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)

Several recent reports have described convulsions in patients with celiac disease, and in some, folic acid deficiency and brain calcifications. A 40-year-old woman with celiac disease, hypocalcemia and generalized tonic-clonic seizures is reported. Hypocalcemia was corrected and convulsions disappeared, but the EEG showed persistent occipital epileptiform activity. Patients with celiac disease and hypocalcemia due to malabsorption are particularly at increased risk for convulsions. Therefore, even a mild degree of hypocalcemia in these patients should be corrected as soon as possible.
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PMID:[Convulsive disorder in celiac disease]. 792 14

A Bull Terrier that was continuously chasing its tail was examined clinically, electroencephalographically, and by computed tomography of the head. The dog was also given test treatments with an anticonvulsant (diazepam) and a pure opioid antagonist (naloxone). The dog appeared to be hysterical and dissociated from its surroundings. Electroencephalography revealed a seizure pattern that was most marked over the temporal lobe, and computed tomography revealed mild hydrocephalus. Diazepam effectively controlled tail chasing, whereas naloxone did not. The dog was discharged on anticonvulsant therapy but subsequently had to be euthanatized when aggression developed. Results of examination and treatment have led the investigators to propose a hereditary mechanism for tail chasing, perhaps related to zinc malabsorption.
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PMID:Tail chasing in a bull terrier. 845 9

Congenital errors of folate metabolism can be related either to defective transport of folate through various cells or to defective intracellular utilization of folate due to some enzyme deficiencies. Defective transport of folate across the intestine and the blood-brain barrier was reported in the condition 'Congenital Malabsorption of Folate'. This disease is characterized by a severe megaloblastic anaemia of early appearance associated with mental retardation. Anaemia is folate-responsive, but neurological symptoms are only poorly improved because of the inability to maintain adequate levels of folate in the CSF. A familial defect of cellular uptake was described in a family with a high frequency of aplastic anaemia or leukaemia. An isolated defect in folate transport into CSF was identified in a patient suffering from a cerebellar syndrome and pyramidal tract dysfunction. Among enzyme deficiencies, some are well documented, others still putative. Methylenetetrahydrofolate reductase deficiency is the most common. The main clinical findings are neurological signs (mental retardation, seizures, rarely schizophrenic syndromes) or vascular disease, without any haematological abnormality. Low levels of folate in serum, red blood cells and CSF associated with homocystinuria are constant. Methionine synthase deficiency is characterized by a megaloblastic anaemia occurring early in life that is more or less folate-responsive and associated with mental retardation. Glutamate formiminotransferase-cyclodeaminase deficiency is responsible for massive excretion of formiminoglutamic acid but megaloblastic anaemia is not constant. The clinical findings are a more or less severe mental or physical retardation. Dihydrofolate reductase deficiency was reported in three children presenting with a megaloblastic anaemia a few days or weeks after birth, which responded to folinic acid. The possible relationship between congenital disorders such as neural tube defects or dihydropteridine reductase deficiency and disturbances of folate metabolism are discussed. Neurological symptoms present in most of these congenital disorders highlight the role of folate in the central nervous system.
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PMID:Congenital errors of folate metabolism. 853 63

The association of celiac disease, epilepsy and occipital calcifications with initial clinical manifestations of epilepsy during the first two decades of life with an often progressive and variable course and clinical expression of malabsorption has recently been described. Two cases of celiac disease with occipital calcifications and a presentation with neurologic symptoms in adulthood are reported. The first case is that of a 40-year-old male who presented recurrent and alternating pure brachial monoparesis and later acute abdominal pain following which celiac sprue was diagnosed. The second case is that of a 53-year-old woman diagnosed with celiac sprue 20 years before, presenting permanent myoclonus in the lower limbs which were progressive in severity, ataxic march and generalized tonoclonic seizures. Both patients had bilateral occipital calcifications on CT and celiac disease was demonstrated on biopsy. The first case also showed marked signal alteration in the white matter on MRI. Celiac disease with cerebral calcifications presents also in adulthood with atypical clinical manifestations. Suspicion of celiac disease may be confirmed by non-invasive methods such as antigliadin and antiendomysium antibody determination. CT imaging is characteristic.
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PMID:[Celiac disease with occipital calcifications: 2 late cases]. 855 80

Since its introduction in 1987, zidovudine monotherapy has been the treatment of choice for patients with HIV infection. Unfortunately it has been established that the beneficial effects of zidovudine are not sustained due to the development of resistant viral strains. This has led to the strategy of combination therapy, and in 1995 treatment with zidovudine plus didanosine, or zidovudine plus zalcitabine, was demonstrated to be more effective than zidovudine monotherapy in preventing disease progression and reducing mortality in patients with HIV disease. Recent work demonstrates an even greater antiviral effect from triple therapy with 2 nucleosides, zidovudine plus zalcitabine with the addition of saquinavir, a new protease inhibitor drug. The HIV protease enzyme is responsible for the post-translational processing of gag and gag-pol polyprotein precursors, and its inhibition by drugs such as saquinavir, ritonavir, indinavir and VX-478 results in the production of non-infectious virions. As resistance may also develop to the protease inhibitors they may be used in combination, and future strategies may well include quadruple therapy with 2 nucleoside analogues plus 2 protease inhibitors. Administration of protease inhibitors alone or in combination with other drugs does raise a number of important pharmacokinetic issues for patients with HIV disease. Some protease inhibitors (e.g. saquinavir) have kinetic profiles characterised by reduced absorption and a high first pass effect, resulting in poor bioavailability which may be improved by administrating with food. Physiological factors including achlorhydria, malabsorption and hepatic dysfunction may influence the bioavailability of protease inhibitors in HIV disease. Protease inhibitors are very highly bound to plasma proteins (> 98%), predominantly to alpha 1-acid glycoprotein. This may influence their antiviral activity in vitro and may also predispose to plasma protein displacement interactions. Such interactions are usually only of clinical relevance if the metabolism of the displaced drug is also inhibited. This is precisely the situation likely to pertain to the protease inhibitors, as ritonavir may displace other protease inhibitor drugs, such as saquinavir, from plasma proteins and inhibit their metabolism. Protease inhibitors are extensively metabolised by the cytochrome P450 (CYP) enzymes present in the liver and small intestine. In vitro studies suggest that the most influential CYP isoenzyme involved in the metabolism of the protease inhibitors is CYP3A, with the isoforms CYP2C9 and CYP2D6 also contributing. Ritonavir has an elimination half-life (t1/2 beta) of 3 hours, indinavir 2 hours and saquinavir between 7 and 12 hours. Renal elimination is not significant, with less than 5% of ritonavir and saquinavir excreted in the unchanged form. As patients with HIV disease are likely to be taking multiple prolonged drug regimens this may lead to drug interactions as a result of enzyme induction or inhibition. Recognised enzyme inducers of CYP3A, which are likely to be prescribed for patients with HIV disease, include rifampicin (rifampin) [treatment of pulmonary tuberculosis], rifabutin (treatment and prophylaxis of Mycobacterium avium complex), phenobarbital (phenobarbitone), phenytoin and carbamazepine (treatment of seizures secondary to cerebral toxoplasmosis or cerebral lymphoma). These drugs may reduce the plasma concentrations of the protease inhibitors and reduce their antiviral efficacy. If coadministered drugs are substrates for a common CYP enzyme, the elimination of one or both drugs may be impaired. Drugs which are metabolised by CYP3A and are likely to be used in the treatment of patients with HIV disease include the azole antifungals, macrolide antibiotics and dapsone; therefore, protease inhibitors may interact with these drugs. (ABSTRACT TRUNCATED)
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PMID:Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. 908 59

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is good, although the optimal antimicrobial regimen is not clearly established. Initial parenteral therapy (tetracycline, penicilline, streptomycine, chloramphenicol, ampicilline) and peroral long-term treatment with trimetoprime-sulphametoxasole, are recommended. As CNS relapse of Whipple's disease may occur after several years, long-term treatment should include antibiotics that are able to cross the blood-brain barrier. The CNS relapse, in contrast to the systemic ones, is resistant to the treatment. Appropriate therapy instituted earlier in the course of the disease is associated with a better neurological outcome. Early recognition can be critical in Whipple's disease because of irreversible neurological sequelae seen later in the course of this potentially treatable condition. In cases with high clinical suspicion in which Whipple's disease cannot be diagnosed with procedures such as jejunal biopsy, antibiotic therapy is recommended. Recovery of an established neurological deficit may rarely occur. Longterm follow-up studies would help to identify the optimal antibiotic regimen and duration of treatment.
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PMID:[Neurologic disorders in Whipple's disease]. 910 28

A 2 5/12-year-old Chinese boy was investigated for refractory seizures and psychomotor regression. His birth history was unremarkable. Generalized seizures occurred at 2 weeks of age with hypocalcemia. They recurred at 7 months of age and have become aggravated since. During hospitalization, in addition to hypocalcemia and hypomagnesemia, he was found to have hypoparathyroidism, cardiomyopathy, and brain atrophy. Excessive renal loss of magnesium, general intestinal malabsorption, or inadequate dietary intake of magnesium were excluded. He was successfully treated with oral supplements of 19-25 mmole/day of magnesium. Over a few months, he made a dramatic progress in development. His hypoparathyroidism and cardiomyopathy gradually resolved. However, intermittent seizures and psychomotor retardation persisted up to his present age of 6 3/12 years. At 4 months of age his younger sister also developed seizures and was found to have isolated hypomagnesemia. This was corrected by oral magnesium and followed by resolution of the seizure. She has developed normally up to her present age of 1 10/12 years. Both patients are currently maintained on oral magnesium oxide.
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PMID:Familial primary hypomagnesemia complicated with brain atrophy and cardiomyopathy. 929 31

We have studied four patients (three male, one female, age range 15-25 years) with epilepsy, bilateral occipital calcifications and latent coeliac disease (CD). The epilepsy started at mean age 7 years, in three cases there were partial seizures and in one case generalized seizure. Three cases had symptoms suggesting malabsorptive syndrome during infancy and one case was diagnosed CD before the onset of seizures. In all cases serologic markers of CD were found, especially antiendomisium antibody, and intestinal biopsy indicated several grades of atrophy. The electroencephalograph (EEG) findings pointed to focal abnormalities in three patients and generalized abnormalities in one patient. In all cases computer tomography (CT) showed bilateral, almost symmetrical occipital calcifications in the cortical subcortical layers. The enhanced CT were unremarkable and magnetic resonance images (MRI) were normal. After diagnosis of CD, all patients followed a gluten-free diet and in three patients a significant reduction in seizure frequency was observed. CD should be ruled out in all cases of epilepsy, cerebral calcifications of unexplained origin and malabsorption syndrome in infancy.
Seizure 1998 Feb
PMID:Epilepsy, cerebral calcifications and clinical or subclinical coeliac disease. Course and follow up with gluten-free diet. 954 26

A six-month-old beagle was presented with a three-month history of failure to gain weight, lethargy, intermittent vomiting and seizures. Hypoglycaemia, portosystemic shunt, lead intoxication, gastrointestinal diseases and hereditary metabolic disorders were considered. Laboratory test results of low serum cobalamin (Cbl) concentrations, anaemia, leucopenia and methylmalonic aciduria while the dog was receiving a balanced commercial canine diet were suggestive of a congenital selective Cbl malabsorption. Treatment with repeated injections of parenteral cyanocobalamin (CN-Cbl) at 50 microg/kg every two weeks corrected the Cbl-deficient state and reversed all the clinical abnormalities. Selective Cbl malabsorption has previously been described in giant schnauzers and border collies and represents a unique readily treatable hereditary metabolic disorder.
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PMID:Persistent cobalamin deficiency causing failure to thrive in a juvenile beagle. 1102 27

Two young females with severe morbid obesity presented with Wernicke's syndrome after Roux-en-Y gastro-jejunum bypass had been performed. The first patient had recurrent vomiting and dyplopia two months post-surgery. Physical examination indicated bilateral ophthalmoparesia with conserved convergence and ataxia. The second patient had frequent vomiting episodes over the previous three months together with lower limb hypotonia, myoclonia and generalised tonicoclonic seizures on two occasions within one year of surgery. In both cases routine blood test, ion levels (sodium, potassium, calcium, phosphates), electroencephalogram and CT scan were normal. Thiamine therapy was instigated on the basis of clinical intuition and the first patient achieved complete remission within 24 hours while the second improved gradually in that two years later only mild lower limb hypotonia and a slight cognitive deficit remains. Erythrocyte transketolase activity determinations were abnormal on two separate occasions for this second patient. Vitamin B1 determinations were not available for the first patient. In conclusion, the restriction in energy intake and the persistent vomiting together with malabsorption induced by the surgical intervention could explain the vitamin deficiency causing Wernicke's encephalopathy. This indicates a need for close monitoring and systematic vitamin supplementation in those patients who undergo bariatric surgery.
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PMID:Wernicke's syndrome after bariatric surgery. 1103 Oct 78


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