Disaccharide consumption and malabsorption in Canadian Indians.

Twenty-eight Sioux and 29 Saluteaux Indians from a southern and an isolated northern Manitoban community were screened for lactose malabsorption; 55 were also screened for sucrose tolerance. Sixty percent of the subjects were lactose malabsorbers; the incidence increased with age. Lactase deficiency appeared, on the average, between 8 and 15 years of age. About 45% of the subjects were lactose intolerant. Malabsorbers who did not regularly drink milk had the highest symptom scores. The northern subjects consumed significantly more lactose and sucrose than the southern subjects. Two Sioux children were sucrose malabsorbers. It was hypothesized that the significantly greater sucrose consumption by the Saulteaux subjects were responsible for their markedly higher blood glucose curve following the sucrose tolerance tests. Dietary sucrose increases jejunal sucrase activity and the intestinal transport of glucose and fructose. Three of eight children less than 4 years were lactose malabsorbers; hence, medical personnel treating noninjective diarrhea in Indian children should examine for lactase deficiency. It was recommended that vitamin D fortified milk supplements to Indian school children be continued and that the milk be treated so as to reduce abdominal symptoms in the intolerant individuals.

Serum 25-hydroxyvitamin D in infantile rickets.

In small children with nutritional vitamin D deficiency, the serum concentration of 25-hydroxyvitamin D (25-OH-D), the major circulating metabolite of vitamin D, was correlated with the stage of clinical disease. It was low (16 to 20 ng/ml) but within the normal range in the earliest (hypocalcemic) stage of the deficiency syndrome and decreased (less than 15 ng/ml) in the more advanced stages. In patients with familial hypophosphatemia (X-linked dominant), mean serum 25-OH-D concentration was the same as in age-matched normal controls. Evidence is presented that endogenous parathyroid hormone may have a role in the depletion of serum 25-OH0D in deficiency states.

Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.

A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle.

Newborn screening for galactosemia: a new method used in Manitoba.

In July 1983, the Manitoba Perinatal Screening Programme modified its existing procedure for neonatal screening for galactosemia by introducing quantitation of total galactose plus galactose-1-phosphate from dried blood spots using the Multistat centrifugal analyzer. The first 4 years of experience with this method in combination with the Beutler spot test for galactose-1-phosphate uridyl transferase activity is the subject of this report. Of 70,336 newborns screened, 142 (0.20%) met the criteria for clinical follow up. Of these, one child was confirmed to have classical galactosemia and nine children were found to be Duarte/galactosemia genetic compounds. This method of galactosemia screening has proven to be rapid, sensitive, efficient, and the method of choice for mass screening of disorders of galactose metabolism.

Severe mental retardation, cataracts, short stature, and primary hypogonadism in two brothers.

Two severely mentally retarded brothers are described who had a similar facial appearance, cataracts, short stature, minor digital abnormalities, and primary hypogonadism. Their parents were first cousins. Numerous laboratory investigations failed to elucidate a basic metabolic cause for their disorder.

Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers.

We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were < 10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults.

Vitamin D deficiency in a Manitoba community.

OBJECTIVE: Using a cross-sectional survey, to investigate the vitamin D status of a random sample of 80 mother-child pairs (child age 3-24 months) in a Manitoba community with a high incidence of rickets. METHOD: A questionnaire on feeding habits, gestational history, maternal diet and vitamin supplements was administered to mothers in their homes with the assistance of a local interpreter. Venous blood was collected from both mother and child for serum 25-hydroxyvitamin D levels. RESULTS: Of 91% babies initially breastfed, 36% received no formula or milk after weaning and 40% received no vitamin supplements. 24% of mothers took no vitamin supplements during pregnancy and lactation. Knowledge about rickets was poor. In 43% of children and 76% of mothers, serum 25-hydroxyvitamin D levels were below normal range. CONCLUSIONS: Vitamin D levels are low in this population due to lack of fortified dairy products and vitamin D supplements. A public health program should include counseling on rickets and vitamin D supplementation for all infants and pregnant or lactating women.

PIP: In the isolated Island Lake area of northern Manitoba, which has a high incidence of rickets, interviews were conducted with 80 mothers, each with a child at least 2 years old, living in St. Theresa Point and Garden Hill in their homes during June-July 1987 to determine their knowledge and attitudes towards rickets. Nurses obtained blood samples from the women and their young children so the researchers could determine the vitamin D status of both. The mother-child pairs were native Canadians from the Ojibway linguistic group that speaks its own dialect of Ojibway-Cree. Mothers initially breast fed 91% of the children. After weaning, 1/3 of infants received neither infant formula nor milk. No vitamin supplements were given to 40%. Many of the children who did receive vitamin supplements did not receive them regularly. 70% of the mothers did not drink any milk. 24% were milk-intolerant. 24% took no vitamin supplements during pregnancy and lactation. Mothers who did take supplements did not do so regularly. 17% claimed that their skin was sensitive to sunlight. 84% of mothers in one community had never heard of rickets. Most did not know its cause. Neither mothers nor the children were exposed to the sunlight in the summer. When outside, almost all small infants were completely covered to protect them from the elements. The mean 25-hydroxy-vitamin D level was 26.2 nmol/l for the children and 19.8 nmol/l for the mothers. 43% of children and 76% of mothers had a 25-hydroxy-vitamin D level below the normal range. These high levels of vitamin D insufficiency were even more troublesome given that the blood was taken in late June and July when vitamin D levels would be likely to be at their highest. The dearth of vitamin D fortified dairy products and vitamin supplements greatly contributed to the low level of vitamin D status in this area. The findings show a need for public health officials to include education on rickets and vitamin D supplementation for all infants and pregnant or lactating women.

Lactic acidosis in childhood.

Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an "idiopathic" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders.

Effect of abnormal glucose tolerance in pregnancy on infant mortality rate and morbidity. A prospective study.

Ninety-five pregnant women, not previously known to have diabetes but suspected of being at risk for the disease because of obesity, glycosuria, family history, or obstetric history, underwent oral and intravenous glucose tolerance tests in the last trimester of pregnancy. Several methods were used to categorize the degree of abnormality, but none was of value in predicting pregnancy outcome. Perinatal mortality and malformation rates in the offspring of these women were no greater than those of the over-all infant population at this Center and were much lower than those in infants born to women with overt diabetes. Causes of infant morbidity were not increased, with the exception of overweight babies, hypoglycemia, and hypocalcemia. Umbilical vein glucose level correlated significantly with the mothers' blood glucose at the time of delivery. Cord insulin level correlated with infant birth weight and with University Group Diabetes Program number. Birth weight correlated with the degree of the mothers' obesity. It was concluded the documentation of the degree of glucose intolerance in the mother is of little value in predicting fetal outcome but may indicate infants at risk for hypoglycemia and hypocalcemia.

Vitamin-D-deficient rickets in Manitoba, 1972-84.

Vitamin-D-deficient rickets still exists in children in Manitoba and adjacent areas. Between 1972 and 1984, 48 cases were documented at Winnipeg Children's Hospital. The patients ranged in age from 1 to 49 months; 40 were Canadian natives (38 Indians and 2 Inuit), most of whom lived in the Island Lake area of northern Manitoba. Of the 48, 16 had clinical signs of rickets, 12 had tetany due to hypocalcemia and 38 had radiologic evidence of rickets. Hypocalcemia was found in 27, and hypophosphatemia in 19; hyperaminoaciduria was found in 7 of 20. All 48 had elevated serum alkaline phosphatase levels. In addition to rickets, 16 patients aged 12 months or more had evidence of malnutrition. Climate and lifestyle in northern areas of the Canadian midwest result in little or no biosynthesis of vitamin D by solar radiation; therefore, adequate dietary vitamin D intake is essential to prevent deficiency. The diets of pregnant women and infants in these areas are deficient in vitamin D. The authors recommend vitamin D supplements for all pregnant women and infants in areas of risk to eradicate this preventable disease.

Relationships between maternal glucose intolerance and neonatal blood glucose.

Blood glucose changes in 63 infants during the first three hours of life were related to indices of glucose tolerance of their mothers. Of the mothers, 34 had insulin-dependent diabetes, 16 had gestational diabetes, and 11 had minor abnormalities of glucose tolerance. The fasting blood glucose level of the mother and the umbilical cord blood glucose level were both proportional to the rate of glucose decline in the infant after birth which, in turn, was inversely related to the lowest glucose level attained within three hours. Hypoglycemia occurred in 77% of the infants of diabetic mothers, 25% of the infants of mothers with gestational diabetes, and one of 12 (8%) of infants of mothers with minor degrees of glucose intolerance. The blood glucose level at two hours during an oral glucose tolerance test in the mother can be used to predict the probability of her infant having neonatal hypoglycemia.

Increased prevalence of hereditary metabolic diseases among native Indians in Manitoba and northwestern Ontario.

OBJECTIVE: To compare the prevalence of hereditary metabolic diseases in the native and non-native populations of Manitoba and northwestern Ontario. DESIGN: Retrospective analysis. SETTING: Children's Hospital, Winnipeg. PATIENTS: Patients were selected by three methods: laboratory tests designed to screen patients suspected of having a metabolic disease, laboratory investigation of newborn infants with abnormalities detected through screening, and investigation of near relatives of probands with disease. RESULTS: A total of 138 patients with organic acid, amino acid and carbohydrate disorders were seen from 1960 to 1990. Of these, 49 (36%) were native Indians (Algonkian linguistic group). This was in sharp contrast to the proportion of native Indians in the total study population (5.8%). Congenital lactic acidosis due to pyruvate carboxylase deficiency (13 patients), glutaric aciduria type I (14 patients) and primary hyperoxaluria type II (8 patients) were the most common disorders detected. Other rare disorders included glutaric aciduria type II (one patient), 2-hydroxyglutaric aciduria (one patient) and sarcosinemia (one patient). Underreporting, especially of glutaric aciduria type I and hyperoxaluria type II, was likely in the native population. CONCLUSIONS: Hereditary metabolic diseases are greatly overrepresented in the native population of Manitoba and northwestern Ontario. We recommend that native children who present with illnesses involving disturbances of acid-base balance or with neurologic, renal or liver disease of unknown cause by investigated for a possible metabolic disorder.