Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We treated two infants with failure to thrive who presented with clinical evidence of conjunctival and corneal xerosis. One patient was referred with possible infectious corneal ulcer thought to exist because there were deep peripheral ulcerations of the cornea and associated hypopyon. The other patient was initially thought to have a nasolacrimal duct obstruction because of excessive tearing. Xerophthalmia secondary to vitamin A deficiency was suspected and led to the diagnosis and treatment of cystic fibrosis in each case. Therapy with vitamin A promptly resolved the xerosis, but it also caused a transient rise in intracerebral pressure. Xerophthalmia can still be a problem in developed countries when underlying disorders, such as cystic fibrosis, lead to vitamin A malabsorption.
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PMID:Xerophthalmia and cystic fibrosis. 231 Mar 33

Wilson's disease is a rare genetic disease involving the malabsorption of copper by the body. The most common characteristic sign is the presence of Kayser-Fleischner ring surrounding the cornea. Other systemic and motor signs have been documented as well as MRI changes within the brain and brainstem. This rare case illustrates the potential importance of audiometric assessment for patients with Wilson's disease who complain of hearing loss, tinnitus and intra-aural pressure. Unilateral findings were significant for retrocochlear neural transmission delays.
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PMID:Rare auditory-electophysiology finding in Wilson's disease. 1578 78

The term "nutritargeting" in analogy to the term "drug targeting" means targeting nutrients to specific "target" tissues. What is the rationale for this idea? Some tissues obviously are able to accumulate micronutrients selectively and to use them predominantly for specific functions. It has, for instance, been known for a long time that the accumulation of beta-carotene in the skin does not only provide a "golden-yellow" color but considerable antioxidative protection as well. Yet beta-carotene is only one of many antioxidants, which can be detected in the skin. Other carotenoids, for example, lutein and zeaxanthine, are preferentially found in the macula lutea, the so-called yellow spot in the eye. Here, carotenoids are subject to a metabolism typical for that tissue, which cannot be found in other tissues (e.g., formation of meso-zeaxanthine). In addition, they can specifically be absorbed into the macula. In the macula, they protect the retinal pigment epithelial cells against oxidative damage from UV light. Indeed, these two carotenoids can be protective against age-dependent macula degeneration. Another example is the tissues that are particularly rich in vitamin C, for example, the cortex of the suprarenal gland or the lens: here, vitamin C fulfills both antioxidative functions and metabolic ones as it helps in the formation of collagen structures. Approximately 40% of the body's ascorbate is stored in skeletal muscle because this tissue is relatively abundant and its cellular concentration is tenfold higher than the plasma level. Similarly, the intracellular ascorbate concentration in the brain (3 mM) greatly exceeds the level in the extracellular fluid (200-400 muM). The majority of ascorbate is stored in the astroglial cells that are capable of reducing great quantities of DHAA to ascorbate, which then becomes available for release back into the extracellular fluid. Thus, the accumulation of vitamins respectively micronutrients in single tissues is not limited to a pure storage process like the storage of vitamin A in the liver, but is often connected with important and tissue-specific metabolic functions. When single micronutrients are applied for prevention or even intervention in diseases of organs or tissues, they are usually administered in higher doses for a longer period of time. The hope is to accumulate it this way sufficiently in the tissue and to thus be able to ensure the therapeutic success. This procedure, however, leads to a "flooding" of the whole organism with micronutrients and their potential enrichment in tissues which would usually not accumulate the respective micronutrient. Thus, unexpected side effects may occur. An attractive solution to these problems in the future could be to wrap up or apply micronutrients in such a way that they can selectively reach the targeted tissue. For this approach, called "drug targeting" by pharmacologists, one could introduce the analogous expression "nutritargeting" with respect to micronutrients. For such a nutritargeting there are already a lot of examples and developments which show that it is possible to accumulate micronutrients in target tissues while simultaneously circumventing or protecting other tissues. A substantial requirement for the development of "carriers" for nutritargeting is the availability of procedures or specific carriers, which allow the selected nutrients to bypass the main barriers that are encountered when, for example, circumventing the enteral route in the targeting process. The entrance areas for such a targeting are the nasal mucosa, the oral mucosa, the cornea, the skin, or the lung. In the case of enteral application of proteins, the packaging has to resist gastric digestion and the body must be able to absorb the particles through the intestinal mucosa without hydrolyzing the proteins in order for them to reach the systemic circulation. Another field in which nutritargeting may play an important role is the diseases where either systemic absorption is not possible (e.g., malabsorption/maldigestion) or where local deficits occur, which may not or only inadequately be supplied by systemic application.
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PMID:Nutritargeting. 1829 7

Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the first manifestations of the disease can be psychiatric which, according to the literature, accounts for only 10% of the cases. The disease can be revealed by isolated behavioral problems, an irrational syndrome, a schizophrenic syndrome, or a manic-depressive syndrome. Damage to the central nervous system can be more severe, thus, several differential diagnoses have been discussed: a psychotic disorder of late appearance; a depressive state; a mental confusion disorder. The clinical syndrome is complex. Indeed, it is the polymorphism, which dominates in the description of the psychiatric demonstrations of the disease. This can lead to prejudicial diagnostic wandering, particularly since heavy sedative treatment may be required to suppress behavioral problems. Clinically, Wilson's disease generally appears between the age of 10 and 20. It rarely remains masked until after the age of 40. The first manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). The inaugural disorder can finally take on a haematological, renal, or mixed form in approximately 15% of the cases. We have detailed the principal clinical elements. In approximately 40-50% of the patients, the first manifestation of the disease affects the central nervous system, where it can cause either a progressive neurological disease, or psychiatric disorders. The ophthalmologic disorder is dominated by Kayser-Fleischer's ring, representing a green or bronze colored ring on the periphery of the cornea. It occupies the higher pole of the cornea, then the lower pole, and extends to the whole circumference. It is generally only visible under examination with a slit lamp. It disappears on average within 3-5 years following copper chelating therapy. Kayser-Fleischer's ring has been described other than in Wilson's disease, in exceptional cases of prolonged cholestasis. On haematological level, the hyperhaemolysis is due to the toxicity of the ionic copper, released massively in the plasma by hepatocellular necrosis. The other manifestations can be found in the following organs: renal, osteoarticular, cardiac, endocrine, cutaneous, and in the teguments. Until 1952, the diagnosis was evoked only on clinical symptomatology. It can henceforth be marked unambiguous, even in the absence of any symptom, by the description of a ceruloplasmin plasma concentration of less than 200 ml/l, and of a Kayser-Fleischer's ring. Hepatic copper on sample is constantly increased during the disease (from 3 to 25 micromol/g of dry weight). On the other hand, the absence of a reduction in the plasma ceruloplasmin does not make it possible to exclude the diagnosis. Conversely, a reduction in ceruloplasmin can exist other than in Wilson's disease (nephritic syndrome, malabsorption syndrome, or severe hepatic insufficiency). Kayser-Fleischer's ring is quasiconstant among patients with neuropsychiatric demonstrations (thus, its absence represents a very strong argument against the diagnosis). It can on the other hand be lacking during hepatic forms, and in this case, its absence is not an argument against the diagnosis. Magnetic resonance imaging can reveal abnormal signals of the grey cores. A genetic study is conducted by liaison analysis in the event of a family history of the disease. When it is not treated, Wilson's disease induces lesions of the tissues, the outcome of which is always fatal. Treatment relies on the regulation of copper chelation, which improves the prognosis, and zinc, which captures the copper in a nontoxic form. The severe psychiatric disorders observed during Wilson's disease may require tranquilizers, but care should be taken because of potential neurological or hepatic side effects. Lithium seems an interesting treatment and remains theoretically indicated, taking into account the scarcity of the extrapyramidal symptoms and the hepatic dysfunction among patients at the stage of cirrhosis, since it is not metabolized in the liver. Although rare, it is important to approach Wilson's disease in psychiatry because the psychiatric manifestations can precede the somatic disorders and help to pose the diagnosis. We stress the importance of the early diagnosis of the pathology, the outcome of which is fatal in the absence of specific treatment.
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PMID:[The onset of psychiatric disorders and Wilson's disease]. 1878 84