Effects of ketosis on glucose flux in children and adults.

Sequential glucose flux studies were carried out in five normal and six epileptic children and ten adult volunteers using [6,6-2H2]glucose to determine the effect of ketosis on carbohydrate homeostasis in children and adults. All subjects were studied after 14 and 30-38 h of fasting while consuming a normal diet and the epileptic children under 14 h of fasting while consuming an isocaloric ketogenic diet (75% fat wt/wt). Glucose flux, when expressed per kilogram body weight, was inversely correlated with the degree of ketosis in children (P less than 0.001) and in adults (P less than 0.01), but not when both children and adults were considered together (r = 0.078). When glucose flux was corrected for estimated brain weight, the relationship between glucose flux and ketonemia was linearly related in children (P less than 0.001), in adults (P less than 0.02), and when all subjects were considered together (P less than 0.001). The inverse relationship between ketonemia and glucose flux corrected for estimated brain mass is consistent with a partial replacement of glucose by ketone bodies for cerebral metabolism and may provide a more rational means of expressing glucose flux data to take into account the higher brain-to-body ratio in children.

Alloisoleucine formation in maple syrup urine disease: isotopic evidence for the mechanism.

Of the four possible stereoisomers of isoleucine, only L-alloisoleucine and L-isoleucine were found by capillary gas chromatography in the plasma of two maple syrup urine disease (MSUD) patients, one with classical and one with variant MSUD. The relative plasma concentration ratios of L-alloisoleucine/L-isoleucine were 0.795 +/- 0.025 (+/- 95% confidence limits) and 0.637 +/- 0.016 in the classical- and variant-MSUD patients, respectively. The patients were also studied in the postabsorptive state with a 6-hr continuous infusion of L-[15N]leucine. In each patient plasma leucine 15N enrichment approximated plateau after 150 min, and there was rapid appearance of [15N]isoleucine and [15N]alloisoleucine which were identical at plateau, although in variant-MSUD patient [15N]alloisoleucine enrichment did not equal that of [15N]isoleucine until 240 min of infusion. These results offer direct in vivo evidence for the rapid equilibrium of plasma isoleucine and alloisoleucine through keto-enol tautomerization of alpha-keto-beta-methylvalerate.

Topically applied testosterone and phallic growth. Its effects in male children with hypopituitarism and microphallus.

Topical application of 5% testosterone cream for 21 days resulted in enlargement of the penis to normal size for age in five boys with normal XY karyotype who had microphallus and hypopituitarism. In four patients, testosterone cream was applied locally to the penis and in one to an area of skin in the right axilla. Serum testosterone values rose from infantile levels before the start of therapy to normal adult male levels on the last day of treatment. All patients were receiving human growth hormone at the time of therapy with testosterone. No additional acceleration of linear growth and no advance in osseous maturation occurred during or after treatment. Application of testosterone locally for this brief period is a safe, effective, and simple means of stimulating phallic growth. Our findings suggest that topical testosterone causes penile growth predominantly through its systemic action.

Glucose and alanine metabolism in children with maple syrup urine disease.

In vitro studies have suggested that catabolism of branched chain amino acids is linked with alanine and glutamine formed in, and released from, muscle. To explore this possibility in vivo, static and kinetic studies were performed in three patients with classical, and one patient with partial, branched chain alpha-ketoacid decarboxylase deficiency (maple syrup urine disease, MSUD) and compared to similar studies in eight age-matched controls. The subjects underwent a 24-30-h fast, and a glucose-alanine flux study using stable isotopes. Basal plasma leucine concentrations were elevated (P <0.001) in patients with MSUD (1,140+/-125 muM vs. 155+/-18 muM in controls); and in contrast to the controls, branched chain amino acid concentrations in plasma increased during the fast in the MSUD patients. Basal plasma alanine concentrations were lower (P <0.01) in patients with classical MSUD (153+/-8 muM vs. 495+/-27 muM in controls). This discrepancy was maintained throughout the fast despite a decrease in alanine concentrations in both groups. Plasma alanine and leucine concentrations in the patient with partial MSUD were intermediate between those of the controls and the subjects with the classical form of the disease. Circulating ketone bodies and glucoregulatory hormones concentrations were similar in the MSUD and normal subjects during the fast. Alanine flux rates in two patients with classical MSUD (3.76 and 4.00 mumol/Kg per min) and the patient with partial MSUD (5.76 mumol/Kg per min) were clearly lower than those of the controls (11.72+/-2.53 [SD] mumol/Kg per min). After short-term starvation, glucose flux and fasting concentrations were similar in the MSUD patients and normal subjects.These data indicate that branched chain amino acid catabolism is an important rate limiting event for alanine production in vivo.

Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH.

Two three-year-old boys with dwarfism (height ages 1-4/2 and 1-11/12 years) and delayed bone ages (1-4/12 and 1-9/12 years) had normal growth hormone (GH) responses after stimulation and low levels of somatomedin. Unlike patients with Laron syndrome, the two patients generated normal levels of somatomedin after administration of exogenous hGH. Treatment with hGH (2 IU every other day) brought about a significant increase in the growth rate of both patients. The growth rate of the first patient increased from 2 cm/year before treatment to 12 cm/year on therapy. The growth rate of the second patient was 4.5 cm/year before treatment, and 8.3 cm/year while on treatment. The two cases represent a new syndrome of dwarfism which may be caused by secretion of a biologically inactive but immunoreactive GH.

Beckwith-Wiedemann syndrome in a mother and her son.

The Beckwith-Wiedemann syndrome--exomphalos, macroglossia and gigantism--occurred in a mother and her son. The clinical and metabolic features of this syndrome are described. We believe this is the first report of this syndrome affecting a mother and her son. An autosomal dominant pattern of inheritance is suggested.

Inappropriate antidiuretic hormone secretion in an infant with severe pneumonia.

A 6-week-old boy with severe pneumonia developed hyponatremia as a result of the syndrome of inapropriate antidiuretic hormone secretion (SIADH). Cerebral edema and seizures occurred after administration of fluids and diuretics. Fluid restriction and resolution of the pneumonia corrected the severe electrolyte imbalance. The possibility of SIADH should be considered in cases of severe and resistant pneumonia in infancy.