença de Stargardt, mas outros fenótipos da retina também foram associados a mutações nesse gene. Apresentamos um relato de caso observacional de um fenótipo clínico incomum da doença de Stargardt. O exame oftalmológico incluiu a acuidade visual com melhor correção, fotografia em cores e com autofluorescência, angiofluoresceinografia, tomografia de coerência óptica e testes de eletrofisiologia. Na paciente em questão, realizou-se o sequenciamento de próxima geração de 99 genes associados a distrofias retinais hereditárias. Tratava-se de uma mulher de 48 anos com melhor acuidade visual corrigida de 20/25 e 20/20. A fundoscopia revelou lesões puntiformes amarelas perifoveais. Os resultados da angiofluoresceinografia e da autofluorescência do fundo de olho foram consistentes com distrofia em padrão. A eletrorretinografia por padrões mostrou diminuição bilateral dos valores de p50. Os testes genéticos revelaram duas mutações missense heterozigóticas, c.428C>T, p. (Pro143Leu) e c.3113C>T, p. (Ala.1038Val), no gene ABCA4. Nossos resultados nos fazem pensar que essas mutações específicas em ABCA4 talvez possam estar associadas a um fenótipo específico da doença, caracterizado por uma aparência fundoscópica semelhante à da distrofia em padrão. Uma caracterização detalhada do fenótipo da retina em pacientes portadores de mutações específicas em ABCA4 é crucial para compreender a expressão da doença e para garantir o tratamento clínico ideal para pacientes com distrofias retinais hereditárias.

Clinical and Genetic Spectrum of Stargardt Disease in Argentinean Patients.

PURPOSE: To describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients. METHODS: This retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients. RESULTS: We found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes. CONCLUSION: This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.

Depression and quality of life in individuals with Stargardts disease / Depressão e qualidade de vida em indivíduos com doença de Stargardt

ABSTRACT Objectives To assess depression and quality of life in individuals with Stargardt's disease (SD), macular dystrophy whose central vision loss begins in the first decades of life. Methods This observational, cross-sectional study included 41 SD patients and 46 healthy controls, aged 18 to 63 years old, in Minas Gerais, Brazil. Major depression episode was assessed by the Mini International Neuropsychiatric Interview, depressive symptomatology by the Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAM-D) and quality of life by the National Eye Institute Visual Function Questionnaire. The comparison between sociodemographic variables, quality of life and depression was performed using Fisher's exact test and Mann-Whitney-Wilcoxon test. Results The prevalence of depression was 12.2% in the sample with SD while in the control group was 8.7% (p = 0.614). No significant differences were observed between patients and the control group regarding the prevalence of depression and sociodemographic variables. Patients with SD had overall lower quality of life scores (59.7 vs. 88.7, p < 0.001), and presented inverse correlation between depressive symptoms, as assessed by BDI (Rho = -0.49, p < 0.001) and by HAM-D (Rho = -0.45, p = 0.003) with quality of life scores. Conclusion Depressive symptoms were the major factors affecting quality of life, regardless of sociodemographic data. Individuals with SD may develop copying strategies, seek mental care to prevent the increase of depression and decrease of quality of life.

RESUMO Objetivos Avaliar a depressão e a qualidade de vida em indivíduos com doença de Stargardt (DS), distrofia macular cuja perda de visão central se inicia nas primeiras décadas de vida. Métodos Este estudo observacional e transversal incluiu 41 pacientes com DS e 46 controles saudáveis, com idades entre 18 e 63 anos, em Minas Gerais, Brasil. Episódio de depressão maior foi avaliado pelo Mini Internacional Neuropsychiatric Interview (MINI)-PLUS, a sintomatologia depressiva, pelo Inventário de Depressão de Beck (BDI) e pela Escala de Depressão de Hamilton (HAM-D) e a qualidade de vida, pelo Questionário de Função Visual do Instituto de Olhos Nacional versão de 25 itens (NEI VFQ-25). A comparação entre as variáveis sociodemográficas, a qualidade de vida e a depressão foi realizada por meio do teste exato de Fisher e o teste de Mann-Whitney-Wilcoxon. Resultados A prevalência de depressão foi de 12,2% na amostra com indivíduos com DS, enquanto no grupo controle foi de 8,7% (p = 0,614). Não foram observadas diferenças significativas entre os pacientes e o grupo controle quanto à prevalência de depressão e às variáveis sociodemográficas. Os pacientes com DS apresentaram menor pontuação geral de qualidade de vida (59,7 vs. 88,7, p < 0,001), cujas variáveis com correlação inversa e estatisticamente significante (p < 0,05) foram as de sintomatologia depressiva, avaliadas pelo BDI ( Rho = -0,49, p < 0,001) e pelo HAM-D ( Rho = -0,45, p = 0,003). Conclusão Os sintomas depressivos foram os principais fatores que afetaram a qualidade de vida, independentemente dos dados sociodemográficos. Indivíduos com DS podem desenvolver estratégias de enfrentamento e procurar assistência mental para evitar o aumento da depressão e a diminuição da qualidade de vida.

Fundus flavimaculatus. Presentación de caso / Fundus flavimaculatus. Case presentation

RESUMEN Introducción: La Enfermedad de Stargardt, o fundus flavimaculatus es la distrofia macular juvenil más frecuente, responsable hasta 7 % de las distrofias maculares. Pueden ser difíciles de abordar por diversos motivos. El diagnóstico diferencial a veces es difícil, y varias de estas enfermedades producen ceguera legal a una edad relativamente joven. Objetivo: Describir el proceso diagnóstico de una entidad poco común con forma de presentación infrecuente. Presentación de caso: Se presenta el caso de una paciente de 21 años de edad, de raza blanca, con el diagnóstico de Enfermedad de Stargardt con fundus flavimaculatus. El diagnóstico se realizó teniendo en consideración los antecedentes patológicos personales, el examen físico mediante la oftalmoscopía directa e indirecta, la agudeza visual sin y con corrección, test de visión al color, angiografía fluoresceínica, tomografía de coherencia óptica (OCT) y electroretinograma. Se realizó una investigación de dicho tema por lo poco frecuente que resultan estas dos variantes de una misma enfermedad en la primera década de la vida. Conclusiones: La mayoría de las distrofias retinianas tiene desde el punto de vista clínico sus semejanzas, en cambio su evolución y pronóstico pueden ser diferentes.

ABSTRACT Introduction: Stargardt´s Disease or fundus flavimaculatus is the most frequent juvenile macular dystrophy that is responsible for 7 % of macular dystrophies. They can be difficult to address because of several reasons. The differential diagnosis is sometimes difficult to make and some of these diseases can cause legal blindness at a relatively young age. Objective: To describe the diagnostic process of an unusual entity with an infrequent form of presentation. Case presentation: We present a case of a 21-year-old white female patient with the diagnosis of Stargardt´s Disease with fundus flavimaculatus. The diagnosis was made taking into account personal pathological antecedents, the physical examination by direct and indirect ophthalmoscopy, assessment of visual acuity with and without correction, color vision test, fluorescein angiography, optical coherence tomography (OCT), and electroretinogram. Research on the topic was carried out because of the unusual appearance of these two variants of the same disease in the first decade of life. Conclusions: The majority of retinal dystrophies are similar from the clinical point of view; however, their evolution and prognosis can be different.

Enfermedad de Stargardt. Presentación de un caso / Stargardt´s disease. A case report

RESUMEN La enfermedad de Stargardt y el fondo flavimaculatus son variantes de una misma entidad nosológica, que constituyen la distrofia macular juvenil más frecuente, y una causa común de pérdida de visión central en adultos menores de 50 años. Se trata de una paciente femenina de 35 años con enfermedad de Stargardt, atendida en una unidad básica avanzada en salud del municipio de Vila Nova do Piauí, Brasil, que actualmente presenta baja capacidad visual. Se presenta una lesión macular localizada en la región foveal, de aspecto bronceado y pálido en la región temporal de la papila óptica. A nivel histológico, se produce un cúmulo de material tipo lipofuscina en las células del epitelio pigmentario de la retina, por la mutación del gen ABCA4. La incidencia de la enfermedad de Stargardt se sitúa alrededor de una persona afectada entre 10 000 y suele afectar a adolescentes y adultos jóvenes.

ABSTRACT Stargardt's disease and the flavimaculatus fund are variants of the same nosological entity. They constitute the most frequent juvenile macular dystrophy and common cause of central vision loss in adults under 50 years of age. A 35-year-old female patient who was diagnosed with Stargardt's disease currently suffers from low visual capacity. We present findings of a localized macular lesion in the foveal region of the bronzed and pale aspect in the temporal region of the optic papilla. At the histological level, a cluster of lipofuscin-like material is produced in the cells of the retinal pigment epithelium by the mutation of the ABCA4 gene. The incidence of Stargardt disease is around one person affected by 10,000 people and usually affects adolescents and young adults under 20 years old.

A Novel ABCA4 Mutation Associated with a Late-Onset Stargardt Disease Phenotype: A Hypomorphic Allele?

BACKGROUND: Stargardt disease (STGD) is the most common juvenile hereditary macular dystrophy. In the majority of cases, the diagnosis is made prior to 20 years of age and usually leads to loss of central vision. Late-onset STGD affects a smaller number of patients. Identifying genetic changes which could be associated with clinically important differences in severity or presentation of the disease is important for understanding the mechanisms of visual loss and for planning future therapeutic approaches. METHODS: We report a patient with the classic phenotype of STGD with late-onset mild disease exhibiting a slow clinical progression over 14 months of follow-up. RESULTS: A 37-year-old man presented with STGD and good vision of 6/24 in the right eye and of 6/6 in the left eye as well as typical electrophysiology findings. Objective and subjective visual deterioration was not noted over a period of 14 months. Macular genetic testing revealed a novel missense mutation in ABCA4 (Thr829Met) combined with Gly1961Glu, a classic STGD mutation usually associated with a moderately severe phenotype. CONCLUSIONS: It is suggested that the Thr829Met mutation could give rise to a hypomorphic allele of the ABC transporter with a resultant phenotype of comparatively mild STGD.

Stem cell therapy for retinal diseases.

In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt's dystrophy, and patients with geographic atrophy, providing good outcomes. This study's intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients' vision, and, finally, approaching future directions and challenges for the treatment of several conditions.

Enfermedad de stargardt o degeneración macular de stargardt / Stargardt disease or stargardt macular degeneration

La degeneración macular de Stargardt es considerada una enfermedad rara pues se presenta un caso por cada 10.000 personas (1).Es de transmisión hereditaria de un patrón autosómico recesivo. Está provocada por una mutación del gen ABCA4, que tiene una función transportadora a través de la membrana de las células fotorreceptoras. Hay 558 mutaciones diferentes que pue-den originar el mal (2).La enfermedad Stargardt y Fundusflavima-culatus son la misma enfermedad, siendo el segundo, un estado más avanzado de almacenamiento de lipofucsina (3).CASO CLINÍCOPaciente de 16 años de edad acude a consulta de medicina preventiva refiriendo presentar disminución de agudeza visual, antecedentes de miopía y astigmatismo con debida corrección de error refracta-rio. Actualmente presenta disminución de agudeza visual más notoria en zona central, usando así su visión periférica. Agudeza visual: 20/100. Campimetría: hay es-cotomas. Angiofluorgrafía: muestra una coroides oscura por depósitos de lipofuscina del epitelio pigmentario de la retina dando como resultado la enfermedad de Stargardt.

The Stargardt Macular degeneration is con-sidered a rare disease; one case per 10,000 people is presented. (1)It is Inheritance and it is given an autoso-mal recessive pattern. It is caused by a mu-tation of ABCA4 gene, which has a trans-port function through the membrane of the photoreceptor cells. There are 558 different mutations that can cause it. (2)The Stargardt disease and fundusflavima-culatus are the same disease, the second is a more advanced state of lipofuscin sto-rage. (3)CASE REPORTA 16 years old patient attends to the pre-ventive health referring to have a decrea-sed visual acuity, history of myopia and as-tigmatism with refractive error correction. Currently has more noticeable decrease in central visual acuity, so using your periphe-ral vision. Visual acuity 20/100 Campimetry: there is noscotoma, angiofluorgrafia: it dis-plays a dark choroid by deposits of lipofus-cin of the pigment epithelium of the retina which results the Stargardt disease.

Enfermedad de Stargardt con fondo flavimaculatus: presentación de un caso / Stargardt´s disease and fundus flavimaculatus: a case report

Se presenta el caso de un paciente de 10 años de edad, de raza blanca, masculino, con el diagnóstico de enfermedad de Stargardt con fondo flavimaculatus. El diagnóstico se realizó por los antecedentes patológicos personales y el examen físico mediante la oftalmoscopia directa e indirecta, la agudeza visual sin y con corrección, , test de visión al color y retinografía. Se realizó una investigación de dicho tema por lo poco frecuente que resultan estas dos variantes de una misma enfermedad en la primera década de la vida(AU)

The case of a patient of 10 years of age appears, of white race, masculine, with the diagnosis of disease of Stargardt with bottom flavimaculatus. The diagnosis was realized by the personal pathological antecedents and the physical examination by means of the direct and indirect ophthalmoscopy, the visual sharpness without and with correction, test of sensitivity to the resistance, test of vision to the color and retinography. An investigation of this subject by little frequent that was realized these two variants are from a same disease in the first decade of the life(AU)

Enfermedad de Stargardt con fondo flavimaculatus: presentación de un caso / Stargardt´s disease and fundus flavimaculatus: a case report

Se presenta el caso de un paciente de 10 años de edad, de raza blanca, masculino, con el diagnóstico de enfermedad de Stargardt con fondo flavimaculatus. El diagnóstico se realizó por los antecedentes patológicos personales y el examen físico mediante la oftalmoscopia directa e indirecta, la agudeza visual sin y con corrección, , test de visión al color y retinografía. Se realizó una investigación de dicho tema por lo poco frecuente que resultan estas dos variantes de una misma enfermedad en la primera década de la vida.

The case of a patient of 10 years of age appears, of white race, masculine, with the diagnosis of disease of Stargardt with bottom flavimaculatus. The diagnosis was realized by the personal pathological antecedents and the physical examination by means of the direct and indirect ophthalmoscopy, the visual sharpness without and with correction, test of sensitivity to the resistance, test of vision to the color and retinography. An investigation of this subject by little frequent that was realized these two variants are from a same disease in the first decade of the life.

Estudio de una familia de la Policlínica Máximo Gómez donde tres miembros padecen enfermedad de Stargardt / A Study of a Family with Stargardt`s Disease Máximo Gómez Polyclinic

Se realizó un estudio descriptivo de una familia en la cual hay un miembro afectado con la enfermedad de Stargardt en el área de salud de la Policlínica Máximo Gómez en la etapa comprendida noviembre 2004 a mayo 2006. Fueron examinados 14 familiares y 5 de ellos ínterconsultados con el grupo multidisciplinario del Centro de Retinosis Pigmentaria donde fueron diagnosticados dos enfermos más, de 8 y 12 años. El enfermo estuvo desvinculado de la consulta cuatro años y se logró su reincorporación. Se demostró una vez más la importancia que juega el médico de la familia en el diagnóstico precoz de las enfermedades, así como la vinculación estrecha entre atención secundaria y primaria en la labor de pesquisa de las enfermedades oculares...(AU)

A descriptive study on Stargart`s disease at Màximo Gòmez Polyclinic area from November 2004 and May 2006, due to the visual deficit that this illness produces was carried out . The study was done in a patient with this diagnosis. 14 relatives were examinated and 5 of them were attended by the integrated multidisciplinary group at Retinitis Pigmentosa Center to confirm the diagnosis. The patient had been away from the consultation during 4 years. Two of them who were 8 and 12 years were diagnosed with this disease. The importance of the family doctor in the early diagnosis of the diseases was also proved, as well as the close relation between primary care and secondary care for the study of new cases...(AU)