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Galactokinase is an essential enzyme in the metabolism of galactose. Patients with deficiencies in galactokinase exhibit early-onset cataracts. We examined the sequence of the human galactokinase gene (GK1) from 13 patients exhibiting galactokinase deficiency and identified 12 novel mutations. One of the mutations occurred in six of the 13 probands examined, and the remaining 11 were unique mutations. Expression of each of the mutant GK1 genes in Xenopus oocytes resulted in very low galactokinase activity levels. These results provide important information regarding the types of GK1 mutations that occur in the human population.

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A preliminary evaluation of the molecular basis of phenylketonuria (PKU) in Costa Rica was made by performing mutational analyses in the six PKU families identified to date. These studies revealed the presence of the previously reported European mutations IVS1nt5, L48S, E221G and IVS12ntl as well as the novel mutation IVS7nt3. The combined use of the STR, VNTR and XmnI polymorphic systems for the PAH gene resulted in a discriminant distribution of haplotypes among normal and mutant chromosomes and suggests its potential usefulness for future diagnostic applications in Costa Rican PKU kindreds. This is the first report of a genetic analysis in a Central American PKU population.

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The mechanism of the observed decrease in the plasma concentration of several amino acids in the presence of high levels of Leu has remained unexplained. In the present study a decrease in the plasma concentration of Ile, Val, Phe, Tyr, Met, Ala, Pro and Gly was observed after the intraperitoneal injection of Leu to weanling rats. Decreases in net intracellular concentrations in muscle accompanied the decrease in plasma of all of these amino acids except Pro and Gly. An increase in the distribution ratio muscle/plasma was observed exclusively for Gly after administration of Leu or of a non-insulinogenic transport system L analogue. Diazoxide suppressed the Leu-induced decreases in plasma and muscle intracellular concentrations of Ile and Val as well as of Pro in plasma. An increase in the distribution ratio liver/plasma was observed for Pro and Gly in the absence but not in the presence of diazoxide. All the above changes were statistically significant. Hence insulin probably mediates Leu effects, promoting an increased utilization of Ile and Val in muscle and of Pro in liver. A more direct effect of Leu appears to be involved in the apparent increased utilization of Phe, Tyr and Ala in the same tissue. Gly depletion in plasma can be explained by its trapping by inhibitory action of Leu on the exodus of Gly through transport system L.

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The mechanism of the depletion of several plasma amino acids in PKU has remained unexplained. In the present study, a statistically significant decrease in the plasma concentration of several amino acids was observed 2 h after the intraperitoneal injection of Phe to weanling rats. The pattern was very similar to the one observed in PKU patients. Statistically significant increases in the distribution ratios liver/plasma and, mainly, muscle/plasma ratios accompanied in most of the cases the corresponding decreases in plasma concentrations. Equimolar injection under the same conditions of the non-insulinogenic transport system L analogue, the a(+/-) isomer of the 2-aminonorbornane-2-carboxylic acid, produced, in a parallel effect to Phe, statistically significant increases in the distribution ratios of Ala and Gly, and probably of Pro in muscle, as well as of Ala in liver. These results seem to indicate that the high intracellular Phe attained inhibits the exodus of small neutral amino acids through system L, causing their depletion in plasma and ultimately in the brain. This effect may be additive to the inhibition by Phe of the entry of bulky neutral amino acids at the level of the blood-brain barrier. Further study is needed to assess the relevance of these effects to PKU.

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The amino acid profile was studied in individual random samples of urine from 1147 normal schoolchildren and 1074 exceptional children: 628 with mental retardation, 332 with hearing and speech defects and 114 with visual defects as well as in 673 patients with mental disorders. Laboratory procedures included chemical tests and one-dimension paper- electro- and column-chromatography. Phenylketonuria was found in a mentally retarded girl and in one of her brothers; iminoglycinuria in a mentally retarded boy and heterozygote cystinuria in a man with manic-depressive psychosis. The percentage of high excretors of beta-aminoisobutyric acid (B-AIB) in the controls (4.88%) was similar to previous findings in the Caucasian race. The children with hearing and speech defects showed a number of high excretors of B-AIB significantly lower (X2 = 5.32; p less than 0.025) and the children with visual defects a number of hyperglycinurias significantly higher (X2 = 9.19; p less than 0.05). Previous non-consistent findings on the excess of high excretors of B-AIB in Down's syndrome were not confirmed in this study. These results suggest a relationship between transport defects in the plasma membrane and pathological disorders in some of the cases screened.

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PIP: The outcome of administering ORT (oral rehydration therapy) to 62 infants admitted to a Costa Rican hospital with acute rotavirus or bacterial diarrheas and with 5-10% dehydration was described. 94% of the infants were successfully treated by administering only ORT. There were no significant differences in the success rates for rotavirus diarrhea patients and for various bacterial diarrhea patients. Success rates were 92% for rotavirus patients, 93% for Escherichia coli patients, 96% for idiopathic diarrhea patients, and 100% for salmonella and shigella patients. Upon admission, the average duration of diarrhea was 2.9 days, vomiting was present 88% of the cases, and all patients exhibited some signs of dehydration. The infants were administered the oral formula recommended by the World Health Organization. Patients received 400 ml of oral solution followed by 200 ml of water. The treatment was repeated until skin tuger was normal. 34% of the infants were rehydrated within 6 hours and 76% within 20 hours. Patients were admitted with a variety of electrolyte abnormalies. 24% had hyponatraemia, 27% had hypokalaemia, and 23% had hypernatraemia. Sodium levels were improved within 24 hours for all patients except for 5 hyponataemia patients. Although rotavirus patients had higher stool glucose concentrations than the other patients, they apparently absorbed enough of the solution to rehydrate successfully. Specific data on changes in weight, plasma protins, hematocrit, blood composition, and stool composition and on therapeutic failures was provided. Investigators concluded that ORT was a safe and effective form of therapy for both rotavirus and bacterial diarrhea and for severe cases of dehydration.^ieng

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In a randomised double-blind trial, 51 5--10% dehydrated infants were rehydrated with oral electrolyte solutions containing sucrose or glucose. Most infants in both groups were successfully rehydrated, but the sucrose solution produced a slower correction of electrolyte abnormalities and a higher percentage of patients who needed more than 24 h of therapy. Where there is adequate knowledge of the oral therapy method sucrose can substitute for glucose in many cases; where there is a choice glucose is recommended.

PIP: 51 infants aged 3 to 12 months with dehydration due to acute watery diarrhea were randomly assigned to either the glucose or sucrose oral therapy group on admission to the hospital. Oral rehydration and maintenance without any intravenous fluids was successful in 100% and 92% of patients in the glucose and sucrose groups respectively, as evidenced by the subjects' weight gain, fall in plasma proteins and hematocrit, and disappearance of clinical signs of dehydration. There was a greater improvement in mean HC03 in the glucose group than in the sucrose group. Both groups exhibited decline in mean serum osmolarity. The 2 oral treatment failures in the sucrose group occurred in patients who could not absorb the solutions adequately. This study shows that oral therapy with sucrose is less efficient than oral therapy with glucose. However, in areas where only sucrose is available and where knowledge and means of using oral therapy exist, the oral sucrose solution can be used to treat most infants with diarrhea and 5 to 10% dehydration.

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A number of previously unrecognized abnormal metabolites have been identified and quantitated in the urine of a patient with an inherited deficiency of propionyl-CoA carboxylase. These included the isoleucine metabolites 2-methyl-3-hydroxybutyric acid and 2-methylacetoacetic acid. These isomers 3-hydroxyvaleric acid and 3-oxovaleric acid were found, which may be products of the condensation of propionyl-CoA with acetyl-CoA catalyzed by 3-oxoacyl-CoA thiolases. Following a load of isoleucine, 2-methylbutyrylglycine was identified. This metabolite has not previously been observed in man.

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