Hepatic trace elements in the sudden infant death syndrome.
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Biomedical subjects
Publications and source records attributed to G Morrow.
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Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis.
Glucose oxidase test strips were used to evaluate the presence of glucose in nasal secretions and tears in a group of normal children. Substantial amounts of glucose were present in 15 of 17 samples of nasal discharge and 10 of 15 samples of tears. The use of glucose oxidase test strips for diagnosis of cerebrospinal fluid rhinorrhea, therefore, is without merit.
Extracts of hepatic tissue obtained from saline-induced abortuses were analyzed for methylmalonyl CoA carbonylmutase (MM) and propionyl CoA carboxylase (PC) activity. MM activity was similar to control values, which suggests that abortion material may be used to confirm the prenatal diagnosis of methylmalonic acidemia. Confirmation of a presumptive propionic acidemia diagnosis is more tenuous due to the instability of PC and the possibility that saline may induce PC activity.
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Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as "responsive lines" and the other seven lines as "nonresponsive." In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.
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Inborn errors of metabolism can dramatically manifest themselves in the new born period or remain completely undetected. Awareness on the part of the physician, with every attempt being made to arrive at an early diagnosis, is the basis for a favorable outcome. Many approaches to therapy are possible but the most frequently used is that of substrate restriction in the form of dietary control. Frequent monitoring of growth as well as of plasma biochemical analysis can result in adequate nutritional status as well as in normal development.
In this medical age which relies heavily on electronic and technologic advances, the physician is often willing to place unwarranted confidence in laboratory data regarding his patients. In those unusual situations in which the patient is not directly examined, e.g., prospective screening or prenatal diagnosis, treatment errors can be made. These acts of commissions are initiated by interpretation of laboratory data and can result in detrimental effects to the patient. The term iatrogenesis imperfecta has been designated to describe this situation.
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