Patients suffering from Type I glycogen storage disease frequently develop hepatic tumors. Some of these were classified as carcinoma, with the majority of tumors representing benign adenomata. However, no evidence exists of malignant transformation of adenomata in these patients. Here, we describe the occurrence of a hepatocellular carcinoma in the adenomata-bearing liver of the elder of two sisters suffering from Type I glycogen storage disease at the age of 20 years, 6 years after the diagnosis had been made. Surprisingly, alpha-fetoprotein levels were normal throughout the entire course of this patient, whereas the younger sister had elevated levels despite the absence of malignant lesions. Thus, the clinical significance of alpha-fetoprotein remains unclear in both cases. Nocturnal feeding, although performed continuously over the 6 years after the diagnosis, had obviously failed to prevent the development of hepatic tumors in both patients.

Long-term follow-up shows that the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency benefits from treatment started in the first months of life and that the phenotype may change with age. Additionally, depending on the type of mutations, prenatal damage to the fetus may multiply the clinical abnormalities and thus worsen the prognosis of the disease. In patients initially diagnosed with the mild peripheral form of the disease, therapy with tetrahydrobiopterin should be stopped after some time to test whether hyperphenylalaninaemia was only a transient condition.

Administration of a single dose of tetrahydrobiopterin dihydrochloride, 10--20 mg/kg orally, to a patient with dihydrobiopterin deficiency led to disappearance of clinical symptoms for 4 days, normalization of urinary phenylalanine and serotonin and decrease of elevated neopterin for 2--3 days. A dose-dependent stimulation of serotonin production was observed. A similar effect was noted with even lower doses of L-sepiapterin. The patient is now under monotherapy with tetrahydrobiopterin . 2 HCl, 2.5 mg/kg daily. Other patients with this disease may not respond as well. Results of screening for tetrahydrobiopterin deficiency in 228 cases with hyperphenylalaninemia, including 140 newborns, are reported. There is evidence that biopterin biosynthesis in human kidney and liver proceeds via a dioxo compound and L-sepiapterin.

No abstract

Four neonates who presented with coma secondary to hyperammonaemia resulting in central respiratory failure were treated with peritoneal dialysis for between 16 and 120 hours. Underlying diseases were maple-syrup-urine disease, propionic acidaemia and citrullinaemia in two patients. Clinical improvement was observed in three patients within 16 to 72 hours after institution of peritoneal dialysis. Biochemical analysis revealed a rapid reduction in plasma concentration of leucine, isoleucine and valine as well as their alpha-keto-analogues in the infant suffering from maple-syrup-urine disease. Correction of ammonia, glycine, alanine and propionic acid concentrations was observed in the infant with propionic acidaemia 24-72 hours after institution of peritoneal dialysis. Severe hyperammonaemia (1,000-2,500mumol/l) in two infants with citrullinaemia before peritoneal dialysis was treated successfully in one infant; whereas the second infant showed no clinical improvement despite amelioration of biochemical parameters. Glucose-absorption from peritoneal dialysis solution was in the range of 216-441 mg/kg/h.