Selma E. Snyderman

Enzyme activity in classical and variant forms of maple syrup urine disease

The branched-chain keto acid decarboxylase activity has been determined in skinfibroblasts grown from six subjects with classical maple syrup urine disease and six with variant forms of the disease. The level of activity in the skin fibroblasts reflects the ability of the individual to degrade the amino acids, thus providing an index of the severity of the disease. Observations on sibling pairs indicate that the level of enzyme activity and the severity of the disease are genetically determined. A 3 grade classification is proposed based on tolerance for dietary protein. The metabolic defect in all instances involved the three branched-chain amino acids, providing further support for the concept that this degradative step is under the control of a single gene.

The protein requirement of the premature infant. I. The effect of protein intake on the retention of nitrogen

The effect of high-and low-protein intakes on nitrogen retention in premature infants was studied. Infants fed the higher amount of protein retained much greater amounts of nitrogen. Since weight gain in the two groups was similar, it is concluded that infants fed high-protein diets have accelerated chemical maturation and attain a more mature body composition at an early age.

Protein and Amino Acid Metabolism

The deposition of nitrogen during the perinatal period occurs at a rate greater than that at any other period of life. Although there are few quantitative data in the human, the magnitude of protein synthesis can be appreciated from the following analyses of the nitrogen content of the human fetus: at 6 weeks of age, the total body protein is 0.4 mg; at 20 weeks, the fetus contains 15 g proteinW; at term, the content is 500 g.(16) This increase occurs not only as a result of growth of the fetus, but also because of the change in body composition, which results in a reduction in the water content and an increase in nitrogen.(51) This maturation of body composition does not stop at birth, but continues at a similar rate for the first months of life, then becomes slower and virtually ceases by the age of 4 vears.

Argininemia treated from birth

pregnancy and a normal spontaneous delivery. Apgar scores were 9 and 10 at 1 and 5 minutes. Birth weight was 3.8 kg and physical examination was completely normal. At three hours of age the plasm a arginine level was .4.0 mg/dl (normal average 1.3) and arginase activity was not detectable in the erythrocytes. Repeated /tssays of erythrocyte arginase activity all revealed less than 5% of normal activity. Red blood cell arginine level determined just before the initiation of therapy was 4.22 mg/dl (normal 0.4). The infant was given glucose water until the essential amino acid mixture was started at 18 hours of age; a milk formula was never offered. The mixture was fed in an amount to provid? the equivalent of 2 gm of protein per kg of body weight. It was supplemented with Mead Johnson product 80056* to furnish a total caloric intake of 125 calories/kg. This was the only feeding for the first four months of life. After this, fruits, low protein vegetables and rice cereal were introduced. The diet was later supplemented with various protein-free products such as special bread, cookies, pasta, etc. The natural protein intake has never exceeded 5 grams/day, which provides an estimated 250 to 300 rag/day of arginine.

Molecular basis of phenotypic variation in patients with argininemia

Argininemia is an autosomal recessive disorder caused by a deficiency in the liver-type arginase enzyme. Clinical manifestations include progressive spastic diplegia and mental retardation. While the quality of life can severely deteriorate in most such patients, some do show remarkable improvement in neurological symptoms while on controlled diets. We examined the thesis that differences in clinical responses to dietary treatment are based on molecular heterogeneity in mutant arginase alleles. Genomic DNAs from 11 patients with argininemia were examined using the polymerase chain reaction, cloning, and sequencing. Nine mutations representing 21/22 mutant alleles were identified in 11 patients with argininemia, and four of these mutations were expressed in vitro to determine the severity of enzymatic defects. We found that these mutations accounted for 64% of the mutant alleles in our patients. Based on findings in vitro expression tests, the mutations can be considered either severe or moderate. Patients with at least one moderate mutant allele responded well to dietary treatment; concentrations of plasma arginine were controlled within 300 μM. In contrast, patients with two severely mutated alleles did not respond to dietary treatment and plasma arginine was over 400 μM. Argininemia is heterogeneous at the molecular level. The degree of clinical improvement during dietary treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment correlated with types of molecular defects in the arginase genes.

Diagnosis of metabolic disease.

Use of sophisticated diagnostic procedures for the ever-growing list of metabolic disorders can be reserved for relatively few cases if simple screening procedures are employed in the presence of certain specific clinical signs.

The Essential Amino Acid Requirements of Infants IX. Isoleucine

Acurate knowledge of essential nutrients is a sine qua non of good nutrition. Such information is needed for the prevention and repair of dietary deficiencies arising from food shortages and also in situations where the capacity to handle food is limited by disease states. Evaluation of the requirements for essential amino acids has been peculiarly difficult, since this involves the construction of a diet in which the quantity of a single amino acid can be varied at will. The problem has been approached in several ways: 1. Use has been made of natural proteins deficient in one or another amino acid. This method has very limited applicability, for nature has been singularly unobliging in providing a variety of such proteins. 2. Chemically degraded proteins or protein hydrolysates have been used. A number of procedures can be used to destroy one or more amino acids, which can then be replaced in any quantity desired. Diets constructed from such preparations have the advantage that the amino acids are present for the most part as the natural isomers and that unessential as well as essential amino acids are present. There is, however, the disadvantage that the na

The effect of high caloric feeding on the growth of premature infants

Summary A high caloric feeding in the form of aconcentrated humanized type of prepared infant formula was given to 10 premature infants. It resulted in an increased rate of gain in weight. However, linear growth as measured by the increase in rate of growth of the fibula was not affected by this feeding.

The nutritional therapy of histidinemia

Control of the plasma histidine level in histidinemia is possible with the use of an amino acid mixture free of histidine and a carefully monitored intake of histidine. This regimen is compatible with good physical growth and normal mental development. If further clinical experience demonstrates that widespread nutritional intervention in this disease is warranted, it should be possible to obtain good biochemical control.

Influence of Metabolic Control on Growth in Homocystinuria due to Cystathionine B-Synthase Deficiency

The etiology of the tall stature almost invariably seen in homocystinuric patients is not known. The effect of metabolic control and the role of the GH-IGF system on growth were investigated in 10 patients with homocystinuria. There was a direct correlation between the plasma free homocyst(e)ine and growth velocity SD scores in 18 patient years (r, 0.46;p < 0.05). Plasma 2-y cumulative free homocyst(e)ine and height SD scores were directly correlated (r, 0.82;p < 0.01). Growth velocity SD scores were lower in patients with optimal metabolic control than in those with poorer control (−0.10 ± 0.65 versus 0.95 ± 0.68, p < 0.01). Height SD scores were also lower in the optimally controlled group (−0.01 ± 0.81 versus 1.73 ± 0.88, p < 0.05). GH and GH-related peptides did not deviate significantly from the reference ranges. These findings suggest that overgrowth is directly mediated by homocysteine, that the GH-IGF axis is not involved, and that it may be prevented by optimal metabolic control.