1/139. Cerebral malformation associated with metabolic disorder. A report of 2 cases. A clinical and neuropathological study is presented of two cases each of which showed neuronal heterotopia. Microgyria was also present in one case. One patient was suffering from a degenerative disorder affecting the white matter. The other was a case of Menkes' disease. It is suggested that the antenatal damage may have been caused by an imbalance of the maternal metabolism, the predisposing factor being the mother's carrier state for a metabolic defect. This is the first report of teratogenesis in a case of Menkes' disease. It is also noted that in this case there is interference with the postnatal as well as the antenatal development of the brain. ( info) |
2/139. Sequence variations in the flavin-containing mono-oxygenase 3 gene (FMO3) in fish odour syndrome. Trimethylaminuria is inherited recessively as a defect in hepatic N-oxidation of dietary derived trimethylamine (TMA) which causes excess excretion of TMA so that affected individuals have a body odour resembling rotten fish. Flavin-containing mono-oxygenase 3 (FMO3) catalyses TMA oxidation and mutations in the FMO3 gene have recently been shown to underlie trimethylaminuria/fish odour syndrome. We searched for FMO3 mutations in a previously unreported individual with this disorder using polymerase chain reaction of genomic dna, heteroduplex analysis and direct sequencing of heteroduplex band shifts. We identified a heterozygous missense Pro153-->Leu153 mutation in exon 4. Leu153 has been reported previously as a homozygous mutation in two unrelated siblings with trimethylaminuria and has been shown to result in total loss of FMO3 enzyme activity. In our patient, two further missense mutations were identified on the other FMO3 allele, Val143-->Glu143 and Glu158-->Lys158. Lys158 is known to be a common polymorphism, but has functional significance in reducing enzyme activity by 10%. Glu143 has not been documented previously, but was shown to be a rare polymorphism and may be of further relevance in reducing FMO3 activity. mutagenesis studies and enzyme assays will be necessary to confirm or refute the potential pathogenic significance of Glu143 in this patient, but the mutation Pro153-->Leu153 appears to be a recurrent cause of this distressing metabolic disorder. ( info) |
3/139. Valproate-induced biochemical abnormalities in pregnancy corrected by vitamins: a case report. PURPOSE: Valproate (VPA) is a teratogenic anticonvulsant (AED), but vitamin supplementation has been suggested to limit the effect of VPA on the fetus. Maternal urinary metabolites were monitored to assess the metabolic effects of VPA before and after vitamin supplementation. methods: A pregnant woman with epilepsy receiving VPA and ethosuximide (ESM) was given high-dose multivitamins from 13 to 28 weeks' gestation. Maternal urinary metabolites were measured throughout the pregnancy by gas chromatography/mass spectrometry. RESULTS: Before multivitamin supplementation began, the patient had significantly increased excretion rates of alpha-ketoglutarate, beta-lactate, pyruvate, lactate, methylmalonate, and other metabolites compared with normal pregnant women. During multivitamin supplementation, many previously increased excretion rates decreased significantly. Fetal head growth was normal up to 30 weeks, but then lagged. Bitemporal narrowing was noted at birth. CONCLUSIONS: VPA may cause metabolic abnormalities in pregnancy. Many biochemical abnormalities attributable to VPA in this patient were corrected with high-dose multivitamin supplementation. The specific relation between biochemical abnormalities and VPA teratogenesis remains to be determined. ( info) |
4/139. Sclerochoroidal calcification associated with gitelman syndrome. PURPOSE: To investigate sclerochoroidal calcification in a patient with Gitelman syndrome. METHOD: Case report. Bilateral fundus abnormalities observed in a 58-year-old woman were documented with fluorescein angiography and tomodensitometry. RESULTS: Symmetric yellow-white subretinal lesions were observed in the superotemporal midperiphery of the fundus of each eye. Tomodensitometry examination was consistent with calcium deposition. The medical history included gitelman syndrome. Sclerochoroidal calcification probably resulted from the severe hypomagnesemia. CONCLUSION: gitelman syndrome may be a cause of sclerochoroidal calcification. ( info) |
5/139. Hypokalaemia, hypomagnesaemia and hypocalcaemia in acute non-lymphoblastic leukaemia. Two cases of acute leukaemia, one monoblastic and one myelomonocytic, in which hypokalaemia, hypomagnesaemia and hypocalcaemia were documented, are reported. urinalysis demonstrated renal loss of potassium and magnesium without other evidence of renal tubular dysfunction. The mechanism and clinical significance of these abnormalities are briefly discussed. ( info) |
6/139. Fatal hypermagnesemia. Severe symptomatic hypermagnesemia is a rare clinical problem that predominantly results from excess exogenous magnesium intake in patients with renal failure. This report describes an elderly woman who was given a magnesium-containing cathartic for pre-operative bowel preparation in the context of unrecognized acute renal failure. She subsequently developed one of the highest serum magnesium concentrations ever reported. The hypermagnesemia was successfully treated with continuous arteriovenous hemodialysis, but she ultimately died from complications of hypermagnesemia, that included junctional bradycardia, myocardial infarction and respiratory failure. This case illustrates the importance of ensuring intact renal function prior to administering large quantities of oral magnesium. More specifically, large doses of magnesium salts should be avoided in patients with acute renal failure. ( info) |
7/139. Fits, pyridoxine, and hyperprolinaemia type II. The rare inherited disorder hyperprolinaemia type II presents with fits in childhood, usually precipitated by infection. A diagnosis of hyperprolinaemia type II and vitamin B(6) deficiency was made in a well nourished child with fits. It is thought that pyridoxine deficiency was implicated in her fits and was the result of inactivation of the vitamin by the proline metabolite, pyrroline-5-carboxylate. ( info) |
8/139. Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in italy. Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended. ( info) |
| This article reviews an approach to patients with hypokalemia and metabolic alkalosis using the information obtained from spot urine chloride values, blood pressure determinations, and renin and aldosterone measurements in order to simplify clinical problem solving. ( info) |
10/139. growth and metabolic disturbances in a patient with total parenteral nutrition: a case of hypercalciuric hypercalcemia. hypercalciuria is a common side effect during total parenteral nutrition (TPN). We report a patient with long-term TPN, who demonstrated hypercalciuria, hypercalcemia and growth retardation. The patient is a six-year-old Japanese girl with hirschsprung disease (jejunal agangliosis). jejunostomy was performed at one-month old and since then her nutrition has depended mostly on TPN. When she was 3 years old, continuous TPN was switched to cyclic TPN (on TPN for 11 hrs and off TPN for 13 hrs). The urinary calcium level has been elevated (Ca/Cre ratio, 1.0) since 3 months of age, whereas serum calcium levels stayed within normal range for a while. The serum calcium levels started to elevate to 12 to approximately 13 mg/dl when she was 3 years and 8 months old. She showed growth retardation (height SD score was -4.2SD when she was 5 years and 8 months old) and deteriorated renal tubular function with renal glycosuria, elevated beta 2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase. She was referred to our division for the investigation and treatment of growth disturbance and Ca metabolism. Her bone age was delayed (BA/CA 0.62) and serum IGF-I level was decreased but her GH response to provocation test was normal. Bilateral nephrocalcinosis was revealed by renal echogram and CT scan. By reducing calcium content in TPN solution, the serum and urinary calcium levels could be maintained within normal range and her renal function and growth velocity was improved. ( info) |