Photosensitivity and filter efficacy in albinism✰.

PURPOSE: To describe the prevalence and severity of photosensitivity in patients with albinism, and to compare with ocular features and how this correlated with use and choice of optical filters. METHODS: Cross-sectional study on 81 participants with ocular or oculocutaneous albinism. An ophthalmic evaluation including visual acuity, contrast sensitivity and evaluation of iris translucency and fundus hypopigmentation was performed. Participants were offered optical rehabilitation with testing of a wide panel of filters. The associations between ocular characteristics, subjective photosensitivity complaints, and filter choice were evaluated. RESULTS: Photosensitivity was rated as "some" to "worst imaginable" in 77.8% of participants. Severity of photosensitivity correlated significantly with fundus hypopigmentation (p = 0.04) but not with iris translucency (p = 0.14) and it was worse in those with poor visual acuity but there was no association between photosensitivity and contrast vision. Seventy-four new pairs of spectacles were prescribed in the study. All outdoor spectacles contained a filter, whereas 26.5% of new indoor spectacles did not. Relatively neutral filter colors (gray, brown or a combination of gray and brown with other colors) and low transmission were preferred. DISCUSSION: Photosensitivity is common in albinism, but research targeting treatment is limited. Color and neutral filters with a low light transmission were preferred, with participants having a large number of spectacles, presumably to meet their needs in different situations.

Visuo-spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments.

The 5xFAD mouse model of Alzheimer's disease (AD) rapidly develops AD-related neuro-behavioral pathology. Learning and memory impairments in 5xFAD mice, however, are not always replicated and the size of impairments varies considerably across studies. To examine possible sources of this variability, we analyzed the effects of age, sex, albinism due to background genes (Tyrc , Oca2p ) and motor impairment on learning and memory performance of wild type and 5xFAD mice on the Morris water maze, from 3 to 15 months of age. The 5xFAD mice showed impaired learning at 6-9 months of age, but memory impairments were not detected with the test procedure used in this study. Performance of 5xFAD mice was profoundly impaired at 12-15 months of age, but was accompanied by slower swim speeds than wild-type mice and a frequent failure to locate the escape platform. Overall female mice performed worse than males, and reversal learning impairments in 5xFAD mice were more pronounced in females than males. Albino mice performed worse than pigmented mice, confirming that albinism can impair performance of 5xFAD mice independently of AD-related transgenes. Overall, these results show that 5xFAD mice have impaired learning performance at 6-9 months of age, but learning and memory performance at 12-15 months is confounded with motor impairments. Furthermore, sex and albinism should be controlled to provide an accurate assessment of AD-related transgenes on learning and memory. These results will help reduce variability across pre-clinical experiments with 5xFAD mice, and thus enhance the reliability of studies developing new therapeutics for AD.

Acquired hemophilia A and delta storage pool deficiency in a patient with indolent non-Hodgkin lymphoma.

B-cell lymphoproliferative diseases may be associated with acquired hemostasis disorders, such as acquired hemophilia A (AHA) caused by autoantibodies that neutralize factor VIII activity, and δ-storage pool deficiency, an abnormality of platelet function due to defective dense granules and impaired secretion. We describe the case of a 67-year-old man in whom these two acquired bleeding disorders were concomitantly present as the first clinical manifestation of an indolent non-Hodgkin lymphoma. Immunosuppressive therapy with prednisone was initially started to eradicate anti-FVIII antibodies, subsequently boosted with cyclophosphamide and rituximab, these medications being also chosen to treat the associated indolent lymphoma. Bleeding symptoms were first tackled with limited benefit by using rFVIIa and then rescued using recombinant porcine FVIII. After a 6 month's follow-up lymphoma and AHA were in remission and platelet function was improved. This case underlines the need of multiple and complex diagnostic and therapeutic approaches to rare acquired bleeding disorders associated with lymphoproliferative diseases.

Skin cancers in people with albinism in Togo in 2019: results of two rounds of national mobile skin care clinics.

BACKGROUND: In people with albinism (PWA), the deficiency of melanin increase the risk of skin cancers. The aim of this study was to determine the prevalence of skin cancers and characteristics of these detected skin cancers (histological types, localization) in PWA in 10 cities in Togo in 2019. METHODS: This is a cross-sectional study of medical records of PWA systematically examined during two mobile skin care clinics in 2019, as part of a programme for the prevention and management of skin cancers in these subjects. RESULTS: During the study period, 280 (95.2%) of the 294 PWA consulted, had developed skin lesions. Of the 280 PWA, the pathological reports from the medical records of 33 patients (11.8%; (95%CI = [8.2-16.2]) had concluded to non-melanoma skin cancers. The mean age of these 33 patients was 38.6 ± 15.2 years and the sex-ratio was 1. Their occupations were mainly resellers (21.2%), traders (15.2%) and farmers (12.2%). In the 33 patients, 54 cases of non-melanoma skin cancers were identified, with some patients having more than one tumor, and some of them having more than one (histologically confirmed) diagnosis. These 54 non-melanoma skin cancers were divided into 21 cases of invasive squamous cell carcinomas, 2 cases of Bowen's disease and 31 cases of basal cell carcinomas. These non-melanoma skin cancers mainly occurred in the head and neck (33 cases; 61.1%), the upper limbs (15 cases; 27, 8%) and the trunk (4 cases; 7.4%). CONCLUSION: The results of this study show a high prevalence of skin cancers among PWAs in Togo in 2019, only non-melanoma skin cancers. In addition, they illustrate the role of ultraviolet rays with regard to the localization of skin cancers and the occupations of patients. Popularization and compliance with photo protection measures, systematic and regular examination of the skin of these PWAs will allow early detection and treatment of these skin cancers.

Ocular findings of albinism in DYRK1A-related intellectual disability syndrome.

BACKGROUND: Pathogenic variants in DYRK1A are associated with DYRK1A-related intellectual disability syndrome (DIDS). Common features of this diagnosis include microcephaly, intellectual disability, speech impairment, and distinct facial features. Reported ocular features include deep-set eyes, myopia, and strabismus. We present a case of DYRK1A-related intellectual disability syndrome with ocular findings of albinism and explore the possible pathogenesis of this previously unreported manifestation. MATERIALS AND METHODS: This is a single, retrospective case report of a child with DIDS who underwent an ophthalmic exam including detailed visual electrophysiology. Results: A 21-month-old female with microcephaly, failure to thrive, language delay, cleft palate, and cardiac defects had an ophthalmic exam showing myopia, strabismus, a hypopigmented fundus and crossed asymmetry on visual evoked potential (VEP), consistent with ocular findings of albinism. Whole exome sequencing identified a pathogenic DYRK1A variant; no albinism gene variants were reported. Her constellation of features is consistent with a diagnosis of DYRK1A-related intellectual disability syndrome; however, ocular features of albinism have not previously been reported in this condition. CONCLUSIONS: This is, to the best of our knowledge, the first report of ocular findings of albinism in a case of DYRK1A-related intellectual disability syndrome. We propose that ocular albinism is a novel ocular phenotype of DYRK1A-related disease. Ophthalmic exams in patients with this diagnosis should include thorough evaluation for ocular albinism, including VEPs.

Dermatological and Epidemiological Profiles of Patients with Albinism in São Paulo, Brazil, between 2010 and 2017: A Cross-Sectional Study.

INTRODUCTION: Oculocutaneous albinism is an autosomal recessive disease caused by complete absence of or decrease in melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at greater risk of actinic damage and skin cancer. There are no epidemiological data on the incidence of albinism in Brazil. OBJECTIVE: To analyze the clinical and epidemiological profile of patients with albinism treated by the Pró-Albino Program of the Dermatology Clinic of Santa Casa de Misericórdia from its beginning in 2010 until 2017. METHODS: In this cross-sectional study, the records of all consecutive albino patients admitted to the service in the study period were reviewed. Sociodemographic data, family history, and dermatological clinical data were collected. RESULTS: Between March 2010 and April 2017, 191 patients were admitted, of whom 109 were female (57.07%) and the age range was 0-92 years, with >30% under the age of 18 years. Consanguinity among the parents was confirmed by 26% of the patients. Unprotected sun exposure was reported by 109 (57.07%), and 138 (72.25%) had a history of sunburn. Of the 146 records with information, 38 had skin cancer (26%), with a mean age of 47.4 (p < 0.0001); the youngest patient diagnosed with a cutaneous tumor was 23 years old. The prevalence of actinic damage was high. There was information on solar elastosis and actinic keratosis in 148 medical records, of which 96 (64.8%) patients had elastosis and 75 (50.67%) keratoses. Elastosis, keratosis, and skin cancer were significantly associated with age, unprotected sun exposure, and sunburn (p < 0.05). Of the 37 (26% of the sample of 146) patients with a previous or current history of skin cancer, it was possible to identify the histological type in 29 (13 men and 16 women); of these, 18 (62%) were basal cell carcinomas (BCC), 15 (51%) were squamous cell carcinomas (SCC), and 2 (7%) were melanomas. Of these, 4 cases (14%) presented the 2 types of carcinoma (BCC and SCC), and the 2 that had a diagnosis of melanoma also had BCC. Some patients had multiple ulcerated tumors. The tumor site was preferentially in the head and neck (43%), trunk (37%) and limbs (20%). CONCLUSIONS: Albinos represent a risk group for skin cancer and other actinic lesions. These lesions were found to be prevalent in the albinos seen by the program and probably reflect the characteristics found in the Brazilian albino population. Access to health care, especially through multidisciplinary programs that enable the diagnosis and early treatment of these lesions, health education, and the use of photoprotective measures can reduce morbidity and mortality and improve the quality of life of patients with this rare genetic condition.

Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors.

Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.

Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors

Abstract Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.

Interocular transfer of visual memory - Influence of visual impairment and abnormalities of the optic chiasm.

Due to an increased crossing of the optic nerve fibers at the optic chiasm in albinism, the visual cortex receives largely monocular input from the contralateral eye. Here we investigated whether this obstruction of binocular integration at the cortical input stage also impacts on interocular information exchange at the high processing level of visual memory. Interocular transfer (IOT) of visual memory retrieval was tested psychophysically after monocular encoding in 8 albinotic participants and 24 healthy controls. The retrieval performance (hit rate, reaction time, d') was determined when using the same or different eye at encoding. To assess the effect of reduced visual acuity (VA) on recognition, we simulated interocular acuity differences (IOA) in two healthy control groups (each n = 8), i.e., with large (VA: 0.89 vs. 0.12) and small simulated interocular difference (VA: 0.25 vs. 0.12), with the latter matched to that observed in the albinotic participants (VA: 0.20 vs. 0.15). A significant decrease in retrieval performance was observed in controls with simulated strongly reduced VA in one eye (p < 0.0001). For the other conditions and groups, including the albinotic participants, no dependence on VA and no significant difference between using the same or different eye was observed. This indicates interocular transfer and hence interocular information exchange in human albinism. These findings thus provide insights into the scope of plasticity of binocular information processing and inter-hemispherical information flow.

Crohn's-like acute severe colitis associated with Hermansky-Pudlak syndrome: A case report.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage pool deficiency and systemic complications associated with ceroid deposition in the reticuloendothelial system. HPS types 1 and 4 are associated with Crohn's disease (CD)-like gastrointestinal disorders, such as granulomatous enterocolitis or perianal disease. Cases of colitis can be particularly severe and, before the use of anti-tumor necrosis factor alpha (TNFα) therapy had become common, were reported as showing poor responsiveness to medical treatment. CASE SUMMARY: We present the case of a 51-year-old albino woman who presented with acute severe colitis that led to the diagnosis of HPS. Histologic findings of biopsy samples showed chronic inflammation with deep ulcerations, and granulomas without caseous necrosis. Molecular genetic analysis confirmed HPS type 1, with a homozygous 27 base-pair deletion in exon 20 of the HPS1 gene. Once the patient's bleeding diathesis was corrected by platelet transfusion, the granulomatous colitis responded dramatically to a medical treatment regimen that included corticosteroids, azathioprine and infliximab; this regimen is similar to that used in CD treatment. Although it remains unclear if the granulomatous enterocolitis in HPS is due to ceroid deposition or reflects the co-existence of CD and HPS, the fact that this case of HPS-related granulomatous colitis responded to the same therapeutic approach used in CD suggests that this type of colitis may result from HPS patients' genetic susceptibility to CD. CONCLUSION: We report a case of severe colitis that led to the diagnosis of HPS, which was responsive to azathioprine and infliximab.

Accommodation and near visual function in children with albinism.

PURPOSE: Albinism degrades visual function due to developmental disorders of the eye and visual pathways, larger refractive errors, absent binocularity and poor fixation control. Reading spectacles is commonly prescribed in our clinic and well tolerated. The purpose was to evaluate whether the accommodative response is typical or affected in comparison to a reference group. METHODS: Twenty-two children with albinism (median: 13.5 years) and 12 controls (median: 13 years) underwent a full optometric examination and an objective accommodation measurement (WAM-5500 @ 6 Hz; Grand Seiko) in response to minus-lens-blur (-1, -2 and -3 D) and to a prolonged near viewing task (20 cm) for 5 min. RESULTS: Children with albinism displayed less accommodation to minus lens-blur and during sustained near viewing (p < 0.001) compared to the reference group. Higher visual acuity correlates with a better accommodative response (r ≥ 0.5; p ≤ 0.04). The subjective and objective measures of accommodation did not correlate. The habitual reading distance was always closer than the point towards which the subjects with albinism seemed to accommodate according to the measurements at 20 cm. CONCLUSION: Children with albinism benefits from reading spectacles due to a combination of close habitual reading distance and a poor accommodation. Objective recording of accommodation is not critical for a correct judgement of near visual function. Children already wearing reading spectacles were those with least accommodative response.

Dicas em saúde: Albinismo

Informações de utilidade pública sobre doenças, prevenção de acidentes, cuidados com a higiene, entre outros.

Hermansky-Pudlak Syndrome.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS-1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical, radiologic, and histologic features found in idiopathic pulmonary fibrosis, but occurs at a younger age. Despite knowledge of the underlying genetic defects, there are currently no definitive therapeutic or preventive approaches for HPS pulmonary fibrosis other than lung transplant.

Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959;14(2):162-169.

This landmark article by Frantisek Hermansky and Paulus Pudlak, clinicians in Prague, Czechoslovakia, is the first to describe 2 unrelated individuals with what is now called Hermansky-Pudlak syndrome, a bleeding disorder that occurs in association with oculocutaneous albinism. The definition of this syndrome resulted not only in improved care of these patients but also in a functional and molecular understanding of the disease and the role of dense granule secretion in platelet function. Hermansky-Pudlak syndrome is now known to be related to defective dense granule biogenesis due to mutations in any of ≥9 different genes.

Síndrome de Chediak-Higashi: microscopia óptica del pelo / Chediak-Higashi syndrome: Optical microscopy of hair

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Loss of binocular vision as direct cause for misrouting of temporal retinal fibers in albinism.

In humans, the nasal retina projects to the contralateral hemisphere, whereas the temporal retina projects ipsilaterally. The nasotemporal line that divides the retina into crossed and uncrossed parts coincides with the vertical meridian through the fovea. This normal projection of the retina is severely altered in albinism, in which the nasotemporal line shifted into the temporal retina with temporal retinal fibers cross the midline at the optic chiasm. This study proposes the loss of binocular vision as direct cause for misrouting of temporal retinal fibers and shifting of the nasotemporal line temporally in albinism. It is supported by many observations that clearly indicate that loss of binocular vision causes uncrossed retinal fibers to cross the midline. This hypothesis may alert scientists and clinicians to find ways to prevent or minimize the loss of binocular vision that may occur in some diseases such as albinism and early squint. Hopefully, this will minimize the misrouting of temporal fibers and improve vision in such diseases.