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)

At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction. Whatever the genetic defect might be, peroxisomal disorders should be considered in various clinical conditions, dependent on the age of onset. The prototype of peroxisomal disorders is represented by 'classical' Zellweger syndrome (ZS) which is the most severe disorder combining all the characteristic symptoms. ZS is characterized by the association of errors of morphogenesis, severe neurological dysfunction, neurosensory defects, regressive changes, hepatodigestive involvement with failure to thrive, usually early death, and absence of recognizable liver peroxisomes. Other peroxisomal disorders (pseudo-Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), pseudo-neonatal adrenoleukodystrophy, rhizomelic chondrodysplasia punctata (RCDP), and hyperpipecolic acidaemia) share some of these symptoms, but with varying organ involvement, severity of dysfunction, and duration of survival. The diagnosis should not cause difficulty when all the characteristic manifestations are present. Depending on the main presenting sign, peroxisomal disorders in neonates should be suspected in two categories of circumstances: polymalformative syndrome with craniofacial dysmorphism, and severe neurological dysfunction. During the first 6 months of life, the predominant symptoms may be hepatomegaly, prolonged jaundice, liver failure, anorexia, vomiting and diarrhoea leading to failure to thrive resembling a malabsorption syndrome; severe psychomotor retardation, hearing loss and ocular abnormalities become evident. Beyond 4 years of age, behavioural changes, intellectual deterioration, visual impairment and gait abnormalities may be the presenting symptoms. Independently of the clinical symptoms and age of onset, most peroxisomal disorders described so far can be clinically screened by recordings of electroretinogram, visual-evoked responses, and brain auditory-evoked responses, which are almost always abnormal. Nine of the 17 peroxisomal disorders with neurological involvement are associated with an accumulation of very long-chain fatty acids (VLCFA), which suggests that assay of plasma VLCFA should be used as a primary test. However, assays of plasma phytanic acid and plasma/urine bile acid intermediates should also be performed in view of the recent reports of atypical chondrodysplasia variants (without rhizomelic shortening) and isolated trihydroxycholestanoic aciduria. The differential diagnoses in various clinical conditions and age periods are discussed.
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PMID:Clinical approach to inherited peroxisomal disorders. 905 44

In primary amyloidosis the gastrointestinal tract and the liver are commonly involved, but clinical features and prognosis are mainly determined by the extent of cardiac and renal involvement. We review two cases with primary amyloidosis of the gastrointestinal tract and the liver. The predominant symptoms were malabsorption and hepatomegaly with cholestasis. The clinical aspects, diagnosis, treatment and prognosis of primary amyloidosis of the gastrointestinal tract and the liver are discussed in the context of the current literature.
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PMID:[Primary amyloidosis of the gastrointestinal tract and liver--two case reports]. 916 26

The ratio of mtDNA and a nuclear reference gene was estimated by Southern blotting in the skeletal muscle DNA of a 3-year-old girl who suffered from congenital brain damage, focal epilepsy, hepatomegaly, malabsorption syndrome and severe myopathy. The signal ratio of mtDNA versus 18S rDNA was 22% of the mean value obtained from controls. No major deletions or insertions were found and the MERRF, MELAS and NARP mutations were ruled out. Mitochondrial DNA-encoded enzyme activities and mitochondrial respiration were reduced. The analysis of the NAD(P)H and flavoprotein redox states of intact fibres revealed the presence of mitochondrial dysfunction. In tissue sections a moderate elevation of type I and type II fibre diameter variation was detected, aberrant NADH- and succinate dehydrogenase staining and some ragged red fibres. This suggested that a mitochondrial disorder caused by a decrease in the amount of intact wild-type mtDNA was responsible for the severe myopathy.
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PMID:mtDNA depletion and impairment of mitochondrial function in a case of a multisystem disorder including severe myopathy. 970 May 97

Recent studies have shown that involvement of the gastrointestinal tract is much more frequent than originally reported in patients with systemic mastocytosis. Seventy percent to 80% of patients with systemic mastocytosis are found to have gastrointestinal symptoms when a careful history is taken, and abnormalities in the gastrointestinal tract are frequently detected by endoscopic studies, functional studies of absorption, and barium studies. Because of the rarity of the disease, there are few prospective studies of gastrointestinal involvement, so the actual frequency of upper and lower gastrointestinal lesions is unknown. Furthermore, there have been no studies correlating endoscopic abnormalities of the lower gastrointestinal tract with the presence or absence of diarrhea, which is a frequent symptom (mean, 43% [range 14%-100%]). A review of gastric acid studies reveals that a proportion of patients develop gastric acid hypersecretion because of the hyperhistaminemia, which can result in ulcer disease that in turn can cause dyspeptic pain, small intestinal mucosal damage, and malabsorption. In some patients gastric acid hypersecretion in the range seen in Zollinger-Ellison syndrome can develop. A number of studies suggest that the prevalence of peptic ulcer disease has been underestimated in these patients and is certainly higher than the general population. The exact physiologic basis for the diarrhea or nondyspeptic abdominal pain remains largely unknown in these patients. Whereas some studies suggest small intestinal mucosal abnormalities are responsible for most cases of malabsorption not associated with gastric acid hypersecretion, this supposition also remains unproven. Hepatomegaly, portal hypertension, splenomegaly, and ascites occur frequently in patients with systemic mastocytosis, especially those with category II through IV disease. Whereas the histology of the liver and spleen and alterations in hepatic function studies have been well studied, the pathogenesis of each of these abnormalities has not been well studied, and almost all the information comes from a few well-studied case reports.
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PMID:Gastrointestinal abnormalities and involvement in systemic mastocytosis. 1090 42

Cystic fibrosis is believed to be rare in Arabs. We report 202 cases (114 boys and 88 girls) diagnosed in Jordan over a period of 9 years. The mean age at diagnosis was 2.9 years. Classical presentation with growth failure, malabsorption and respiratory symptoms occurred in 75.4% of cases. Eighteen (10.8%) presented with hepatomegaly, 12 (7.2%) with meconium ileus and 11 (6.6%) had Pseudo-Bartter syndrome. Thirty-eight (23%) children died, most below the age of 1 year which may reflect a more severe disease in our population. Consanguineous marriage was present in 69% of cases. Genetic screening of 84 children and 66 parents revealed 24 different CFTR mutations with a DF508 mutation accounting for only 7.4%. Among the mutations detected, six were alleles identified for the first time. The fact that boys outnumber girls might reflect more deaths in girls due to the observed gender gap in CF mortality. It is possible that the low incidence of the DF508 mutation is due to a confounding effect and the high mortality in those carrying this mutation. The large number of different mutations reflects the ethnic diversity of the Jordanian population and the complex history of the country.
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PMID:Cystic fibrosis in Arabs: a prototype from Jordan. 1121 65

We report a total of 23 novel mutations of the SLC2A2 ( GLUT2) gene in 49 patients with a clinical diagnosis of Fanconi-Bickel syndrome (FBS). Molecular genetic analysis has now been performed in more than 50% of the 109 FBS cases from 88 families that we have been able to locate world-wide since the original report in 1949. In these 49 patients, 33 different SLC2A2 mutations (9 missense, 7 nonsense, 10 frameshift, 7 splice-site) have been detected. Thus, our results confirm that mutations of SLC2A2 are the basic defect in patients with FBS. Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time. Mutations were also found in patients with atypical clinical signs such as intestinal malabsorption, failure to thrive, the absence of hepatomegaly, or renal hyperfiltration. No single prevalent SLC2A2 mutation was responsible for a significant number of cases. In a high percentage (74%) of FBS patients, the mutation is homozygous, so we conclude that the prevalence of SLC2A2 mutations is relatively low in most populations. No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected.
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PMID:The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome. 1181 Feb 92

Hereditary hemochromatosis is an inherited autosomal recessive disease, associated to a mutation in the recently described HFE gene, which is located on the short arm of chromosome 6. The product of this gene combines with the beta-2-microglobulin and the ferritin receptor, and regulates the iron absorption in the small intestine crypt cells. It is possible that the mutation may cause the increased iron uptake by the intestinal cells. The disease is very much common in men after the forties, and its expression is influenced by concomitant alcoholism, iron rich diet, oral and parenteral iron administration, menstrual blood loss or abnormal hemorrhages, blood donations, pregnancy, lactation, and iron malabsorption clinical conditions, like celiac disease. Many patients are asymptomatic, and the diagnosis may be suspected by hepatomegaly of unknown cause, abnormal iron metabolism tests, increased serum aminotransferase levels, diabetes mellitus, and anonymous arthropathy. Less commonly hereditary hemochromatosis presented by symptoms and signs of chronic liver disease, or by the classic triad described by Trousseau skin pigmentation, hepatomegaly and diabetes mellitus. The diagnosis is confirmed by the increased serum ferritin levels and transferrin saturation, and the stainable iron in hepatocytes, measured by scale devised by Scheuer et al, or the measurement of the hepatic iron. The C282Y mutation was found in 64 to 100% of patients; eventually, subjects with hepatic iron overload identical to hereditary hemochromatosis has no mutation, and homozygous for the C282Y mutation do not express iron overload. Iron is best and quickly removed by weekly or twice-weekly phlebotomy of 500 ml, containing approximately 250 mg iron. One to 3 years of weekly phlebotomy may be required to reduce stores to normal. As a guide to long-term maintenance therapy, is recommended phlebotomy every 3 months and the serum ferritin level should be maintained by less than 50 ng/ml.
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PMID:[Hereditary hemochromatosis]. 1217 Feb 86

A 17-year-old boy had a 3-year history of diabetes mellitus, malabsorption syndrome, and skin changes consisting of induration, hyperpigmentation, and hypertrichosis on the anterior aspect of both thighs, lower abdomen, and scrotum. Physical examination found hypogonadism, hepatomegaly, gynecomastia, growth retardation, and ankle edema. There was no neuropathy or plasma cell dyscrasia. However, the characteristic skin changes and the combination of symptoms suggest polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes syndrome. This is a rare multisystemic disorder of obscure pathogenesis and no conspicuous heredity. Overproduction of vascular endothelial growth factor is thought to cause microangiopathy, neovascularization, and accelerated vasopermeability causing the multiorgan deterioration. Cyclophosphamid cytostatic therapy seems beneficial.
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PMID:POEMS in childhood. 1665 Feb 24

Given the complex immune function of the gastrointestinal (GI) tract, it is not surprising that many children with primary immunodeficiencies present with GI tract manifestations. Although many immunodeficiency disorders present with overt evidence of immune dysregulation, a few can present in older children with more subtle signs and symptoms. Such children may present first to a gastroenterologist with common symptoms, including malabsorption, diarrhea, hepatomegaly, or inflammatory bowel disease, which may actually be a manifestation of their underlying immune disorder. A thorough clinical history in combination with a careful review of histology from biopsies may reveal clues that one is dealing with a disease entity outside the norm and may prompt additional laboratory studies beyond the usual set of screening laboratory tests. Once the true underlying diagnosis is revealed, more appropriate therapy can be initiated. Additionally, more appropriate anticipatory guidance regarding the expected disease course, response to medications, and any additional risks that therapy may entail can be provided to the family.
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PMID:Recognizing gastrointestinal and hepatic manifestations of primary immunodeficiency diseases. 2087 12

Immunoglobulin light chain amyloidosis is a protein deposition disorder where the precursor protein represents a monoclonal immunoglobulin light or heavy chain. Deposition in viscera results in restrictive cardiomyopathy, nephrotic range proteinuria, demyelinating peripheral neuropathy, hepatomegaly and malabsorption syndrome. Diagnosis requires biopsy with Congo red staining. Invasive biopsies are not required generally. It is essential that after a histologic diagnosis is obtained, the tissue is validated to have an immunoglobulin light chain composition so patients are spared unnecessary chemotherapy. The disease prognosis and patient monitoring are linked to serialized measurement of cardiac biomarkers and immunoglobulin-free light chains. Most patients require cytotoxic chemotherapy. For some patients, this therapy involves stem cell collection and myeloablative chemotherapy; for others, chemotherapy includes an alkylator and a corticosteroid; and for some, it involves addition of a novel agent in the form of an immunomodulatory drug or a proteasome inhibitor. Delays in diagnosis continue to be an obstacle to initiating effective therapy. Early mortality rates remain high. Effective chemotherapy can result in reversal of organ dysfunction and recovery. Reductions in light chain production translate to improved survival.
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PMID:How to manage primary amyloidosis. 2186 40


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