Improvements of hypertriglyceridemia and hyperlacticemia in Japanese children with glycogen storage disease type Ia by medium-chain triglyceride milk.

BACKGROUND: Besides profound hypoglycemia with hyperlacticemia, glycogen storage disease type Ia (GSD Ia) presents hypertriglyceridemia that is often resistant to dietary treatment with cornstarch. The present study aimed to evaluate the effects of medium-chain triglycerides (MCT)--which are absorbed via the portal vein without being incorporated into chylomicrons--on hypertriglyceridemia and to explore otherwise metabolic changes in children with GSD Ia. PATIENTS AND METHODS: A 13-year-old boy with GSD Ia who received a dietary treatment with MCT milk after cornstarch administration and two infants also with GSD Ia, ages 6 and 7 months, who received MCT milk after carbohydrate-rich, lipid-poor milk were enrolled. In addition to serum glucose and lactate levels, serum levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were serially determined. Simultaneously, serum levels of total carnitine, free carnitine, acylcarnitine, and ketone bodies were determined to evaluate fatty acid beta-oxidation. RESULTS: Mean glucose level (mmol/l) of patient 1 remained stable, the value being around 4.5, while those of patients 2 and 3 increased to this level from 4.00 and 3.72, respectively. Lactate levels were significantly decreased in all patients. Mean triglyceride levels (mM) of patient 1 decreased from 3.00 to 2.05. Also, triglyceride levels of patients 2 and 3 decreased from 2.74 and 3.15 to 2.13 and 2.70, respectively. HDL cholesterol, acylcarnitine, and ketone body levels increased in all patients after MCT administration, while total and free carnitine levels decreased. CONCLUSION: We describe here the beneficial effects on lipid and carbohydrate metabolisms in three Japanese children with GSD Ia. In light of the unfavorable influence of lipid restriction on growth and development in infancy, dietary treatment with MCT milk may be a better treatment for infants with GSD Ia. Further investigation should be required to confirm the efficacy of MCT milk in GSD Ia.

Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency.

BACKGROUND: The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. RESULTS: The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. CONCLUSION: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.