Reading skills in children and adults with albinism: the role of visual impairment.

PURPOSE: To evaluate whether visual impairment in albinism contributes significantly to the acquisition of normal reading skills. METHODS: The authors administered standardized reading tests to 41 children and 18 adults with albinism. The Young Children's Achievement Test was used for children between 4 and 6 years old and the Woodcock-Johnson III was used for children 7 years and older and adults. Parents of children and adult subjects also completed a questionnaire to document developmental, academic, and/or work experiences. The Spearman test was used to evaluate the relationship between binocular best-corrected visual acuity (BCVA) and reading test results. RESULTS: Standardized reading tests in both children and adults with albinism showed a normal distribution of scores. BCVA did not appear to play a significant role in the development of normal reading ability in these individuals who were visually impaired except for a mild correlation of decreased reading fluency on the Woodcock-Johnson III with decreased BCVA (r = 0.287, P = .046). Many young children with albinism had superior reading skills despite having a BCVA of 20/200 or worse (legal blindness). CONCLUSION: This study of cognitively normal children and adults with albinism demonstrates that impaired vision during childhood does not by itself significantly impede a child's ability to acquire normal reading skills. However, the lower reading fluency that occurs in the more visually impaired individuals suggests they would benefit, both in the school system and workplace, with an accommodation involving more time to complete reading tasks.

Reading acuity in albinism: evaluation with MNREAD charts.

INTRODUCTION: The MNREAD reading acuity (RA) charts use continuous-text reading to measure (1) RA, ie, the smallest size of print that the patient can resolve; (2) maximum reading speed (MRS); and (3) critical print size (CPS), ie, the smallest print that the patient can read with maximum speed. This project used the MNREAD charts to evaluate reading performance in children and adults with albinism to determine the smallest print size recommended to facilitate effortless reading. METHODS: A total of 63 subjects with albinism were administered the MNREAD test to determine the critical print size for effortless reading. The subjects read continuous, high-contrast text print until they could no longer discern the words. The MRS and CPS were determined with the MNREAD protocol. Presence or absence of nystagmus and strabismus was recorded. Distance visual acuity was measured with ETDRS charts. RESULTS: The sample included 25 male and 38 female subjects with a median age of 16 years. Median MRS was 150 words per minute. The mean CPS was 0.84 logMAR, notably larger than the mean RA of 0.53 logMAR. CONCLUSIONS: The MNREAD acuity charts can be used to determine functional reading ability and critical print size for effortless reading in individuals with albinism. The amount of enlargement in print size can be used in educational and vocational recommendations to facilitate reading.

Inactivation of Mycobacterium tuberculosis mannosyltransferase pimB reduces the cell wall lipoarabinomannan and lipomannan content and increases the rate of bacterial-induced human macrophage cell death.

The Mycobacterium tuberculosis (M.tb) cell wall contains an important group of structurally related mannosylated lipoglycans called phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM), and mannose-capped lipoarabinomannan (ManLAM), where the terminal alpha-[1-->2] mannosyl structures on higher order PIMs and ManLAM have been shown to engage C-type lectins such as the macrophage mannose receptor directing M.tb phagosome maturation arrest. An important gene described in the biosynthesis of these molecules is the mannosyltransferase pimB (Rv0557). Here, we disrupted pimB in a virulent strain of M.tb. We demonstrate that the inactivation of pimB in M.tb does not abolish the production of any of its cell wall mannosylated lipoglycans; however, it results in a quantitative decrease in the ManLAM and LM content without affecting higher order PIMs. This finding indicates gene redundancy or the possibility of an alternative biosynthetic pathway that may compensate for the PimB deficiency. Furthermore, infection of human macrophages by the pimB mutant leads to an alteration in macrophage phenotype concomitant with a significant increase in the rate of macrophage death.

Evaluation of vision-specific quality-of-life in albinism.

INTRODUCTION: Human albinism is a genetic condition associated with visual impairment that affects many aspects of daily life. Office measurements of visual acuity do not necessarily reflect daily visual function and health status. This study used the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to determine the effect of albinism-associated ophthalmopathy on quality of life (QOL). METHODS: We administered the NEI-VFQ, which consists of 25 questions about QOL (VFQ-25) and 14 questions about well-being (VFQ-39), to 44 consenting participants with albinism older than the age of 18 years. RESULTS: Nineteen male and 25 female subjects completed the study. Median age was 30.5 years (range, 18-79 years). Mean best-corrected visual acuity was 20/83 (range, 20/20 to 20/320). Forty-eight percent reported that they were currently able to drive with their condition. Participants perceived midscale problems with their general vision (median subscale score 60.0). Visual acuity correlated moderately with overall NEI-VFQ composite scores (r(s) = 0.40, p = 0.01 for VFQ-25 and r(s) = 0.36, p = 0.02 for VFQ-39). Most notable impairment was recorded for distance acuity, vision-specific mental health, and vision-specific role difficulties (VFQ-39 median subscale scores 66.7, 70.0, and 75.0, respectively). Differences by sex were insignificant. Greater ceiling effects were noted for the VFQ-25 than for the VFQ-39. CONCLUSIONS: The NEI-VFQ-39 is a method to evaluate self-reported effects of vision-related QOL in albinism and may be used as a baseline for evaluating outcomes in interventional studies in these patients.

Neurodevelopment in children with albinism.

OBJECTIVES: To evaluate neurologic development in children with albinism. DESIGN: Observational cohort series. PARTICIPANTS AND/OR CONTROLS: Seventy-eight children with albinism, ages 4 to 18 years. METHODS: Parents completed a developmental questionnaire and were interviewed to evaluate their child for attention deficit hyperactivity disorder (ADHD) utilizing Diagnostic and Statistical Manual IV criteria. Sixty-five children underwent neurologic evaluation of balance and fine and gross motor movements. Results were compared with age-appropriate norms. Standardized reading tests were administered to 44 children. Each of 7 neurodevelopmental parameters were compared in terms of binocular best-corrected visual acuity (BCVA) using the nonparametric Wilcoxon rank-sum test. MAIN OUTCOME MEASURES: Seven neurodevelopmental parameters were measured, including onset of walking, tandem gait, repetitive finger movements, sequential finger movements, standing on one foot, hopping on one foot, and throwing a ball overhand. School performance, reading performance, and presence of ADHD were also measured. RESULTS: The BCVA ranged from 20/20 to 20/800, with median of 20/150. A diagnosis of ADHD was present in 21.8% and pervasive developmental disorder was noted in three children (3.8%). No significant developmental delays were noted in the majority of children. Motor development was generally within the normal range and unaffected by severity of visual impairment. Parents reported that 82% performed at grade level in math and 74% at grade level in reading. Only 18% scored below average on standardized reading tests. CONCLUSIONS: Most children with albinism have normal neurologic development despite visual impairment and increased prevalence of ADHD.

Sectoral iris heterochromia and retinal pigment variation in 13q-syndrome.

Chromosome 13q deletion syndrome is characterized by growth retardation, cognitive delays, and organ and musculoskeletal deformities. Typical ocular associations include retinoblastoma, microphthalmia, and colobomas. We report a case of bilateral iris heterochromia and retinal pigment abnormalities in a child with 13q-syndrome.

The prevalence of attention-deficit/hyperactivity disorder among persons with albinism.

Attention-deficit/hyperactivity disorder (ADHD) is a common diagnosis in children and adults. Human albinism is an uncommon genetic condition associated with visual impairment that may affect behavior. To determine if there is a relationship between albinism and ADHD, the prevalence of ADHD was examined among 78 children (age range, 4-18 years) and among 44 adults (age range, 19-79 years) with ocular or oculocutaneous albinism. ADHD was diagnosed in the pediatric population using a combination of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria, Conners' Parent Rating Scale, and physician observation. Adults were diagnosed using the Utah criteria for ADHD as confirmed by physician history and interview. Seventeen children (22.7% [17 of 75]) (3 children with existing diagnoses of pervasive developmental disorder were identified but were not included in the data analysis) and 3 adults (6.8%) met the criteria for ADHD. The combined hyperactivity and impulsivity subtype of ADHD was most common, accounting for 50% of the diagnoses. Binocular best-corrected visual acuity and genetic type of albinism were not found to correlate with a diagnosis of ADHD. The prevalence of ADHD among children and adults with albinism is more frequent than that reported among the general population and is not related to binocular best-corrected visual acuity.

Overexpression of Mycobacterium tuberculosis manB, a phosphomannomutase that increases phosphatidylinositol mannoside biosynthesis in Mycobacterium smegmatis and mycobacterial association with human macrophages.

Mycobacterium tuberculosis (M. tb) pathogenesis involves the interaction between the mycobacterial cell envelope and host macrophage, a process mediated, in part, by binding of the mannose caps of M. tb lipoarabinomannan (ManLAM) to the macrophage mannose receptor (MR). A presumed critical step in the biosynthesis of ManLAM, and other mannose-containing glycoconjugates, is the conversion of mannose-6-phosphate to mannose-1-phosphate, by a phosphomannomutase (PMM), to produce GDP-mannose, the primary mannose-donor in mycobacteria. We have identified four M. tb H37Rv genes with similarity to known PMMs. Using in vivo complementation of PMM and phosphoglucomutase (PGM) deficient strains of Pseudomonas aeruginosa, and an in vitro enzyme assay, we have identified both PMM and PGM activity from one of these genes, Rv3257c (MtmanB). MtmanB overexpression in M. smegmatis produced increased levels of LAM, lipomannan, and phosphatidylinositol mannosides (PIMs) compared with control strains and led to a 13.3 +/- 3.9-fold greater association of mycobacteria with human macrophages, in a mannan-inhibitable fashion. This increased association was mediated by the overproduction of higher order PIMs that possess mannose cap structures. We conclude that MtmanB encodes a functional PMM involved in the biosynthesis of mannosylated lipoglycans that participate in the association of mycobacteria with macrophage phagocytic receptors.

Mycobacterium tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcgammaRII and the mannose receptor.

The entry of Mycobacterium tuberculosis (Mtb) into the host macrophage and its survival in this environment are key components of tuberculosis pathogenesis. Following intracellular replication of the bacterium within alveolar macrophages, there is spread of bacilli to regional lymph nodes in the lungs and subsequent presentation of antigens to the host immune system. How this process occurs remains poorly understood, but one mechanism may involve the migration of macrophages containing Mtb across the alveoli to lymph nodes, where there is development of a protective host response with formation of granulomas composed in part of aggregated and fused, apoptotic, infected macrophages. Leukocyte integrins, including lymphocyte function-associated antigen-1 (LFA-1) and complement receptors CR3 and CR4, and their counter receptors play a major role in macrophage adhesion processes and phagocytosis. In this study, the appearance of Mtb-infected macrophages over time was examined, using inverted-phase microscopy and an in vitro culture model of human monocyte-derived macrophages (MDMs). Prior to and immediately following infection of the MDMs with Mtb, the macrophages appeared as individual cells in monolayer culture; however, within 24 h of infection with Mtb, the MDMs began to migrate and adhere to each other. The kinetics of this response were dependent on both the m.o.i. and the length of infection. Quantitative transmission electron microscopy studies revealed that macrophage adhesion was accompanied by increases in levels of LFA-1 and its counter receptor (ICAM-1), decreases in surface levels of the phagocytic receptors CR3, CR4 and FcgammaRII, and an increase in major histocompatibility complex Class II (MHC-II) molecules at 72 h post-infection. Decreases in surface levels of CR3 and CR4 had a functional correlate, with macrophages containing live bacilli showing a diminished phagocytic capacity for complement-opsonized sheep erythrocytes; macrophages containing heat-killed bacilli did not show this diminished capacity. The modulation of macrophage adhesion and phagocytic proteins may influence the trafficking of Mtb-infected macrophages within the host, with increases in levels of LFA-1 and ICAM-1 enhancing the adhesive properties of the macrophage and decreases in phagocytic receptors diminishing the phagocytic capacity of an already-infected cell, potentially allowing for maintenance of the intracellular niche of Mtb.