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)

Patients with phenylalanine hydroxylase deficiency show increased concentrations of biopterins and neopterins, and reduced concentrations of serotonin and catecholamines, when phenylalanine concentrations are raised. The pterin rise reflects increased synthesis of dihydroneopterin and tetrahydrobiopterin, and the amine fall a reduction in amine synthesis due to inhibition by phenylalanine of tyrosine and tryptophan transport into neurones. The pterin and amine changes appear to be independent of each other and are present in the central nervous system as well as the periphery; they disappear when phenylalanine concentrations are reduced to normal. Patients with arginase deficiency show a similar amine disturbance but have normal pterin levels. The amine changes probably contribute neurological symptoms but pterin disturbance is not known to affect brain function. Patients with defective biopterin metabolism exhibit severely impaired amine synthesis due to tetrahydrobiopterin deficiency. Pterin concentrations vary with the site of the defect. Symptoms include profound hypokinesis and other features of basal ganglia disease. Neither symptoms nor amine changes are relieved by controlling phenylalanine concentrations. Patients with dihydropteridine reductase (DHPR) deficiency accumulate dihydrobiopterins and develop secondary folate deficiency which resembles that occurring in patients with defective 5,10-methylene tetrahydrofolate reductase activity. The latter disorder is also associated with Parkinsonism and defective amine and pterin turnover in the central nervous system, and a demyelinating illness occurs in both disorders. In DHPR deficiency cerebral calcification may develop in a similar distribution to that seen in congenital folate malabsorption and methotrexate toxicity. Symptoms are ameliorated by therapy with 5-formyltetrahydrofolate but exacerbated by folic acid.
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PMID:Pteridines and mono-amines: relevance to neurological damage. 354 Sep 26

A severely affected case of Hartnup disease is reported, where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, beta-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal.
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PMID:Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease. 424 31

Twenty-four senile dementia patients in the age range 65-85 years were subjected to a new sensitive tryptophan loading test: Dopa-Tryptophan loading ("Dop-Try loading") in order to determine whether Try malabsorption occurs in senile dementia and if so how frequent this is. For comparison the same loading test was performed on 23 subjects in the same age grouping but with normal metal function. The differences in Try absorption were statistically analyzed and this revealed that absorption was less effective in the senile dementia group. Four patients with Try malabsorption were treated with 3 G 1-Try + 50 Mg dl-5-hydroxytryptophan (5-HTP) per day orally for 20-30 days and four patients with normal absorption were treated in the same way. The Dop-Try loading test was repeated after this treatment. Two patients showed improved absorption and coincident mental improvement, while one showed decreased absorption and mental deterioration. One died during the course of the treatment. None of the four patients with normal absorption showed mental improvement after the treatment. This pilot study suggests that increase in Try absorption following the Try treatment is a necessary condition for improvement in the mental state. The study is being continued with larger numbers of patients.
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PMID:Tryptophan malabsorption in dementia. Improvement in certain cases after tryptophan therapy as indicated by mental behaviour and blood analysis. 617 7

Adults with intestinal malabsorption due to celiac disease show reduced central serotonin metabolism, probably induced by a lack of essential dietary factors. Investigating a role proposed for vitamin B6 deficiency, a regular finding in untreated celiacs, the present study yields no support for the hypothesis that direct inhibition at the decarboxylation step by vitamin B6 deficiency accounts for low central serotonin turnover in adult celiacs: 11 untreated patients showing reduced 5-HIAA in the cerebrospinal fluid (71+/- 26.8 pmol/ml) had a significantly higher concentration of the metabolically active B6 vitamer pyridoxal 5'-phosphate in lumbar cerebrospinal fluid (0.06 +/- 0.34 ng/ml) than controls (0.24 +/- 0.07 ng/ml) (p less than 0.01). Cerebrospinal fluid tryptophan, precursor of serotonin, was normal (2035 %/- 649 pmol/ml). Raised pyridoxal 5'-phosphate in the cerebrospinal fluid in untreated celiac disease is an unexpected finding. Possibly it is secondary to the diminished central monamine metabolism in these patients, but further studies are needed bearing in mind that mental depression is a major cause for disability in adult celiac disease.
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PMID:High level of pyridoxal 5'-phosphate in the cerebrospinal fluid of adult celiac patients. 618 88

A 14-year-old boy of Arabic origin presented with a pellagra-like rash and neurological manifestations including ataxia, dysarthria, nystagmus, and coma. There was a striking response to oral nicotinamide. The laboratory findings were not typical of Hartnup disease: aminoaciduris and indicanuria were absent and there was no evidence of tryptophan malabsorption. Tryptophan loading did not induce tryptophanuria nor did it increase excretion of xanthurenic or kynurenic acids. These findings support the possibility of a block in tryptophan degradation. The family history suggests a genetically-determined disorder.
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PMID:Familial pellagra-like skin rash with neurological manifestations. 645 Dec 1

Before dietary treatment, no significant differences, except for alanine, were found in the amino acid pattern for 22 young mothers and 33 children with protein-energy malnutrition (PEM), the characteristic feature of the serum pattern being the imbalance between essential and non essential amino acids. Apart from lysine, the essential amino acid levels were all below normal. This imbalance may be detected readily from the abnormal values of some particularly sensitive ratios: phenylalanine/tyrosine, valine/glycine, non essential amino acids/essential amino acids and, above all, serine/threonine. A striking finding was the very low threonine levels in all subjects, including local controls and the extremely low tryptophan levels in malnourished children. Before treatment, almost all the erythrocyte amino acid levels as well as the E/S ratios (erythrocytes/serum) were found to be raised in 9 children, demonstrating their poor clinical status. The urinary amino acid level was similar in both, patients before treatment and local controls. The urinary threonine level was low, like in the serum. A normalisation in most of the amino acid levels in the serum was observed upon dietary rehabilitation although not yet significant in all of them. In urine a similar tendency was observed but it was significant for threonine and methionine only, after 2 weeks treatment. Some additional urinary amino acid assays revealed changes upon two weeks dietary rehabilitation that can be interpreted as an increased production of enzymes affected by PEM as well as a growth of the patients' muscular mass. Increased free amino acid losses in the stools, caused by diarrhoea due to secondary malabsorption, and various viral and bacterial infections accompanying malnutrition, illustrate the severity of the diarrhoea.
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PMID:Biochemical study of malnutrition. Part IV. Determination of amino acids in the serum, erythrocytes, urine and stool ultrafiltrates. 678 95

Blood samples were taken from six overweight women after an overnight fast on three different occasions, before an jejunoileal bypass operation and 1 and 6 months after the operation. The preoperative levels of several plasma free amino acids were significantly elevated, e.g. leucine, isoleucine, valine, lysine, phenylalanine, tyrosine, proline and glutamic acid. One month after the operation all indispensable plasma amino acid concentrations had fallen, in particular the levels of the branched-chain amino acids (BCAA), lysine and tryptophan. Among the dispensable amino acids, plasma tyrosine, arginine and ornithine concentrations were significantly reduced. No further changes of significance were observed in samples taken 5 months later. A close correlation was observed between the plasma levels of retinol-binding protein (RBP) and thyroxine-binding prealbumin (TBPA). One month after the operation the levels of RBP and TBPA had fallen slightly in two subjects and substantially in one subject. A test diet, containing crystalline amino acids, glucose and fat emulsion was given before operation and twice after the operation. Plasma amino acid changes were studied for a period of 2 hours after the meal. The increases in plasma levels following the test meal were lower for many amino acids after the operation. A linear correlation was found between the postprandial increases in BCAA concentrations and the levels of RBP and TBPA. By using complete, carefully defined diets in loading tests, it should be possible to screen for glucose tolerance and amino acid and lipid malabsorption.
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PMID:An oral amino acid loading test before and after intestinal bypass operation for morbid obesity. 713 14

Since the first comprehensive description of the symptoms of FMS by Yunus et al (1981), numerous investigations have confirmed that FMS is a clinical entity. However, the aetiology of the syndrome is still not fully elucidated. It seems, however, logical to place the origin of the disorder in the muscle. Muscle pain, especially at the muscle-tendon junctions, fatigue and stiffness are the first symptoms. A malfunction of energy metabolism has been detected in part of the muscle fibres. However, it has to be considered that the muscle is not an isolated entity. Its activity is controlled by segmentally arranged motor units of the ventral horn of the spinal cord in response to proprioceptive afferent signals arising in the muscle spindles or in other sensory elements including nociceptors. Together with supraspinal descending inputs, the spinal motor neurone pool is the common final pathway for segmental and suprasegmental inputs, making the motor system extremely powerful for adaptive adjustments but also vulnerable if deficits occur in either of these input levels. A second, recently discovered abnormality seen in FMS is a lowered serotonin level in peripheral and most likely also central structures. The underlying mechanism seems to be defective absorption of the precursor amino acid tryptophan from the gut. Serotonin is involved centrally in the regulation of the sleep pattern, and at the spinal level it acts as a 'gain setter' of motoneurone excitability and suppresses signal transmission of noxious stimuli in dorsal horn neurones. Either of these two disturbances, muscle energy depletion or serotonin deficiency, could by itself evoke many of the symptoms of FMS, and their combined appearance will perpetuate the disease. Depressed levels of somatomedin C, caused by a deficit of stage 4 sleep-dependent release of GH, might represent an additional factor in preventing proper development or repair of myoskeletal structures. Malabsorption of certain amino acids, possibly due to a genetic disorder of gut transport mechanisms, may constitute an additional deleterious factor. The abnormalities found in the HPA and HPT axis may be seen as an attempt of the organism to restore homeostasis. The stimulus eliciting this counter-regulatory reaction may be pain or other afferent signals which normally do not reach the central nervous system. It is doubtful whether the unspecific activation of the HPA axis in a non-inflammatory disease is beneficial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress? 785 Aug 79

Goldberger discovered human pellagra was a non-infectious disease, affecting mostly the small and the timid in overcrowded institutions. Symptoms were diarrhoea, dermatitis and dementia. The staff and older children escaped the disease. They ate the meat and left the small and timid with the gravy. The 'Goldberger syndrome' is observed during competitive feeding of livestock, in ketotic animals and in the zinc depleted which are lethargic and pick all day at their feed. The pellagra preventative factor was later found to be nicotinic acid, derived from the amino acid tryptophan. Deficiencies of copper, magnesium, vitamin B6 (activated by a zinc kinase) inhibit the conversion of tryptophan to nicotinic acid. Stresses, including liver diseases, malabsorption, iron overload, porphyria, marasmus, cold stress, pregnancy, lactation, antibiotics and sulfa drugs, all increase dietary needs of nicotinic acid. Elevated free fatty acids and ketone bodies in the blood are associated with ketosis, zinc depletion and the pre-diabetic state. There is a diminished uptake of glucose by the tissues, a condition also found in parturient paresis of dairy cows when elevated hydrocortisone promotes insulin resistance and hyperglycaemia. This defect in insulin response leads to a diabetic-like state. The major predisposing factor in parturient paresis of dairy cows is hypocalcaemia. Gut absorption of dietary calcium may not meet the primary demands of lactation initiation until bone calcium mobilisation is established.
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PMID:Metabolic disorders of cattle. 839

A 47-year-old woman with seronegative polyarthritis, diarrhea, and photosensitivity dermatitis was found to have Crohn's disease and pellagra. The presence of high values of 5-hydroxyindolacetic acid in the urine began the exhaustive investigations and finally enterotomy. No mass lesion was found. Argyrophilic cells were not increased in areas of inflamed intestinal mucosa or the normal mucosa. The disagreement between biochemical and histologic findings was attributed to sampling error. Antiinflammatory treatment for Crohn's disease was given and the gastrointestinal and articular symptoms improved, excretion of 5-hydroxyindolacetic acid returned to normal and there was no relapse of pellagra. Pellagra as a complication of Crohn's disease has been described in 4 cases; malnutrition and intestinal malabsorption were the proposed mechanisms for the niacin deficiency and pellagra of those patients. In the current case, the pathogenesis of pellagra may be accounted to wastage of tryptophan by an increased pool of intestinal argyrophilic cells, suggested by increased urinary excretion of 5-hydroxyindolacetic acid.
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PMID:Crohn's disease associated with pellagra and increased excretion of 5-hydroxyindolacetic acid. 903 Jun 78


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