Mass screening for Wilson's disease: results and recommendations.

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised.

Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics.

Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were seen at local paediatric outpatient clinics in the Miyagi Prefecture.

Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.

The only known Japanese child with biotinidase deficiency was identified by newborn screening in Japan. He has 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity.

Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease.

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats.

Determination of triethylenetetramine in plasma of patients by high-performance liquid chromatography.

A sensitive and simple fluorometric method for the determination of N,N'-bis(2-aminoethyl)-1,2-ethanediamine dihydrochloride (triethylenetetramine) in human plasma by high-performance liquid chromatography is described. Free triethylenetetramine (TETA) obtained by passing the TETA-copper chelate compound through a solid-phase cation exchange resin was converted to its fluorescamine derivative in the presence of ethylenediaminetetraacetic acid to mask the interfering metal ions in the reaction solution, and the derivatives were separated on a nitrile high-performance liquid chromatograph column (Nucleosil 5-CN) using isocratic elution. The plasma levels of TETA were measured in eight patients receiving treatment for excess copper.

Cytotoxicity of galactose, tyrosine and methionine in cultured suckling rat hepatocytes: relation to liver immaturity.

Monolayers of suckling rat hepatocytes cultured for 24 hours were treated with galactose, I-tyrosine and I-methionine. The purpose was to study the reasons for the clinical improvement of patients with neonatal hepatitis after dietary restriction of these nutrients. Galactose, tyrosine, and methionine was cytotoxic on suckling rat hepatocytes, yet had no effect on adult rat hepatocytes.

Microassay for screening newborns for galactosemia with use of a fluorometric microplate reader.

We describe a microassay for measuring galactose (Gal) and galactose 1-phosphate (Gal-1-P) in dried blood spots. After a coupled enzyme reaction involving galactose dehydrogenase (GADH, EC 1.1.

Cerebro-hepato-renal syndrome of Zellweger. Clinical and autopsy findings and a review of previous cases in Japan.

An autopsy case of cerebro-hepato-renal syndrome of Zellweger, which occurred in a 14-year-old Japanese girl, is reported. The autopsy revealed widely distributed cystic changes in addition to renal blastema of both kidneys, and the liver was cirrhotic. The case was complicated by anomalies such as high forehead, strabismus, and partial defect of chorioidea.

Impaired monocyte function in glycogen storage disease type Ib.

Phagocyte (neutrophil and monocyte) function was evaluated in a boy with glycogen storage disease type Ib. Neutrophils were found to be defective in motility and respiratory burst and monocytes showed a defect in respiratory burst but not in motility. These results suggested that the glucose-6-phosphate transport system plays a role in the function of neutrophils and monocytes and that these two phagocytes are different from each other in their energy metabolism for motility.

Follow-up study of a nation-wide neonatal metabolic screening program in Japan. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan.

A nationwide neonatal screening program for phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria, histidinemia and galactosemia was started in Japan in 1977. The total number of infants screened had reached 6,311,754 by March, 1982. A follow-up study revealed the incidence of the disease in Japan: 1/108,823 for PKU; 1/450,840 for hyperphenylalaninemia (HPA); 1/1,577,939 for biopterin deficiency; 1/525,980 for MSUD; 1/1,051,959 for homocystinuria; 1/8,371 for histidinemia, and 1/788,969 for galactosemia type 1.

Distribution pattern of lysosomal granules in fibroblasts of the Chediak-Higashi syndrome.

Cultured fibroblasts from a patient with the Chediak-Higashi syndrome, the mother of the patient, and a normal control were studied by light and electron microscopy. The distribution pattern of PAS-positive and acid phosphatase-containing granules in the cytoplasm differed significantly in the fibroblasts from the patient when compared with those from the mother and control. The granules in the fibroblasts from the patient were clustered in the perinuclear area, whereas the granules in the fibroblasts from the mother and control were dispersed throughout the cytoplasm.

Digestion of asparagine-linked oligosaccharides by endo-beta-N-acetylglucosaminidase in the human skin fibroblasts obtained from fucosidosis patients.

The substrate specificity of human endo-beta-N-acetylglucosaminidase was studied by using the homogenate of cultured skin fibroblasts of fucosidosis patients as an enzyme source. The results indicate that biantennary complex type asparagine-linked sugar chains as well as high mannose type sugar chains are cleaved by the enzyme action. None of the sugar chains with a fucosyl residue on the proximal N-acetylglucosamine of their N,N'-diacetylchitobiose moieties was cleaved.

Metabolic acidosis in patients receiving anticonvulsants.

Blood pH, bicarbonate, PCO2, serum calcium, alkaline phosphatase and red cell carbonic anhydrase were measured in 37 selected patients receiving anticonvulsants. Patients with metabolic acidosis showed a high incidence of hypocalcemia with increased alkaline phosphatase and a significant reduction of carbonic anhydrase-B activity. High iPTH levels were found in 13 patients, but this was not correlated with acid-base balance status.

Lysine intolerance in a variant form of citrullinemia.

An oral loading of lysine (100 mg of lysine-HCL/kg was performed in two patients, 18-and 23-yr-old, with a variant form of citrullinemia. Serum citrulline levels were approximately 10 times higher than control level and lysine levels were within the normal range, in contrast to the classical form of the disease in which serum citrulline is approximately 100 times normal levels and hyperlysinemia is usually present. After lysine loading, lysine levels rose sharply and clearance was decreased.

Urinary glycopeptides of fucosidosis.

Fucosidosis is unique among congenital exoglycosidase deficiencies, because not only oligosaccharides but large amount of glycopeptides are excreted in the urine. The structures of 22 major glycopeptides isolated from urine of a fucosidosis patient were determined. One of the prominent features common to all these glycopeptides was that they all contain 1 fucosyl residue at either C-3 or C-6 position of the N-acetylglucosamine which is linked to asparagine.

Urinary oligosaccharides of fucosidosis. Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins.

Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. Structural studies by sequential exoglycosidase digestion and by methylation analysis revealed that their structures were as follows: Fucalpha1 leads to 6GlcNAc, Fucalpha1 leads to 2Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 2Manalpha1 leads to 3Manbeta1 leads to 4GlcNAc, Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 4Manalpha1 leads to 4GlcNAc, Galbeta1 leads to 4(Fucalpha1 leads to3)GlcNAcbeta1 leads to 2Manalpha1 leads to 6Manbeta1 leads to 4GlcNAc, and Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 4Manalpha1 leads to 6Manalpha1 leads to 6Manbeta1 leads to 4GlcNAc.

Glucose-6-phosphatase activity in liver and blood platelets of two patients with glycogen storage disease type I.

Glucose-6-phosphatase (G-6-Pase) activity in liver and blood platelets of two patients with glycogen storage disease (GSD) type I is described. Both patients had a reduced activity of G-6-Pase in liver. The km value for glucose 6-phosphate (G-6-P) of residual activity in liver of both patients was similar to that of control liver.