Dietary Deficiency Of Vitamin Research Articles

Vitamin K Status Influences Brain Sulfatide Metabolism in Young Mice and Rats

The established role of vitamin K in nutrition is as a cofactor in the post-translational conversion of specific glutamyl to γ-carboxyglutamyl (Gla) residues in a limited number of proteins. Administration of the vitamin K antagonist warfarin has previously been shown to decrease brain sulfatide concentrations and decrease brain galactocerebroside sulfotransferase (GST) activity in young mice. A dietary deficiency of vitamin K has now been shown to decrease (P < 0.01) brain sulfatide concentrations of 30-d-old mice significantly (by 21%). Male 21-d-old rats fed an excess of vitamin K for 7 or 14 d had 26 and 31% (P < 0.05) greater GST activity and 15 and 18% (P < 0.05) greater brain sulfatide concentrations, respectively, than controls fed a vitamin K-deficient diet. Male 21-d-old rats fed a diet containing 500 mg of phylloquinone/kg diet had an intermediate response and were vitamin K sufficient by normal criteria. The vitamin K response was observed when either phylloquinone or menaquinone-4 was fed as a source of the vitamin. These data suggest that in addition to its recognized role in Gla synthesis, vitamin K status is important in the maintenance of normal complex lipid sulfatide metabolism in young rats and mice.

Lost at Sea in Search of a Diagnosis: A Case of Unexplained Bleeding.

Scurvy results from a dietary deficiency of vitamin C (ascorbic acid) and is rarely thought of in modern day medicine. It now almost always occurs in pediatric patients with behavioral diagnoses, nutritionally restricted diets, and food allergies. Symptoms of scurvy include ecchymoses, bleeding gums, and arthralgias. Here, we present a 17-year-old male with autism spectrum disorder and a diet severely deficient in ascorbic acid due to textural aversion and food preferences. He presented with recurrent arthritis, hemarthrosis, bruising, and anemia. His vitamin C level was low, and his symptoms improved promptly after treatment with ascorbic acid.

Awareness of childhood blindness in parents attending Paediatrics Ophthalmology outpatient department

Background: Blindness is defined by World Health Organisation as having a visual acuity of <3/60 in the better eye. Thirty-seven million people are blind worldwide. One million and four hundred thousand are children. The causes of blindness in children vary according to region and socioeconomic development. The aim of our study is to identify a range of potential issues relating to parental awareness and perceptions of common eye diseases affecting children. Materials and Methods: The type of study was population-based, prospective, cross-sectional study conducted on parents of 200 children ranging from 0 to 16 years of age, attending Paediatric Ophthalmology clinic during the month of August and September 2014. This was an open-ended questionnaire-based study and only the participants who consented were enrolled in the study. Results: The most common eye problem detected among 200 of children was refractive errors. The incidence of refractive errors was found to be 103 out of 200 (51.5%). This is followed by 71 (35.5%) cases of squint/strabismus. Of 200 parents, 150 (75%) think the present eye condition of their child will reduce the eyesight. However, they did not know about the nature of the eye problem. Forty-four (22%) parents did not know anything about the eye condition of their child. Seventy (35%) parents were apprehensive about the use of spectacles in the children suffering from refractive errors. One hundred and six (53%) parents came to know about the eye problem of their child from the teacher of the child and 63 (31.5%) parents got information from their family doctor. Conclusions: As the number of mothers attending the eye department with the child is high, so there is more need of educating the mothers about the eye conditions of the child. Education and socioeconomic conditions affect the knowledge and awareness level of the parents regarding eye problems. Most of the children attending outpatient department were found to be in the age group of 5-8 years. This may point toward factors like dietary deficiency of Vitamin A and other important nutrients. Commonest eye problem was of refractive errors among children.

Scurvy in pediatric age group - A disease often forgotten?

Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated.

Spatial periodicity in growth plate shear mechanical properties is disrupted by vitamin D deficiency

The growth plate is a highly organized section of cartilage in the long bones of growing children that is susceptible to mechanical failure as well as structural and functional disruption caused by a dietary deficiency of vitamin D. The shear mechanical properties of the proximal tibial growth plate of rats raised either on normal or vitamin D and calcium deficient diets were measured. A sinusoidal oscillating shear load was applied to small excised growth plate specimens perpendicular to the direction of growth while imaging the deformation in real time with a fast confocal microscope. Local deformations and shear strains were quantified using image correlation. The proliferative zone of the growth plate bores the majority of the shear strain and the resting, hypertrophic and calcification zones deformed less. Surprisingly, we regularly observed discontinuous deformations in the proliferative zone in both groups that resembled cell columns sliding past one another in the direction of growth. These discontinuities manifested as regions of concentrated longitudinal shear strain. Furthermore, these shear strain concentrations were spaced evenly in the proliferative zone and the spacing between them was similar across growth plate regions and across control specimens. In contrast to the healthy controls, the vitamin D deficient growth plate exhibited larger variations in the size and orientation of cellular columns in the proliferative and hypertrophic zones. High strains were observed between columns, much as they were in the controls. However, the regular spacing of shear strain concentrations was not preserved, echoing the observation of decreased structural organization.

Nutritional Status of Orange-Fleshed Sweet Potatoes in Alleviating Vitamin A Malnutrition through a Food-Based Approach

Sweet potato (Ipomoea batatas L. Lam), the second most important root tuber and the seventh most important food crop of the world, although categorized as “poor man’s food” or “famine crop”, has tremendous potential to contribute to a food based approach to promote food security, to alleviate poverty and to supplement as an alternative staple food for the resource poor farmers, because of its diverse range of positive attributes like high yield with limited inputs, short duration, high nutritional value and tolerance to various production stresses. Orange-fleshed sweet potato is now emerging as an important member of the tropical tuber crops having great possibility for being adopted as regular diet of the consumer food chain to tackle the problem of vitamin A deficiency. Apart from cheap source of energy, the tubers are rich in starch, sugars, minerals and vitamin A in the form of β-carotene. Thus, the poor people having only limited access to the expensive vitamin A rich animal foods like fish oil, egg, milk and butter, can meet the daily requirement of vitamin A along with some other essential nutrients through increased consumption of these tubers. Being rich in β-carotene, a precursor of vitamin A, orange-fleshed sweet potatoes are now considered as an important biofortified crop in many developing countries in alleviating Vitamin A malnutrition. The focus of this paper is on identification of potential cultivars of orange-fleshed sweet potato having high β-carotene and higher percentage of its retention after cooking. The cultivars with high β-carotene had consistently orange flesh and those with low to very low in β-carotene content had light orange or yellow-fleshed tubers. Results of this study suggest that increased consumption of orange-fleshed sweet potato in either fresh or cooked form can contribute considerably in alleviating dietary deficiency of Vitamin A and thereby combating night blindness, a major public health concern in rural areas.

Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice

Vitamin A is a common lipophilic vitamin, and its function is mainly mediated by the binding of its metabolite retinoic acid to retinoic acid receptors (RARs) and retinoid X receptors. Recently, it was reported that the expression of the RARb (an RAR subtype) gene determines the contribution of the delta oscillation in the sleep electroencephalogram (EEG) patterns in mice. We also reported that 4-week dietary deficiency of vitamin A (VAD) causes the attenuation of delta power in sleep and spontaneous activity in mice. However, our previous study could not clarify whether the attenuation of delta power by VAD is attributed to the suppression of RARs. To address this problem, we investigated whether the chronic administration of LE540 (30 mg/kg/day), an antagonist of RARs, for 1 or 4 weeks attenuated EEG delta power during sleep in mice. Consequently, 4-week LE540 administration induced a significant attenuation of wakefulness and delta power in non-rapid eye movement sleep. Western blot analysis revealed a significant decrease in the expression of dopamine D1 receptor (D1DR) in the striatum and tyrosine hydroxylase in the midbrain of mice that were administered LE540 for 4 weeks. High-performance liquid chromatography analysis of striatal tissue revealed a significant decrease in the homovanillic acid/dopamine ratio. Meanwhile, dopamine levels did not change in these mice. Our results suggest that the 4-week antagonism of RARs induces the attenuation of delta power. However, the attenuation of delta power may be elicited indirectly by the decrease of wakefulness followed by the hypo-expression of dopamine receptors especially D1DR.

EFFECTS OF DIFFERENT DIETARY VITAMIN C LEVELS ON CHINESE LONGSNOUT CATFISH (&lt;I&gt;LEIOCASSIS LONGIROSTRIS GUNTHER&lt;/I&gt;)

Vitamin C is ail essential micro-nutrient for most fish and plays an important role in immunity and physiology. The deficiency of dietary vitamin C can result in the damage on fish. The study on the deficiency symptom and the sensitive indicator of vitamin C could provide useful information for fish feed industry. This experiment was conducted to investigate the effects of dietary Vitamin C levels oil growth performance, immune and physiological responses in Chinese long-snout catfish (Leiocassis longirostris Gunther), which is ail high value aquaculture fish in China. Three practical diets containing 38, 364 and 630mg/kg vitamin C were fed to Chinese longsnout catfish (23.19 +/- 0.58g) for 8 months. Vitamin C was used in the form of L-ascorbyl-2-polyphosphate. The results indicated that the Chinese longsnout catfish in 38mg/kg vitamin C groups showed typical vitamin C deficiency symptom : skin color turning darker, spinal deformities and scoliosis, erosion of fins, anaemia. SGR and the serum lysozyme activities decreased significantly (p 0.05). The inductive HSP70 in liver was not detected by western-blotting in all groups. In conclusion, serum cortisol and hepatic HSP70 were not the sensitive indicators for vitamin C deficiency symptom, but the serum lysozyme, hepatic SOD activity, hepatic MDA content and the haematological index ( red blood cell number and hemoglobin content) were the more reliable makers to indicate the physiological status in Chinese longsnout catfish.

Dietary Vitamin E and Quercetin Modulate Inflammatory Responses of Collagen-Induced Arthritis in Mice

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints. This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. Male DBA/1J mice were maintained on either a control diet (C) or a vitamin E-depleted (-VE) diet for 4 weeks before arthritis induction. The mice in the control group were subdivided into the control group (C/C), the 0.05% alpha-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). The vitamin E-depleted group was subdivided into the -VE group (-VE/-VE), the 0.05% alpha-tocopherol-supplemented group (-VE/+VE), and the 0.5% quercetin-supplemented group (-VE/+Q) (in total, six groups, 27 mice per group). The mice were maintained on the experimental diets for 9 weeks. Study results indicate that the -VE/-VE group showed higher joint tissue tumor necrosis factor-alpha and interleukin-1beta mRNA expressions, whereas alpha-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group. The mice fed the -VE/-VE diet exhibited higher levels of circulating macrophage chemoattractant protein 1, nitric oxide, and prostaglandin E(2) compared to those in other groups. Supplementation with alpha-tocopherol or quercetin in mice fed -VE diet decreased these markers similar to those of the mice in the C/C group. No supplementation effect was observed, however, in the mice fed with the control diet prior to RA induction. These results suggest that dietary deficiency of vitamin E increases inflammatory responses and that antioxidants successfully suppress the inflammatory responses. However, significant clinical improvement may require longer observation.

Osteoskeletal Manifestation of Scurvy in a Male Infant (Case Report)

Scurvy, a disease of dietary deficiency of vitamin C, was uncommon in the last century due to improved nutrition and health care. However, in the last decade it was increasingly reported in adult population. In a period of infancy, scurvy appears after the age of five months and is related mainly to malnutrition. The main symptoms are vascular purpura, bleeding and gum abnormalities, but musculoskeletal manifestations could also be prominent. Children experience severe lower limb pain related to subperiosteal bleeding. The misdiagnosis with rickets and arthritis is common. We present a case of scurvy in 8 month boy with osteoskeletal manifestation, very rare seen in contemporary European pediatrics. The diagnosis of our patient is made by clinical presentation (such as haematuria, edema of lower extremities as well as swollen right leg), some biochemical parameters and radiological finding. The therapeutically outcome and follow-up of the boy confirmed the diagnosis and etiology.

Homocysteine, vitamins, and vascular disease prevention

In mid-20th century United States, deaths from vascular disease reached a peak incidence in 1955, but little was known about the underlying causes of this epidemic of disease. The significance of homocysteine in human disease was unknown until 1962, when cases of homocystinuria were first associated with vascular disease. Analysis of an archival case of homocystinuria from 1933 and a case of cobalamin C disease from 1968 led to the conclusion that homocysteine causes vascular disease by a direct effect of the amino acid on arterial cells and tissues. The homocysteine theory of arteriosclerosis attributes one of the underlying causes of vascular disease to elevation of blood homocysteine concentrations as the result of dietary, genetic, metabolic, hormonal, or toxic factors. Dietary deficiency of vitamin B-6 and folic acid and absorptive deficiency of vitamin B-12, which result from traditional food processing or abnormal absorption of B vitamins, are important factors in causing elevations in blood homocysteine. Numerous clinical and epidemiologic studies have established elevated blood homocysteine as a potent independent risk factor for vascular disease in the general population. Dietary improvement, providing abundant vitamin B-6, folic acid, and cobalamin, may prevent vascular disease by lowering blood homocysteine. The dramatic decline in cardiovascular mortality in the United States since 1950 may possibly be attributable in part to voluntary fortification of the food supply with vitamin B-6 and folic acid. Fortification of the US food supply with folic acid in 1998, as mandated by the US Food and Drug Administration, was associated with a further decline in mortality from vascular disease, presumably because of increased blood folate and decreased blood homocysteine in the population.

Is vitamin C an effective antihypertensive supplement? A review and analysis of the literature

Objective Hypertension is a common condition with high mortality from associated diseases. Epidemiological evidence suggests that a dietary deficiency of vitamin C may be a risk factor for hypertension. However the literature on vitamin C interventional trials appears divided on the efficacy of vitamin C utilization clinically. Methods A literature search and review of published trials using vitamin C in treating patients with hypertension was undertaken. Relevant references were located using MEDLINE (1966–2005) and the bibliographies of located articles. Results Thirteen trials making up 14 separate groups were identified and analyzed providing a pooled population of 284 hypertensive patients (52% female), with a weighted mean age of 58.8 ± 9.5 years. Median vitamin C dose and study intervention duration was 500mg/day and 6 weeks respectively. The weighted mean baseline and post treatment systolic blood pressures across all 14 groups were 149.6 ± 11.1 and 145.7 ± 11.0 mmHg respectively. This represented a systolic blood pressure decrease of 3.9 mmHg. Seven of the 14 groups ascertained statistically significant reductions (p < .05) in systolic blood pressures. However only 2 of the 14 groups found significant reductions in diastolic blood pressure. The weighted mean baseline and post treatment diastolic blood pressures across all 14 groups were 84.6 ± 4.4 and 82.5 ± 4.1 mmHg respectively. This represented a diastolic blood pressure decrease of 2.1 mmHg. Conclusion Vitamin C supplementation in hypertensive patients appears to possess modest effects on reducing systolic blood and diastolic blood pressure.

Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron

To determine whether equine motor neuron disease (EMND) could be induced in adult horses fed a diet low in vitamin E and high in copper and iron. 59 healthy adult horses. Horses in the experimental group (n = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high in iron and copper in addition to free-choice grass hay that had been stored for 1 year. Control horses (n = 51) were fed a concentrate containing National Research Council-recommended amounts of copper, iron, and vitamin E. The hay fed to control horses was the same as that fed to experimental horses, but it had not been subjected to prolonged storage. Control horses had seasonal access to pasture, whereas experimental horses had no access to pasture. Horses that developed clinical signs of EMND were euthanatized along with an age-matched control horse to determine differences in hepatic concentrations of vitamin E, vitamin A, copper, iron, and selenium. 4 experimental horses developed clinical signs of EMND. Plasma concentrations of vitamin E decreased in all 8 experimental horses. There were no significant changes in plasma concentrations of vitamin A, selenium, and copper or serum concentrations of ferritin. There were no significant differences in those analytes between experimental horses with EMND and experimental horses that did not develop EMND. No control horses developed EMND. Results suggest that lack of access to pasture, dietary deficiency of vitamin E, or excessive dietary copper are likely risk factors for EMND.

Vitamin E prevents cell death induced by mild oxidative stress in chicken skeletal muscle cells

Apoptosis and necrosis are two forms of cell death that can occur in response to various agents and oxidative damage. In addition to necrosis, apoptosis contributes to muscle fiber loss in various muscular dystrophies as well participates in the exudative diathesis in chicken, pathology caused by dietary deficiency of vitamin E and selenium, which affects muscle tissue. We have used chicken skeletal muscle cells and bovine fibroblasts to study molecular events involved in the cell death induced by oxidative stress and apoptotic agents. The effect of vitamin E on cell death induced by oxidants was also investigated. Treatment of cells with anti-Fas antibody (50 to 400 ng/mL), staurosporine (0.1 to 100 μM) and TNF-α (10 and 50 ng/mL) resulted in a little loss of Trypan blue exclusion ability. Those stimuli conducted cells to apoptosis detected by an enhancement in caspase activity upon fluorogenic substrates but this activity was not fully blocked by the caspase inhibitor Z-VAD-fmk. Oxidative stress induced by menadione (10, 100 and 250 μM) promoted a significant reduction in cell viability (10%, 20% and 35% for fibroblasts; 20%, 30% and 75% for muscle cells, respectively) and caused an increase in caspase activity and DNA fragmentation. H 2O 2 also promoted apoptosis verified by caspase activation and DNA fragmentation, but in higher doses induced necrosis. Vitamin E protected cells from death induced by low doses of oxidants. Although it was ineffective in reducing caspase activity in fibroblasts, this vitamin diminished the enzyme activity in muscle cells. These data suggested that oxidative stress could activate apoptotic mechanisms; however the mode of cell death will depend on the intensity and duration of the stimulus, and on the antioxidant status of the cells.

Scurvy: How a surgeon, a mariner, and a gentleman solved the greatest medical mystery of the age of sail

Scurvy: How a surgeon, a mariner, and a gentleman solved the greatest medical mystery of the age of sail

Vitamin A deficiency reduces liver and colon docosahexaenoic acid levels in rats fed high linoleic and low alpha-linolenic acid diet

Studies indicate that the transcription factor peroxisome proliferator-activated receptors (PPARs) regulate the activity of delta-6 and -5 desaturases and several key enzymes of peroxisomal β-oxidation, including acyl-CoA oxidase. These enzymes are vital for the synthesis of docosahexaenoic (22:6ω3; DHA) and osbond (22:5ω6, OA) acids. An activated PPAR must form a hetrodimer with the obligate cofactor retinoid X receptor (RXR) to interact with a peroxisome proliferator responsive element (PPRE) of a target gene and to regulate transcriptional expression. The vitamin A metabolite, 9- cis retinoic acid, is the most potent ligand of RXR. We have tested the possibility that deficiency of vitamin A would compromise tissue levels of both DHA and OA in rats. Two groups of male Wistar rats were randomly distributed to receive vitamin A deficient (VAD) or sufficient (VAS) diet. After seven weeks of feeding, the rats were killed and colon and liver tissues removed for the analysis of fatty acids and antioxidant status. The VAD compared to the VAS rats had elevated levels of arachidonic (AA, P<0.001), adrenic acid (22:4ω6, P<0.005) and OA ( P<0.0001) and reduced proportions of eicosapentaenoic (EPA, docosapentaenoic (DPA), DHA and total ω3 fatty ( P<0.0001) in colon choline phosphoglycerides (CPG). Similarly, liver CPG of the VAD rats had higher AA and adrenic acid and OA ( P<0.0001), and lower EPA, DPA and DHA ( P<0.0001) than the VAS rats. There was a similar fatty acid pattern in ethanolamine phosphoglycerides of the colon and liver tissues. These differences could not be explained by the conventional microsomal-peroxisomal pathway of the synthesis of the long-chain ω6 and ω3 polyunsaturated fatty acids. We postulate that deficiency of dietary vitamin A and the consequential depletion of retinoids inhibits DHA, and enhances OA, synthesis by differential effects on the independent synthetic pathways of the two fatty acids in the mitochondria. Various studies have documented that both DHA and vitamin A are vital for optimal visual and neural development and function. There is a need for further investigations to elucidate how vitamin A deficiency reduces membrane DHA level, and to delineate the synergistic effect of the two nutrients on vision, learning and memory.

A conserved role for retinoid signaling in vertebrate pancreas development.

Retinoic acid (RA) signaling plays critical roles in the regionalization of the central nervous system and mesoderm of all vertebrates that have been examined. However, to date, a role for RA in pancreas and liver development has only been demonstrated for the teleost zebrafish. Here, we demonstrate that RA signaling is required for development of the pancreas but not the liver in the amphibian Xenopus laevis and the avian quail. We disrupted RA signaling in Xenopus tadpoles, using both a pharmacological and a dominant-negative strategy. RA-deficient quail embryos were obtained from hens with a dietary deficiency in vitamin A. In both species we found that pancreas development was dependent on RA signaling. Furthermore, treatment of Xenopus tadpoles with exogenous RA led to an expansion of the pancreatic field. By contrast, liver development was not perturbed by manipulation of RA signaling. Taken together with our previous finding that RA signaling is necessary and sufficient for zebrafish pancreas development, these data support the hypothesis that a critical role for RA signaling in pancreas development is a conserved feature of the vertebrates.

Retinoic acid regulates endothelial cell proliferation during vasculogenesis.

A dietary deficiency of vitamin A is associated with cardiovascular abnormalities in avian and murine systems. Retinoic acid (RA) is the active metabolite of vitamin A and whether it directly regulates mammalian blood vessel formation has not been determined and is investigated herein. We used mice rendered RA-deficient via targeted deletion of retinaldehyde dehydrogenase 2 (Raldh2(-/-)), the enzyme required to produce active RA in the embryo. Histological examination at E8.0-8.5, prior to cardiac function and systemic blood circulation, revealed that capillary plexi formed in Raldh2(-/-) yolk sacs and embryos, but were dilated, and not appropriately remodeled or patterned. Raldh2(-/-) endothelial cells exhibited significantly increased expression of phosphohistone 3 and decreased expression of p21 and p27, suggesting that RA is required to control endothelial cell cycle progression during early vascular development. Uncontrolled endothelial cell growth, in Raldh2(-/-) mutants, was associated with decreased endothelial cell maturation, disrupted vascular plexus remodeling and lack of later stages of vessel assembly, including mural cell differentiation. Maternally administrated RA restored endothelial cell cycle control and vascular patterning. Thus, these data indicate that RA plays a crucial role in mammalian vascular development; it is required to control endothelial cell proliferation and vascular remodeling during vasculogenesis.

Infantile scurvy: a historical perspective.

Scurvy, a disease of dietary deficiency of vitamin C, is uncommon today. Among diseases, scurvy has a rich history and an ancient past. The Renaissance (14th to 16th centuries) witnessed several epidemics of scurvy among sea voyagers. In 1747, James Lind, a British Naval surgeon, performed a carefully designed clinical trial and concluded that oranges and lemons had the most antiscorbutic effect. Eventually, with the provision of lemon juice to the sea voyagers, scurvy became rare at sea. Infantile scurvy appeared almost as a new disease toward the end of the 19th century. The increased incidence of infantile scurvy during that period was attributed to the usage of heated milk and proprietary foods. Thomas Barlow described the classic clinical and pathologic features of infantile scurvy in 1883. Between 1907 and 1912, Holst and Frolich induced and cured scurvy in guinea pigs by dietary modification. In 1914, Alfred Hess established that pasteurization reduced the antiscorbutic value of milk and recommended supplementation of fresh fruit and vegetable juices to prevent scurvy. Such pioneering efforts led to the eradication of infantile scurvy in the United States. A brief history of infantile scurvy is provided.

Genetic causes of rickets.

Dietary deficiency of vitamin D, genetic disorders of its bioactivation to 1,25-dihydroxyvitamin D [1,25(OH)2D], or disorders of vitamin D action can cause rickets. The rate-limiting, hormonally-regulated, biologically activating step in the synthesis of 1,25(OH)2D is the 1 alpha-hydroxylation of 25-hydroxyvitamin D, which occurs in kidney and other tissues and is mediated by a mitochondrial cytochrome P450 enzyme, P450c1 alpha. After many years of effort, the cDNA and gene for this enzyme were cloned in late 1997. Mutations in the P450c1 alpha gene, located on chromosome 12, cause 1 alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type I, an autosomal recessive disease characterized by rickets and impaired growth due to failure of renal synthesis of 1,25(OH)2D. X-linked hypophosphatemic rickets, a dominantly inherited disease, is caused by mutations in the PHEX gene, whose function in regulating renal phosphate and vitamin D metabolism remains to be elucidated.