Shinichiro Arashima

Follow-up study of a nation-wide neonatal metabolic screening program in Japan

A nationwide neonatal sreening 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. The incidences of PKU, HPA, homocystinuria, and galactosemia (type 1) were found to be markedly low in Japan as compared with those in Caucasian countries. There was no great difference in the incidence of MSUD between both. On the other hand, the incidence of histidinemia was higher in Japan.It was found that most of the patients with PKU, HPA, MSUD, homocystinuria, or galactosemia are developing normally due to the early initiation of dietary treatment. These results clearly indicate that the neonatal mass screening program plays a great role in preventing the occurrence of handicapped children.

Leukocyte glutathione peroxidase deficiency in a male patient with chronic granulomatous disease

A male child with chronic granulomatous disease is described in whom glutathione peroxidase deficiency of leukocytes was identified. Stability and activity of G-6-PD and activity of NADPH oxidase were normal. The leukocytes of the parents showed intermediate activities of glutathione peroxidase, suggesting the possibility of autosomal recessive inheritance.

Renal tubular acidosis and skeletal demineralization in patients on long-term anticonvulsant therapy

Three children ranging from seven to 12 years of age from unrelated families were given long-term anticonvulsant therapy including acetazolamide (Diamox). These children had rickets and renal tubular acidosis. Investigations have suggested (1) secondary hyperparathyroidism due to hypocalcemia of rickets and (2) prolonged acetazolamide therapy were responsible for acidosis as a result of reduction of bicarbonate reabsorption in the kidney. A clear-cut recovery from acidosis and rickets was seen in two patients following medication with high doses of vitamin D, an oral supplement of phosphorus, and discontinuance of acetazolamide therapy.

Prenatal diagnosis of I-cell disease

SummaryA pregnancy from a family in risk of I-cell disease was monitored. The fetus was diagnosed as having I-cell disease based on the findings that (1) lysosomal enzyme activities except for acid phosphatase and α glucosidase were clearly elevated in amniotic fluid and were reduced in cultivated amniotic fluid cells, and (2) cytoplasmic inclusions were seen in cultivated amniotic cells by phase contrast microscopy. The accuracy of prediction was confirmed by cultured skin fibroblast of the aborted fetus.

Ultrastructural studies in fetal I-cell disease.

Extract: The skin, brain, lung, liver, and kidney from a 20-week-old fetus who was diagnosed as having fetal I-cell disease by amniocentesis at 14 weeks of gestation were examined by light and electron microscopy. In addition, cultured fibroblasts from the skin were also observed microscopically. Cytoplasmic inclusions with dense polymorphic contents appeared commonly in the capillary endothelial cells in the skin, lung, glomerulus of the kidney, and the epithelial cells of the proximal tubules of the kidney, and sometimes in the hepatocytes of the liver and the nerve and glial cells of the brain. Erythropoietic cells in the liver and circulating erythrocytes contained dense inclusions varying in developmental stages. Fibroblasts of the skin had several clear vacuoles, and cultured fibroblasts were filled with dense inclusions. The dense cytoplasmic inclusions in fetal I-cell disease were light and electron microscopically similar to the residual bodies which are commonly observed in the phagocytic cells.Speculation: In fetal I-cell disease, the cytoplasmic inclusions may first appear as dense bodies in the capillary endothelial cells of fetus as early as 4 weeks of gestation. Material stored in the inclusions may reflect deranged metabolism of the cells. Thus, the morphologic changes of I-cell disease may be due to the deficiencies of intralysosomal enzymes.

α-l-Fucosidase and α-d-mannosidase activity in the white blood cells in the disease and carrier state of fucosidosis

Abstract α- l -Fucosidase and α- d -mannosidase activity in white blood cells from a patient with fucosidosis and her family members were studied. α- l -Fucosidase activity of the patient was completely lacking, whereas the α- l -mannosidase activity was increased and relative thermostability of this enzyme was also observed. Apparent K m value of α- d -mannosidase was similar in the patient and the control. When the ratio of α- l -fucosidase to α- d -mannosidase activity was calculated, the value of the parents was intermediate between that of the patient and the control.

Ornithine transcarbamylase, an isoelectric point (pI) isozyme in human liver and its deficiency.

Abstract The crude extract of human liver ornithine transcarbamylase, obtained from a patient with hyperammonemia due to enzyme deficiency, was studied by the isoelectric focusing method. The activity of ornithine transcarbamylase in the patient at pH 8.0 was only slightly reduced. After electrolysis, two main peaks which were isoelectric at pH 3.2 and pH 4.4 were observed in the control, while only one peak at pH 2.8 was found in the patient.

Lysine intolerance in a variant form of citrullinemia.

Summary: 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. Blood ammonia rose approximately 2.5 times. Lysine, citrulline, and arginine were markedly elevated in urine, collected 90–210 min after the lysine loading. Baseline homocitrulline and homoarginine excretion was elevated and increased further after the load.Speculation: Lysine tolerance was impaired in two patients with citrullinemia, although baseline lysine levels were normal. Lysine seemed to be catabolized along the alternate urea cycle: lysine-homocitrulline-homoarginine-urea. Hyperammpnemia was aggravated, suggesting competition between lysine and ammonia for α-ketoglutarate and inability to remove ammonia completely by these two alternate pathways

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. Anticonvulsant drugs seemed to inactive carbonic anhydrase-B activity. Metabolic acidosis might be one of the factors causing a disturbance of calcium metabolism in these patients.

CEREBRO‐HEPATO‐RENAL SYNDROME OF ZELLWEGER

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. So far there have been only 10 reported cases of cerebro‐hepato‐renal syndrome of Zellweger in Japan.