The spectrum of growth abnormalities in children with 18q deletions.

The objective of this study was to assess the spectrum of growth abnormalities in children with 18q deletions. The growth axis of 50 individuals with a cytogenetically and molecularly confirmed 18q deletion was investigated by determining height, growth velocity, insulin-like growth factor I (IGF-I), IGF-binding protein-3, bone maturation, and response to pituitary stimulants of GH. Children with 18q deletions are short; 64% have a height more than -2 SD below the mean. Affected children also grow slowly; 68% have a growth velocity more than -1 SD below the mean. Half of the individuals have delayed bone maturation. Growth factors are skewed downward; 72% of the IGF-I values and 83% of the IGF-binding protein-3 values are below the mean for chronological age. Similarly, 72% of the children had a reduced or absent response to either of the GH stimulants, arginine and clonidine. In the total group of 50 children only 2 were normal for all parameters evaluated. Short stature and poor growth are common features of individuals with 18q deletions. GH deficiency is common in this cohort of patients and probably plays a role in the short stature seen in many of the affected individuals.

Growth hormone deficiency associated in the 18q deletion syndrome.

The 18q- syndrome is one of the commonest deletion syndromes. Clinical characteristics are variable but may include: hypotonia, tapered digits, "carp-like" mouth, mental retardation, and hearing impairment. Growth failure (GF; both weight and height < 3%) was reported in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 5 18q- syndrome patients, 3 of whom had growth failure (< 3% weight and height); the remaining 2 had normal growth parameters. Laboratory evaluation of growth included measurement of IGF-1, IGFBP-3, bone ages and GH response to pituitary provocative agents. Three patients failed to produced adequate GH following stimulation testing. Of 3 patients with inadequate GH production, 1 had normal growth (above 3%). Only 1 of 5 patients had normal GH production and normal growth parameters. Our findings to date suggest that GH deficiency is common in individuals with the 18q- syndrome. The pathogenesis of this finding is unknown. We postulate that a gene(s) on 18q is involved in GH production.

Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.

Although normal plasma ammonium levels can be maintained in children with inborn errors of ureagenesis, these children are vulnerable to episodic hyperammonemia often resulting in coma and death. To treat such episodes, we designed a therapeutic protocol that included prompt recognition of hyperammonemia, therapy with intravenous sodium benzoate, sodium phenylacetate, and arginine, and nitrogen-free intravenous alimentation. Dialysis was performed if the hyperammonemia was unresponsive to drug therapy. Twelve episodes of hyperammonemia in seven children deficient in carbamyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase were treated; one patient died and the others recovered. In two patients measurement of the distribution of urinary nitrogen revealed that hippurate nitrogen and phenylacetylglutamine nitrogen together accounted for 60 per cent of "effective" urinary waste nitrogen. Successful therapy of episodic hyperammonemia plays an important part in the long-term management of disorders of the urea cycle.

Integrated concentration of growth hormone in juvenile-onset diabetes.

Twenty-four-hour patterns of plasma growth hormone concentrations were evaluated during 50 studies of 42 subjects with juvenile-onset diabetes mellitus. Blood was sampled continuously over 24 h using a portable peristaltic pump under conditions in which subjects remained ambulatory and maintained their daily dietary and insulin regimens. All diabetics showed diurnal patterns characterized by frequent episodes of secretion of growth hormone. The mean 24-h concentration of growth hormone, designated the integrated concentration, was significantly higher among juvenile-onset diabetics (P less than 0.001) than it was in age- and sex-matched nondiabetic populations. Juvenile-onset diabetics younger than 20 yr had significantly higher (P less than 0.005) growth hormone integrated concentrations than did older juvenile-onset diabetics. There was no statistically significant correlation between the integrated concentrations of glucose and growth hormone; thus, the study failed to provide us with support for the hypothesis that elevated growth hormone concentrations in diabetics are a consequence of hyperglycemia. Variability of diurnal glucose concentrations was positively correlated (P less than 0.015) with the growth hormone integrated concentration among juvenile-onset diabetics. Our observations indicate that rapid declines in plasma glucose concentration or episodes of absolute hypoglycemia were significant factors, contributing to both the elevated integrated concentration and the secretory spiking of growth hormone observed in the diabetic population.

Triglyceride integrated concentrations: effect of variation of source and amount of dietary carbohydrate.

The effect of changes in the amount of dietary carbohydrate (45 or 65% of total energy) and in the source of carbohydrate (sucrose or corn syrup) on plasma triglyceride and cholesterol concentrations was studied in eight healthy males. Subjects ingested each of the four formula diets for 10 days in a latin square sequence. Diet-induced response was assessed by measurement of plasma lipid concentrations in blood obtained after overnight fast and by measurement of the mean plasma lipid concentrations--designated the integrated concentration--of blood obtained by 24 hr continuous blood withdrawal. The fasting plasma triglyceride concentration increased significantly during ingestion of the high carbohydrate diet (P less than 0.005) but was not significantly influenced by the source of carbohydrate calories. The 45% carbohydrate diets induced larger meal associated plasma triglyceride variation than 65% diets. Sucrose-containing diets induced significantly higher plasma triglyceride integrated concentrations than corn syrup diets, whether provided as 45% (P less than 0.05) or 65% (P less than 0.005) of total energy. Diet-induced changes in fasting or integrated plasma cholesterol concentration were minimal.