Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inability to synthesize vitamin C, because of a deficiency in gulonolactone oxidase (GULO) expression, is a genetic deficiency shared by a small number of animals including humans. Although the most overt symptom of vitamin C deficiency, scurvy, can be readily corrected by modest consumption of vitamin C, there is increasing interest in the effect of high-level administration in treating human disease. Using a previously derived Gulo-expressing vector, which produces murine GULO under the control of the murine cytomegalovirus (mCMV) promoter, we constructed and validated a recombinant helper-dependent adenovirus (HDAd-mCMV-Gulo) that can be used to correct this genetic defect. A human liver cell line (Hep G2) infected with the HDAd-mCMV-Gulo vector expressed GULO in a time- and gene dose-dependent manner. These cells also produced ascorbic acid when exogenous gulonolactone was supplemented in the medium. Likewise, Gulo(-/-) mice treated with HDAd-mCMV-Gulo at 2 x 10(11) VP expressed GULO in the liver and produced ascorbic acid. Serum ascorbic acid concentrations in Gulo(-/-) mice injected with GULO-expressing HDAd were elevated to levels comparable to those of wild-type mice (62 +/- 15 microM) after 4 days of infection and were maintained at significantly higher levels compared with those in untreated Gulo(-/-) mice for at least 23 days. A similar elevation was observed in urine and tissue ascorbic acid concentrations in vector-treated animals. In conclusion, we demonstrate here that gene therapeutic HDAd-mCMV-Gulo vectors can mediate the expression of GULO and endogenous production of ascorbic acid in human cells and in Gulo(-/-) transgenic mice. Taken together, these data show that a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals.
Hum Gene Ther 2008 Dec
PMID:Restoration of vitamin C synthesis in transgenic Gulo-/- mice by helper-dependent adenovirus-based expression of gulonolactone oxidase. 1876 64

We report three cases of scurvy, with differing musculoskeletal presentations, from a tertiary teaching hospital in Sydney, Australia. Case 1 was a man with cerebral palsy who presented with knee swelling following a minor injury. In Case 2, a patient with thalassaemia major presented with purpuric rash, difficulty walking and distal thigh swelling and ecchymosis. Case 3 was a man with Down's syndrome who presented with acute ankle arthritis. Scurvy in Cases 1 and 3 were related to abnormal dietary preferences, whereas in Case 2, scurvy was thought to be related to thalassaemia. All three cases responded rapidly to vitamin C replacement. The subjects did not appear malnourished as they had adequate carbohydrate and protein intake.
Int J Rheum Dis 2009 Dec
PMID:Skin, muscle and joint disease from the 17th century: scurvy. 2037 77

Approaching an uncommon disease may result in diagnostic delay even in patients with typical clinical features. In this respect, diseases related to nutritional deficiencies may represent a diagnostic challenge. We describe a 2.5-year-old child with typical features of scurvy, who was referred for autistic-like behavior and severe muscle weakness and pain in lower limbs. Extensive investigations for non-nutrition-related disorders were first performed, including a muscle biopsy showing a selective type II fibers hypotrophy. Scurvy was eventually considered, after recalling the child's peculiar dietary habits.
Neurol Sci 2011 Dec
PMID:Scurvy hidden behind neuropsychiatric symptoms. 2179 30

Scurvy is one of the oldest diseases known to mankind, caused by vitamin C deficiency. Nowadays it exists primarily in certain vulnerable populations such as patients with neurodevelopmental disabilities. Proptosis due to orbital haemorrhage is a rare complication of scurvy. Here we describe a case of diaplegic cerebral palsy presented with sudden onset of bilateral proptosis and swollen and tender knee joints. Subsequent computed tomography of the orbit revealed hematoma in the superior aspect of both orbits in the extraconal position. X-ray of the knee joints revealed bony changes consistent with scurvy. After 6 weeks of treatment with vitamin C orally, the proptosis and the bony changes returned to normal. Although scurvy is a rare disease in the general pediatric population, it still exists in certain vulnerable populations like neurologically disabled ones, and this uncommon cause for proptosis should be considered in such children.
Int Ophthalmol 2012 Dec
PMID:Bilateral proptosis in a child with vitamin C deficiency. 2275 49

Ascorbic acid is a small-molecule reductant with multiple functions in vivo. Reducing ascorbic acid intake leads to a lack of hydroxylation of prolines and lysines, causing a looser triple helix and resulting in scurvy. Ascorbic acid also acts as an antioxidant to prevent oxidative stress. Because ascorbic acid is related to disease states, rapid and convenient detection of ascorbic acid should be useful in diagnosis. Nitroxide is reduced to the corresponding hydroxylamine by ascorbic acid and a sensitive and novel approach to its detection employs covalent coupling of nitroxide with a fluorophore, leading to intramolecular quenching of fluorescence emission by electron-exchange interactions. Here, we developed a new fluorophore-nitroxide probe, Naph-DiPy nitroxide, for ascorbic acid. Naph-DiPy nitroxide rapidly reacted with ascorbic acid and showed fluorescence enhancement, but not in response to other reductants or reactive oxygen species. To confirm the practical usefulness of the fluorophore-nitroxide probe, we demonstrated the use of Naph-DiPy nitroxide for the measurement of ascorbic acid in the plasma of osteogenic disorder Shionogi rats when fed an ascorbic acid-deficient diet. The results suggest that this novel fluorophore-nitroxide probe could sensitively and easily detect ascorbic acid and be useful as a tool for the diagnosis of disease states.
Free Radic Biol Med 2012 Dec 01
PMID:Rapid and convenient detection of ascorbic acid using a fluorescent nitroxide switch. 2302 12

Nutritional deficiency syndromes, such as scurvy, pellagra, and beriberi are of historical significance but have largely disappeared from modern society. However, certain populations of children in modern society are at risk of severe nutritional complications. The rarity of these syndromes and lack of understanding about modern-day risk factors for nutritional deficiency often delays diagnosis. Dermatologists must maintain an appropriate index of suspicion for these characteristic syndromes as many of the deficiency states present with cutaneous manifestations. Here we review the cutaneous manifestations of macronutrient and micronutrient deficiency syndromes as well as those populations of children that remain at risk for developing severe disease.
Int J Dermatol 2012 Dec
PMID:Skin manifestations of nutritional deficiency disease in children: modern day contexts. 2317 Oct 6

The discovery of vitamins as essential factors in the diet was a scientific breakthrough that changed the world. Diseases such as scurvy, rickets, beriberi, and pellagra were recognized to be curable with an adequate diet. These diseases had been prevalent for thousands of years and had a dramatic impact on societies as well as on economic development. This Review highlights the key achievements in the development of industrial processes for the manufacture of eight of the 13 vitamins.
Angew Chem Int Ed Engl 2012 Dec 21
PMID:One hundred years of vitamins-a success story of the natural sciences. 2320 76

Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases. TET hydroxylases are also dioxygenases implicated in active DNA demethylation. Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C. TET1 deficiency enhances reprogramming, and its overexpression impairs reprogramming in the context of vitamin C by modulating the obligatory mesenchymal-to-epithelial transition (MET). In the absence of vitamin C, TET1 promotes somatic cell reprogramming independent of MET. Consistently, TET1 regulates 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C-dependent fashion. Our findings suggest that vitamin C has a vital role in determining the biological outcome of TET1 function at the cellular level. Given its benefit to human health, vitamin C should be investigated further for its role in epigenetic regulation.
Nat Genet 2013 Dec
PMID:Vitamin C modulates TET1 function during somatic cell reprogramming. 2427 Apr 43

It has been suggested that vitamin C deficiency/scurvy is associated with gingival inflammatory changes; however, the disorder is very infrequently encountered in the modern era. Here, we report a case of extensive gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection.
Clin Case Rep 2014 Dec
PMID:Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report. 2554 32

Scurvy was first described by Hippocrates (460-370 BC) as a condition characterised by poor dental health, bruising, bleeding and fragile skin. Despite the widespread availability of foods rich in vitamin C in Australia, scurvy continues to afflict certain high-risk subgroups of the population. Cutaneous signs may be the only manifestation of the disease, as in the case presented below, and therefore scurvy continues to be relevant to dermatologists.
Aust Fam Physician 2014 Dec
PMID:A rare cause of petechial rash in the 21st century. 2570 34


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