Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature.

PURPOSE: To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy. METHODS: Case report. RESULTS: A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy. CONCLUSION: BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities. ABBREVIATIONS: BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.

Diagnosis of night blindness through standardized interview and electroretinography.

INTRODUCTION: Objective: To compare the diagnosis of NB through the use of the standardized interview of the World Health Organization/Pan American Health Organization (WHO/PAHO) with electroretinography, and also to evaluate the association of these diagnoses with serum concentrations of retinol in class III obesity individuals. Methods: Adult patients of both genders, in the 20-60 age group, with BMI ≥ 40 kg/m² were studied. NB was diagnosed through electroretinography and the standardized interview validated by the WHO/PAHO. Serum level of retinol was quantified by the HPLC-UV method, and VAD was diagnosed when levels were <1.05 µmol /L, and severity was also evaluated. Statistical analysis was carried out through the Statistical Package for the Social Sciences, version 21.0 (p < 0.05). Results: Mean BMI was 44.9  11.8 kg/m², and a negative correlation was found in serum levels of retinol (p= 0.01). The prevalence of VAD, according to the serum concentrations of retinol, was 14%, and of this percentage 23.3% had NB according to the standardized interview, and 22.0% according to electroretinography. NB diagnosed by both methods showed an association with VAD according to the serum concentrations of retinol. Of these individuals with NB, according to the standardized interview, 6.9% showed severe VAD, 10.3% moderate VAD and 82.8% marginal VAD. Conclusion: The standardized interview for the diagnosis of NB can be a good strategy to evaluate the nutritional status of vitamin A, and it is a simple, non-invasive and low-cost method.

INTRODUCCIÓN: Objetivo: Comparar el diagnóstico de NB mediante el uso de la entrevista estandarizada de la Organización Mundial de la Salud/Organización Panamericana de la Salud (OMS/OPS) con electrorretinografía, y también evaluar la asociación de estos diagnósticos con las concentraciones séricas de retinol en la clase III personas obesas. Métodos: se estudiaron pacientes adultos de ambos sexos, en el grupo de 20 a 60 años de edad, con un IMC ≥ 40 kg/m². La NB se diagnosticó mediante electrorretinografía y la entrevista estandarizada validada por la OMS/OPS. El nivel sérico de retinol se cuantificó mediante el método HPLC-UV, y el DVA se diagnosticó cuando los niveles eran <1.05 µmol / L, y también se evaluó la gravedad. El análisis estadístico se realizó a través del Paquete Estadístico para las Ciencias Sociales, versión 21.0 (p <0.05). Resultados: IMC promedio fue de 44.9 ± 11.8 kg / m², y se encontró una correlación negativa en los niveles séricos de retinol (p = 0.01). La prevalencia de DVA, según las concentraciones séricas de retinol, fue del 14%, y de este porcentaje, el 23,3% tenía NB de acuerdo con la entrevista estandarizada y el 22,0% según la electrorretinografía. La NB diagnosticada por ambos métodos mostró una asociación con VAD según las concentraciones séricas de retinol. De estos individuos con NB, según la entrevista estandarizada, el 6,9% mostró VAD grave, el 10,3% de VAD moderado y el 82,8% de VAD marginal. Conclusión: la entrevista estandarizada para el diagnóstico de NB puede ser una buena estrategia para evaluar el estado nutricional de la vitamina A, y es un método simple, no invasivo y de bajo costo.

Three cases of acute-onset bilateral photophobia.

PURPOSE: To report the findings in 3 cases of bilateral negative electroretinograms (ERGs) with acute onset of photophobia. STUDY DESIGN: Retrospective case series. METHODS: The medical charts of the 3 patients were reviewed. RESULTS: A 43-year-old woman, a 68-year-old woman, and a 41-year-old woman were referred to Nagoya University Hospital. Their main symptom was bilateral acute photophobia. None of the patients had any systemic diseases or specific medical history. The decimal best-corrected visual acuity (> 0.8) and Humphrey visual fields (mean deviation > -3 dB) were relatively well preserved in all 3 patients. The optical coherence tomography (OCT) and fundus autofluorescence findings were essentially normal. Fluorescein angiography showed mild leakage in 1 patient but no abnormality in the other 2 patients. However, the ERGs of the 3 patients had the features of abnormal ERGs found in patients with incomplete congenital stationary night blindness (CSNB). Exome analyses found no pathogenic variants related to known CSNB-related genes. The symptoms and ERGs of the 3 patients have not progressed or recovered after a relatively long follow-up period. CONCLUSION: The ERG characteristics of 3 patients with bilateral photophobia were similar to those of incomplete CSNB, suggesting post-phototransductional abnormalities. The symptoms and genetic analyses indicated the possibility of an acquired condition rather than a hereditary retinal disease.

NYX mutations in four families with high myopia with or without CSNB1.

PURPOSE: Mutations in the NYX gene are known to cause complete congenital stationary night blindness (CSNB1), which is always accompanied by high myopia. In this study, we aimed to investigate the association between NYX mutations and high myopia with or without CSNB1. METHODS: Four Chinese families having high myopia with or without CSNB1 and 96 normal controls were recruited. We searched for mutations in the NYX gene using Sanger sequencing. Further analyses of the detected variations in the available family members were performed, and the frequencies of the detected variations in 96 normal controls were determined to verify our deduction. The effect of each variation on the nyctalopin protein was predicted using online tools. RESULTS: Four potential pathogenic variations in the NYX gene were found in four families with high myopia with or without CSNB1. Three of the four variants were novel (c.626G>C; c.121delG; c.335T>C). The previously identified variant, c.529_530delGCinsAT, was found in an isolated highly myopic patient and an affected brother, but the other affected brother did not carry the same variation. Further linkage analyses of this family showed a coinheritance of markers at MYP1. These four mutations were not identified in the 96 normal controls. CONCLUSIONS: Our study expands the mutation spectrum of NYX for cases of high myopia with CSNB1; however, more evidence is needed to elucidate the pathogenic effects of NYX on isolated high myopia.

Tomografía de coherencia óptica en el diagnóstico de la acromatopsia / Optical coherence tomography in the diagnosis of achromatopsia

CASO CLÍNICO: Varón de 55 años con nictalopía, fotofobia, mala visión de los colores y nistagmo. Nos planteamos el diagnóstico diferencial entre la acromatopsia y el monocromatismo de conos azules, puesto que ambos son clínicamente indistinguibles. En la tomografía de coherencia óptica (OCT) nos encontramos un patrón de reflectividad foveal característico de la acromatopsia, diagnóstico que posteriormente confirmamos con el estudio genético. DISCUSIÓN: La OCT es un método de diagnóstico por imagen, no invasivo, que permite la visualización de los tejidos con alta resolución. Su aportación en enfermedades clínicamente similares es fundamental porque nos ayuda a hacer el diagnóstico

CASE REPORT: The case of a fifty five year-old male with nyctalopia, photophobia, poor colour vision and nystagmus, is presented. The initial suspected diagnoses were achromatopsia and blue-cone monochromatism, since both are clinically indistinguishable. Optical coherence tomography (OCT) showed the characteristic foveal reflectivity pattern of achromatopsia. This diagnosis was subsequently confirmed by genetic study. DISCUSSION: OCT is a non-invasive diagnostic imaging method that allows tissue morphology to be observed with high resolution. Its use might be of great help to distinguish clinically similar diseases

Sorting out co-occurrence of rare monogenic retinopathies: Stargardt disease co-existing with congenital stationary night blindness.

BACKGROUND: Inherited retinal diseases are uncommon, and the likelihood of having more than one hereditary disorder is rare. Here, we report a case of Stargardt disease and congenital stationary night blindness (CSNB) in the same patient, and the identification of two novel in-frame deletions in the GRM6 gene. MATERIALS AND METHODS: The patient underwent an ophthalmic exam and visual function testing including: visual acuity, color vision, Goldmann visual field, and electroretinography (ERG). Imaging of the retina included fundus photography, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence. Genomic DNA was PCR-amplified for analysis of all coding exons and flanking splice sites of both the ABCA4 and GRM6 genes. RESULTS: A 46-year-old woman presented with recently reduced central vision and clinical findings of characteristic yellow flecks consistent with Stargardt disease. However, ERG testing revealed an ERG phenotype unusual for Stargardt disease but consistent with CSNB1. Genetic testing revealed two previously reported mutations in the ABCA4 gene and two novel deletions in the GRM6 gene. CONCLUSIONS: Diagnosis of concurrent Stargardt disease and CSNB was made on the ophthalmic history, clinical examination, ERG, and genetic testing. This case highlights that clinical tests need to be taken in context, and that co-existing retinal dystrophies and degenerations should be considered when clinical impressions and objective data do not correlate.

A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease.

PURPOSE: Genetic studies were performed to identify the causative mutation in a 15-year-old girl diagnosed with congenital stationary night blindness (CSNB) presenting Mizuo-Nakamura phenomenon, a typical Oguchi disease symptom. The patient also had dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE). METHODS: Mutation analysis was done by sequencing two candidate genes, S-antigen (SAG; arrestin 1), associated with Oguchi type 1, and rhodopsin kinase (GRK1), associated with Oguchi type 2. In addition, the C677T variation in the methylenetetrahydrofolate reductase (MTHFR) gene was also screened in the family, to determine its probable association with hyperhomocysteinemia in the patient. RESULTS: Sequencing of the SAG and GRK1 resulted in identifying a novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in SAG, which in unaffected siblings either was present in a heterozygous state or absent. The C677T heterozygous allele in the MTHFR gene was found to be associated with hyperhomocysteinemia in the patient and other family members. CONCLUSIONS: This is the first report of Oguchi type 1 in a Pakistani patient due to a nonsense mutation (c.916G>T; p.Glu306*) in SAG. The neurologic and hematological abnormalities likely are not associated with the SAG variant.

Thriving public-private partnership to fortify cooking oil in the West African Economic and Monetary Union (UEMOA) to control vitamin A deficiency: Faire Tache d'Huile en Afrique de l'Ouest.

BACKGROUND: In sub-Saharan Africa, more than 42% of children are at risk for vitamin A deficiency, and control of vitamin A deficiency will prevent more than 600,000 child deaths annually. In the West African Economic and Monetary Union (UEMOA), an estimated 54.3% of preschool-age children are vitamin A deficient and 13% of pregnant women have night blindness. OBJECTIVE: To project the achievements of this West African coalition. METHODS: This article documents the achievements, challenges, and lessons learned associated with the development of a public-private partnership to fortify vegetable oil in West Africa through project reports and industry assessments. RESULTS: National-level food consumption surveys identified cooking oil as a key vehicle for vitamin A. Stakeholders therefore advocated for the production of fortified vegetable oil at large scale, supported industrial assessments, and reinforced the capacity of cooking oil industries to implement vitamin A fortification through effective coordination of public and private partnerships tied with standards, regulations, and social marketing. Strong alliances for food fortification were established at the regional and national levels. Stakeholders also developed policies, adopted directives, built capacity, implemented social marketing, and monitored quality enforcement systems to sustain fortification for maximum public health impact. The synergy created resulted from the unique and complementary core competencies of all the partners under effective coordination. The initiative began with the 8 UEMOA member countries and now includes all 15 countries of the Economic Community of West African States (ECOWAS), plus Cameroon, Tanzania, and Mozambique, forming a sub-Saharan Africa-wide initiative on food fortification. All members of the Professional Association of Cooking Oil Industries of the West African Economic and Monetary Union (AIFO-UEMOA) now fortify edible oil with vitamin A. Through multisector cooperation, an estimated 70% of the population has access to vitamin A-fortified edible oil in participating countries. CONCLUSIONS: Sustainable fortification of cooking oil is now a reality in all UEMOA countries.

A novel p.Gly603Arg mutation in CACNA1F causes Åland island eye disease and incomplete congenital stationary night blindness phenotypes in a family.

PURPOSE: To report, for the first time, that X-linked incomplete congenital stationary night blindness (CSNB2A) and Åland island eye disease (AIED) phenotypes coexist in a molecularly confirmed pedigree and to present novel phenotypic characteristics of calcium channel alpha-1F subunit gene (CACNA1F)-related disease. METHODS: Two affected subjects (the proband and his maternal grandfather) and an unaffected obligate carrier (the proband's mother) underwent detailed ophthalmological evaluation, fundus autofluorescence imaging, and spectral-domain optical coherence tomography. Goldmann visual field assessment and full-field electroretinogram (ERG) were performed in the two affected subjects, and multichannel flash visual evoked potential was performed on the proband. Scotopic 15 Hz flicker ERG series were performed in both affected subjects to evaluate the function of the slow and fast rod pathways. Haplotype analysis using polymorphic microsatellite markers flanking CACNA1F was performed in all three family members. The proband's DNA was sequenced for mutations in the coding sequence of CACNA1F and nyctalopin (NYX) genes. Segregation analysis was performed in the family. RESULTS: Both affected subjects had symptoms of nonprogressive nyctalopia since childhood, while the proband also had photophobia. Both cases had a distance visual acuity of 20/50 or better in each eye, normal contrast sensitivity, and an incomplete type of Schubert-Bornschein ERGs. The proband also had high myopia, a mild red-green color deficit, hypopigmented fundus, and foveal hypoplasia with no evidence of chiasmal misrouting. Spectral-domain optical coherence tomography confirmed the presence of foveal hypoplasia in the proband. The clinical phenotype of the proband and his maternal grandfather fit the clinical description of AIED and CSNB2A, respectively. The fundus autofluorescence and the visual fields were normal in both cases; the scotopic 15 Hz flicker ERG demonstrated only fast rod pathway activity in both. Both affected cases shared the same haplotype across CACNA1F. The proband carried a novel hemizygous c.1807G>C mutation (p.G603R) in the CACNA1F gene. The change segregated with the disease phenotypes and was not identified in 360 control chromosomes. No mutations were identified in NYX. CONCLUSIONS: This report of a missense mutation in CACNA1F causing AIED and CSNB2A phenotypes in a family confirms that both diseases are allelic and that other genetic or environmental modifiers influence the expression of CACNA1F. This is the first report to suggest that in CACNA1F-related disease, the rod system activity is predominantly from the fast rod pathways.

Night blindness in a teenager with cystic fibrosis.

This article describes the case of a 16-year-old boy with cystic fibrosis who presented with difficulty seeing in the dark. He had a history of bowel surgery at birth, and he developed cystic fibrosis liver disease and osteopenia during his teenage years. He always had good lung function. When his serum vitamin A level was checked, it was undetectable in sample. He was diagnosed with night blindness and commenced on high-dose vitamin A. His symptoms resolved within 3 days. However, it took over 1 year for his vitamin A level to return to normal. This case emphasizes the importance of monitoring vitamin levels in cystic fibrosis to detect deficiency and prevent long-term consequences, and it highlights the challenges encountered during the course of night blindness treatment.

Molecular analysis of the choroideremia gene related clinical findings in two families with choroideremia.

PURPOSE: To investigate the choroideremia (CHM) gene in two families with CHM and to characterize the related clinical features. METHODS: Two families underwent complete ophthalmic examinations and three males were diagnosed with CHM. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the two families and from 100 unrelated control subjects from the same population. Exons 1-15 of CHM were amplified by PCR and directly sequenced. Ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, visual field, optical coherence tomography, electroretinogram, and Pentacam. RESULTS: The affected men were hemizygous and had night blindness, chorioretinal atrophy spreading from the posterior pole to the mid-periphery, and bareness of the sclera. A novel c.1488delGinsATAAC mutation was detected in CHM in family 1. Another mutation c.1703 C>G (S558X) within exon 14 of CHM was identified in family 2, which caused the serine 558 codon (TCA) to be changed to a stop codon (TGA). CONCLUSIONS: This study identified a novel mutation in CHM associated with CHM and its related clinical features. Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.

Oguchi disease masked by retinitis pigmentosa.

The purpose of this study was to report a patient with Oguchi disease whose ophthalmological characteristics were masked by retinitis pigmentosa (RP). The method used in this study was case report. A 53-year-old man had a progressive decrease in his visual acuity and was diagnosed with RP because of night blindness, fundoscopic findings, ring scotoma, and extinguished single-flash electroretinograms (ERGs). However, a faint golden-yellowish reflex of the retina prompted us to make a more detailed examination of the fundus after a long period of dark adaptation, ERGs, and genetic analysis. Examinations showed the Mizuo-Nakamura phenomenon, relative intact photopic ERGs, and a SAG mutation, and the patient was diagnosed with RP associated with Oguchi disease. When RP accompanies Oguchi disease, the clinical characteristics of Oguchi disease might be masked. In such a situation, the correct diagnosis is difficult. However, careful analysis of clinical findings will suggest Oguchi disease, which can be confirmed by molecular genetics.

Relationship of homestead food production with night blindness among children below 5 years of age in Bangladesh.

OBJECTIVE: To examine the relationship between homestead food production and night blindness among pre-school children in rural Bangladesh in the presence of a national vitamin A supplementation programme. DESIGN: A cross-sectional study. SETTING: A population-based sample of six rural divisions of Bangladesh assessed in the Bangladesh Nutrition Surveillance Project 2001-2005. SUBJECTS: A total of 158 898 children aged 12-59 months. RESULTS: The prevalence rates of night blindness in children among those who did and did not receive vitamin A capsules in the last 6 months were 0·07 % and 0·13 %, respectively. Given the known effect of vitamin A supplementation on night blindness, the analysis was stratified by children's receipt of vitamin A capsules in the last 6 months. Among children who did not receive vitamin A capsules in the last 6 months, the lack of a home garden was associated with increased odds of night blindness (OR = 3·16, 95 % CI 1·76, 5·68; P = 0·0001). Among children who received vitamin A capsules in the last 6 months, the lack of a home garden was not associated with night blindness (OR = 1·28, 95 % CI 0·71, 2·31; P = 0·4). CONCLUSIONS: Homestead food production confers a protective effect against night blindness among pre-school children who missed vitamin A supplementation in rural Bangladesh.

Chapter 29: historical aspects of the major neurological vitamin deficiency disorders: overview and fat-soluble vitamin A.

The vitamine doctrine: Although diseases resulting from vitamin deficiencies have been known for millennia, such disorders were generally attributed to toxic or infectious causes until the "vitamin doctrine" was developed in the early 20th century. In the late-19th century, a physiologically complete diet was believed to require only sufficient proteins, carbohydrates, fats, inorganic salts, and water. From 1880-1912, Lunin, Pekelharing, and Hopkins found that animals fed purified mixtures of known food components failed to grow or even lost weight and died, unless the diet was supplemented with small amounts of milk, suggesting that "accessory food factors" are required in trace amounts for normal growth. By this time, Funk suggested that deficiencies of trace dietary factors, which he labeled "vitamines" on the mistaken notion that they were "vital amines," were responsible for such diseases as beriberi, scurvy, rickets, and pellagra. Vitamin A deficiency eye disease: Night blindness was recognized by the ancient Egyptians and Greeks, and many authorities from Galen onward advocated liver as a curative. Outbreaks of night blindness were linked to nutritional causes in the 18th and 19th centuries by von Bergen, Schwarz, and others. Corneal ulceration was reported in 1817 by Magendie among vitamin A-deficient dogs fed for several weeks on a diet limited to sugar and water, although he erroneously attributed this to a deficiency of dietary nitrogen (i.e. protein). Subsequently, corneal epithelial defects, often in association with night blindness, were recognized in malnourished individuals subsisting on diets now recognizable as deficient in vitamin A by Budd, Livingstone, von Hubbenet, Bitot, Mori, Ishihari, and others. During World War I, Bloch conducted a controlled clinical trial of different diets among malnourished Danish children with night blindness and keratomalacia and concluded that whole milk, butter, and cod-liver oil contain a fat-soluble substance that protects against xerophthalmia. Early retinal photochemistry: In the 1870s, Boll found that light causes bleaching of the retinal pigment, and suggested that the outer segments of the rods contain a substance that conveys an impression of light to the brain by a photochemical process. Shortly thereafter, Kühne demonstrated that the bleaching process depends upon light, and was reversible if the retinal pigment epithelium was intact. Kühne proposed an "optochemical hypothesis," a prescient concept of photochemical transduction, attributing vision to a photochemical change in visual purple (rhodopsin) with resulting chemical products stimulating the visual cells and thereby conveying a visual image. Vitamin A: In 1913, Ishihara proposed that a "fatty substance" in blood is necessary for synthesis of both rhodopsin and the surface layer of the cornea, and that night blindness and keratomalacia develop when this substance is deficient. That year McCollum and Davis (and almost simultaneously Mendel and Osborne) discovered a fat-soluble accessory food factor (later called "fat-soluble A") distinct from the water-soluble anti-beriberi factor (later called "fat-soluble B"). By 1922 McCollum and colleagues distinguished two vitamins within the fat-soluble fraction, later named vitamins A and D. In 1925 Fridericia and Holm directly linked vitamin A to night blindness in animal experiments using rats, and in 1929 Holm demonstrated the presence of vitamin A in retinal tissue. In the 1930s, Moore, Karrer, Wald, and others established the provitamin role of beta-carotene. Karrer and colleagues isolated beta-carotene (the main dietary precursor of vitamin A) and retinol (vitamin A), and determined their chemical structures. In 1947, Isler and colleagues completed the full chemical synthesis of vitamin A. Modern retinal photochemistry: Beginning in the 1930s, Wald and colleagues greatly elaborated the photochemistry of vision, with the discovery of the visual cycle of vitamin A, demonstration that rhodopsin is decomposed by light into retinal (the aldehyde form of vitamin A) and a protein (opsin), elaboration of the enzymatic conversions of various elements in the rhodopsin system, and discovery that the rhodopsin system is dependent on a photoisomerization of retinal. In 1942, Hecht and colleagues demonstrated that a single photon could trigger excitation in a rod. In 1965, Wald suggested that a large chemical amplification was necessary for this degree of light sensitivity, likely by a cascade of enzymatic reactions. Later studies elaborated this cascade and found that an intermediary in the photoisomerization of retinal interacts with transducin, a G-protein, to activate phosphodiesterases that control cyclic GMP levels, which in turn modulate the release of neurotransmitter from the rod cell. Public health: Although the availability of vitamin A through food fortification and medicinal supplements virtually eliminated ocular vitamin A deficiency from developed countries by the second half of the 20th century, vitamin A deficiency remains a serious problem in developing countries as indicated by global surveys beginning in the 1960s. Millions of children were shown to be vitamin A deficient, with resultant blindness, increased susceptibility to infection, and increased childhood mortality. Beginning in the 1960s, intervention trials showed that vitamin A deficiency disorders could be prevented in developing countries with periodic vitamin A dosing, and in the 1980s and 1990s, large randomized, double-blind, placebo-controlled clinical trials demonstrated the marked efficacy of vitamin A supplementation in reducing childhood mortality.

Maternal night blindness during pregnancy is associated with low birthweight, morbidity, and poor growth in South India.

Maternal night blindness is common during pregnancy in many developing countries. Previous studies have demonstrated important consequences of maternal night blindness during pregnancy on the health of the mother and newborn infant. We compared birthweight, 6-mo infant mortality, morbidity, and growth among infants of women who did and did not report a history of night blindness from a community-based, randomized trial of newborn vitamin A supplementation in south India. Birthweight was measured within 72 h of delivery. Infants were followed until 6 mo of age for mortality and morbidity was assessed at household visits every 2 wk. Anthropometry was assessed at 6 mo of age. A total of 12,829 live-born infants were included, 680 of whom were infants of mothers with night blindness during the index pregnancy. Maternal night blindness was associated with an increased risk of low birthweight in a dose-dependent fashion based on birthweight cut-offs: <2500 g, adjusted relative risk (RR) = 1.13 (95% CI = 1.01, 1.26); <2000 g, adjusted RR = 1.70 (95% CI = 1.27, 2.26); <1500 g, adjusted RR = 3.38 (95% CI = 1.18, 6.33); with an increased risk of diarrhea (adjusted RR = 1.16, 95% CI = 1.03, 1.30), dysentery (adjusted RR = 1.25, 95% CI = 1.03, 1.53), acute respiratory illness (adjusted RR = 1.32, 95% CI = 1.21, 1.44), and poor growth at 6 mo; underweight (adjusted RR = 1.14, 95% CI = 1.02, 1.26), stunting (adjusted RR = 1.19, 95% CI = 1.05, 1.34). Maternal night blindness was not associated with 6-mo infant mortality or wasting at 6 mo. This study demonstrates that there are important consequences to the infant of maternal vitamin A deficiency during pregnancy.