Galactose-free Diet Research Articles

78 Galactose-1-Phosphate Accumulation in Red Cells of a Neonate

SCHWARTZ, HOLZEL and KOMROWER have demonstrated high levels of galactose-1-phosphate in tissues of newborns deficient in galactose-1-phosphate uridyl transferase activity. Following their recommendations to maintain a known heterozygotic pregnant mother on a galactose free diet, we examined the cord blood of a galactosemic infant. The levels of galactose-1-phosphate were found to be approximately four times normal. At age of ten days, the infant's red cell content of galactose-1-phosphate had increased to seven times normal, even though he was on a galactose free diet. Over the ensuing five weeks, the levels slightly decreased. Intravenous administration of galactose-1-phosphate uridyl transferase in 35 ml of packed normal red cells resulted in prompt disappearance of galactose-1-phosphate and decrease in liver size. Studies of maternal galactose levels in another pregnant woman as well as evaluation of maternal and newborn lactation are in process. (SPR)

Field Test of Galactosemia Screening Methods in Newborn Infants

GALACTOSEMIA is an inborn error of carbohydrate metabolism characterized by the development of malnutrition, cirrhosis of the liver, cataracts, and mental retardation. It is due to absence of the enzyme galactose-1-phosphate uridyl transferase, an enzyme necessary for the normal metabolism of dietary galactose. Galactosemic infants treated promptly with a galactose-free diet develop normally. If, however, the diagnosis of galactosemia is delayed, permanent damage results. In contrast to phenylketonuria, a disorder for which extensive screening programs are already under way, and are mandatory in some states, large-scale screening of infants for galactosemia has not previously been reported, although two methods employing radioactive galactose have been published and their use for screening suggested. 12 The recent development of two new methods for the detection of galactose-1-phosphate uridyl transferase deficiency in whole blood has made possible for the first time direct screening for the enzyme defect at low cost and without the use

Growth and development of children with galactosemia

Summary Sixteen families with 15 living galactosemic children were studied. The physical growth patterns of all but 3 of the children are within normal limits. The intellectual abilities of the parents were normal. All but one of the siblings were also normal. By contrast, 4 of the galactosemic children are mentally defective and one of them is in a state hospital for retarded children. Six others have borderline intelligence and 6 are in the low normal to normal range. Only 3 of the galactosemic children had an intelligence quotient of over 100. Late inauguration of dietary managementwas associated with a greater incidence and severity of mental handicaps. Adherence to a strict galactose-free diet is suggested. It is also recommended that soya products be avoided until additional knowledge is available.

Laboratory Diagnosis of Congenital Galactosaemia at Birth

Although it is impractical to apply the test described in this report to all newborn infants in order to detect sporadic cases of galactosaemia, it would be useful to employ it with newborn infants born into families known to be afflicted with this disorder. The test is based on determination of the enzymic activity which is responsible for normal metabolism of galactose-1-phosphate. Individuals who develop galactosaemia are deficient in this enzyme in the erythrocytes. Blood is obtained from the umbilical cord of the newborn infant and the erythrocytes are incubated in a system containing galactose. In the erythrocytes of individuals who would develop galactosaemia if fed the lactose in milk, incubation of the erythrocytes with galactose leads to accumulation of galactose-1-phosphate in the cells. Details of the method are provided and its application to diagnosis of galactosaemia in a newborn is described. With this information in hand a galactose-free diet can be prescribed and the damaging effect of extraneous galactose avoided.

Inborn errors of metabolism

Dr. Frederick K. Heath: Inborn errors of metabolism may be considered to be the result of an alteration in a specific biochemical reaction or series of reactions. In the case of the mold Neurospora, it has been demonstrated that single genes may control individual biochemical reactions through specific enzymes; that this tendency to control is dominant; and that through gene mutation a recessive altered enzyme specificity may be transmitted under suitable genetic conditions, becoming apparent as an abnormal nutritional requirement.If this information be applied to man, estimated to have tens of thousands of distinct genes, it becomes probable that many inborn errors of metabolism remain to be recognized. Furthermore, a reasonable basis is given for certain features of these disorders, e.g., their relative infrequency, their familial character often associated with consanguinity and their appearance in early life.Although many diseases have been classified as belonging to the group of inborn errors, this clinic considered only four of the better understood examples. Alcaptonuria, characterized by the excretion of homogentisic acid in the urine proportional to the protein intake, is regarded as resulting from a defect in the metabolism of 2,5-hydroxybenzene compounds, particularly phenylalanine and tyrosine. Such urine when acid is normal in color but on standing turns black at the air surface or becomes brown or black when alkaline; it reduces Benedict's solution and turns blue with ferric chloride. Individuals so affected develop ochronosis in later life due to the deposition in fibrous tissues, cartilage and atheromas of a black pigment thought to be a polymer of homogentisic acid. Hence gray, brown or blue pigmentation may be noted in skin and sclerae, and in the aural, nasal and joint cartilages. Osteoarthritis of the intervertebral and larger joints is common. No therapy is known.Congenital galactosemia becomes manifest in infants, who exhibit vomiting, failure to grow or gain weight, hepatomegaly sometimes with positive cephalin-flocculation tests, cataracts, a no galactose an albumin in their urine. On a galactose-free diet all manifestations of the disorder disappear. The nature of the defect responsible for the inability to metabolize galactose is unknown.The Fanconi syndrome is presented as a renal tubular defect characterized by impairment in the reabsorption of glucose, amino acids, inorganic phosphate and possible bicarbonate. The urine tends to be alkaline. Depletion of liver glycogen follows from the loss of urinary glucose. Acidosis, to which the ketosis, amino acid excretion and loss of base all contribute, leads to a negative calcium balance. Replacement therapy is advised.In congenital methemoglobinemia a specific red blood cell enzyme defect in diaphorase, a flavoprotein, has been described which may be responsible for the failure of these individuals to reduce naturally occurring methemoglobin to the ferrous form. Ascorbic acid directly and methylene blue indirectly may aid in this reduction and so modify the severity of the disease.The clinic thus emphasizes the role of genetic factors in determining the enzymic constitution of cells and thereby the metabolic behavior of the whole organism, whether mold or man. It also brings out the need of modification of Garrod's original concept of the relatively benign and non-progressive character of inborn errors of metabolism, since it is now clear that accumulation of even normal metabolic intermediates may have deleterious effects. Finally, the growing significance of the clinical implications of our expanding knowledge of the role of enzyme systems is brought out.

GALACTOSE STUDIES IN AN INFANT WITH IDIOPATHIC GALACTOSE INTOLERANCE

Galactose metabolism has been studied in a group of convalescent children and in one patient with galactosuria, hepatomegaly and splenomegaly, and cataracts. The galactose tolerance of the convalescent infants studied following intravenous injection of the sugar was similar to that observed in healthy adults. Galactose intolerance as measured by test doses of the sugar, persisted in the infant with galactose intolerance despite clinical improvement on a galactose-free diet. Simultaneous administration of glucose or insulin with the galactose accelerated the rate of disposal of the latter partially, but not completely, toward normal. Alcohol did not alter the galactose tolerance of the patient.