Sustained high plasma mannose less sensitive to fluctuating blood glucose in glycogen storage disease type Ia children.

Plasma mannose is suggested to be largely generated from liver glycogen-oriented glucose-6-phosphate. This study examined plasma mannose in glycogen storage disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in the liver. We initially examined fasting--and postprandial 2 h--plasma mannose and other blood carbohydrates and lipids for seven GSD Ia children receiving dietary interventions using cornstarch and six healthy age-matched children. Next, one-day successive intra-individual parameter changes were examined for six affected and two control children. Although there were no significant differences in fasting--and postprandial 2 h--glucose and insulin levels, the mannose level of the affected group was invariably much higher than that of the control group (p < 0.001): the fasting level of the affected group was about two-fold that of the control group; the postprandial-2 h level remained almost unchanged in the affected group, although it was one-half of the fasting level in the control group. Inter-individual analyses revealed that the GSD Ia group mannose level was significantly and positively correlated with lactate and triglycerides levels at both time points (p < 0.01). In each control, mannose levels fluctuated greatly, maintaining strong and significant negative correlations with glucose and insulin levels (p < 0.001). Correlations were lower or nonexistent in GSD Ia children. In individuals with high lactate and triglycerides levels, strikingly high mannose levels never changed against glucose and insulin fluctuations. Plasma mannose is less sensitive to blood glucose and insulin in GSD Ia children. Its basal level and the fluctuation pattern differ by their metabolic activity.

Depressed levels of interferon-gamma and HLA-DR+CD3+ T cells in infants with transient hyperferritinemia.

Familial hemophagocytic lymphohistiocytosis (FHL), which typically has its onset during infancy, is uniformly fatal if not treated. It therefore requires prompt therapeutic intervention. Although hyperferritinemia has been emphasized as a useful marker for FHL, some nonfatal cases in infants with spontaneous remission also manifest with hyperferritinemia. However, distinguishing them is difficult because initial clinical features of these infants are similar. The authors encountered 14 infants with hyperferritinemia (serum ferritin >674 ng/mL), which normalized within 3 weeks following a benign clinical course. The authors compared the levels of HLA-DR+CD3+ T-cell subsets and interferon-gamma (IFN-γ) in the peripheral blood between these infants and FHL cases: one of the authors' own patients and others from the literature. Serum IFN-γ was not detected in infants with hyperferritinemia. Moreover, levels of HLA-DR+CD3+ T cells were extremely depressed. In contrast, serum IFN-γ was elevated and HLA-DR+CD3+ T cells were not depressed in FHL. Measurement of activated T cells and serum IFN-γ might help differentiate FHL in febrile infants with transient hyperferritinemia.

Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy.

Objective To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.

Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth.

BACKGROUND: Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism. OBJECTIVES: We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catch-up growth. METHODS: This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11). Based on parents' choice, 11 SGA children received GH at 0.23 to 0.25 mg/kg/d for 6 months, and at 0.34 to 0.36 mg/kg/d for the subsequent 6 months (GH (+) group). The other SGA children received no GH (GH (-) group, n = 11). We ascertained baseline and posttreatment lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism. RESULTS: Baseline lipid profiles of SGA children and controls were similar. Serum 24S-hydroxycholesterol (marker for cerebral cholesterol metabolism) concentration was 19% lower in SGA children than in controls (P < .05). Compared with baseline, the GH (+) group low-density lipoprotein-cholesterol concentration had decreased by 6.6% during 6 months and 8.8% during 12 months (P < .01), whereas the high-density lipoprotein-cholesterol concentration had increased by 1.7% (P = .07) and 3.3% (P < .01). Serum 7α-hydroxycholesterol (marker for hepatic cholesterol elimination) concentration had increased by 34% at 6 months and 35% at 12 months (P < .01). In addition, 24S-hydroxycholesterol increased by 25% and 26% (P < .001). No marker for cholesterol synthesis or absorption changed. The GH (-) group lipid profiles and oxysterols remained unchanged during the observation period. CONCLUSION: GH activates hepatic and cerebral cholesterol metabolism in SGA children without catch-up growth.

ApoE4 Determines the Reduction in LDL-C After GH Replacement Therapy in Children With an Idiopathic GH Deficiency.

CONTEXT: GH activates the expression of low-density lipoprotein (LDL) receptors, leading to decreased LDL-cholesterol (LDL-C). Apolipoprotein (apo) E4 carriers suppress LDL receptor expression, rendering high LDL-C concentrations. OBJECTIVES: We examined whether GH-deficient children carrying apoE4 exhibited a greater reduction in LDL-C after GH replacement therapy. DESIGN AND SETTING: We determined lipoprotein profiles after 0, 4, and 12 months of GH treatment in children with an idiopathic GH deficiency. We compared the effects of GH treatment on LDL-C by apoE phenotype. SUBJECTS: In total, 66 children with idiopathic GH deficiency and 89 healthy children were classified into subgroups according to apoE phenotype. INTERVENTION: The intervention included GH replacement therapy for 12 months. MAIN OUTCOME MEASURES: The relationship between apoE phenotype and reduced LDL-C induced by GH treatment was measured. RESULTS: Concentrations of LDL-C and apoB were highest in the apoE4/3 group (n = 13), second highest in the apoE3/3 group (n = 46), and lowest in the apoE3/2 group (n = 7), whereas apoE concentrations were highest in the apoE3/2 group and lowest in the apoE4/3 group. The apoE4/3 group had significantly reduced LDL-C and apoB concentrations at months 4 and 12, whereas the apoE3/3 and apoE3/2 groups showed no changes. LDL-C concentrations did not differ among the three groups after 12 months. The trend in apoE concentration did not change among the groups. CONCLUSIONS: Children with a GH deficiency carrying apoE4 had higher baseline LDL-C concentrations and experienced a greater reduction in LDL-C after GH replacement therapy than those without apoE4.