Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia.

Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis, resulting in hepatic energy deficit. Secondary decrease in hepatic argininosuccinate synthetase (ASS1) expression has been considered a cause of hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2 to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for six CTLN2 patients. All the patients' general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia level, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at ASS1 step, but was also associated with an impairment of glutamine synthetase (GS) ammonia-detoxification system in the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT supplement with a low-carbohydrate formula can supply the energy and/or substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes. Histological improvement in the hepatic steatosis and ASS1-expression was also observed in a patient after long-term treatment.

Long-term survival of children with cerebral palsy in Okinawa, Japan.

AIM: The aim of this study was to describe the survival prognosis of children with cerebral palsy (CP) in Okinawa, Japan. METHOD: A cohort study was conducted on all children with CP born between 1988 and 2005 in Okinawa, Japan. Survival proportions were determined with a life table and Kaplan-Meier survival curves were plotted. The effect of each predictor variable was estimated using Cox regression analysis. RESULTS: This study included 580 children with CP (332 males, 248 females). In the cohort, 119 (20.5%) children were classified in Gross Motor Function Classification System (GMFCS) level I, 65 (11.2%) were classified in level II, 40 (6.9%) in level III, 189 (32.6%) in level IV, 166 (28.6%) in level V and GMFCS level was unknown for one. Of the 34 children who died, 29 were classified in GMFCS level V and GMFCS level was unknown for one. Mean age at start of follow-up was 24.5 months (SD 2.6 mo); mean length of follow-up was 8 years 8 months (standard error of the mean 0.214 y). The 5 year- and 18-year survival percentages of the entire cohort were 98% and 89% respectively. In children with CP, significantly lower survival rates were associated with multiple factors, including a birthweight of at least 2500 g (p=0.009), a gestational age of at least 37 weeks (p=0.004), and the most severe gross motor limitation, GMFCS level V (p<0.001). However, multivariate analysis showed GMFCS level V was the only significant predictor variable (p<0.001) for survival of CP. INTERPRETATION: This study is the first to describe survival of children with CP in Japan. Our results are similar to those previously reported in other countries. These results are important in planning adequate provision of social and medical services for individuals with CP.

Mild trigonocephaly with clinical symptoms: analysis of surgical results in 65 patients.

INTRODUCTION: It has been believed that isolated, mild trigonocephaly rarely presents with clinical symptoms. PATIENTS AND METHODS: We diagnosed and operated on 65 patients with mild trigonocephaly and developmental delay up to July 2000. There were 47 boys and 18 girls in our series. All patients had symptoms such as delay in language development, hyperactivity, autistic tendencies, and motor dysfunctions. Their facial features were characterized by a metopic ridge, depressed temples, heel-shaped rather than keel-shaped forehead, and slight hypotelorism. The most important physical sign was the palpable metopic ridge. Most patients did not exhibit any symptoms until they were more than 1 year old. Fifteen patients showed regression in language acquisition and use. Three-dimensional computed tomography revealed the metopic ridge, depressed pterional regions, hypotelorism, and small anterior fossae. Magnetic resonance imaging was performed on all patients and demonstrated no abnormal findings in the brain. Single-photon emission computed tomography (SPECT) was performed on 83% of patients and revealed decreased cerebral blood flow (CBF) in the frontal lobes of 76% of those patients. Decompressive cranioplasty of the frontal bone involving the skull base was performed on all patients. RESULTS: In most (61 out of 65) patients a degree of postoperative improvement in clinical symptoms was noted, especially in behavioral problems. Postoperative SPECT demonstrated increased CBF in the frontal lobes in 95% of the patients. CONCLUSION: Based on these results, it can be postulated that mild trigonocephaly is frequently associated with developmental delays and that these symptoms can be improved to a certain degree by decompressive cranioplasty.