Ryoji Minami

Vitamin D dependent rickets: Decreased sensitivity to 1,25-dihydroxyvitamin D

A patient with vitamin D dependent rickets with decreased sensitivity to 1,25-Dihydroxyvitamin D was observed. She suffered from bone pain of two years duration beginning at 12 years of age and was found to be suffering from hypocalcemia, secondary hyperparathyroidism and osteomalacia. Laboratory findings revealed normal serum 25-hydroxyvitamin D (27 ng/ml) and markedly elevated serum 1,25-dihydroxyvitamin D (131.9 pg/ml). The hypocalcemia was refractory in spite of administration of 25,000 units of vitamin D2, but therapy with high doses of oral 1α-hydroxyvitamin D3 resulted in significant elevation of the serum calcium level. The clinical findings and course of the patients disease were quite different from those of other patients with vitamin D dependent rickets reported by other authors.

Lysosomal acid hydrolases in established lymphoblastoid cell lines, transformed by Epstein-Barr virus, from patients with genetic lysosomal storage diseases

SummaryLysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases—Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease—and from obligate heterozygotes for these diseases.The respective enzyme activity was undectectable in lymphoblastoid cells from the patients, but not from controls. Obligate heterozygotes could not always be distinguished from controls in lymphoblastoid cells as well as in leukocytes. These results suggest that established lymphoblastoid cell lines are useful material for the enzymatic study of genetic lysosomal storage diseases.

A study of urea-synthesizing enzymes in prenatal and postnatal human liver.

Summary: The urea-synthesizing enzymes of human liver tissues, namely, carbamylphosphate synthetase (CPS, EC 2.7.2.2), ornithine transcarbamylase (OTC, EC 2.1.3.3), arginine synthetase system, argininosuccinase (ASase, EC 4.3.2.1), and arginase (EC 3.5.3.1) were measured between pre- and postnatal periods.Specimens from 67 autopsied human livers obtained from fetuses, premature infants, newborn infants, infants, children, and adults were examined.The mean activities of the enzymes showed an increased pattern for OTC and arginase at fetal life, whereas those of CPS, arginine synthetase system, and ASase of fetal livers showed no significant difference in each stage. Except for arginase, the other four enzyme activities were higher in the postnatal period than those in the fetal life. Arginase activities indicated maximal increase at a gestational age between 28 and 31 weeks and decreased in the postnatal life.Speculation: The present study demonstrated that each of urea-synthesizing enzymes during fetal life developed independently. All five enzyme activities were present in 30% or more of the children even at a gestational age of between 12 and 19 weeks, and the enzyme activities of arginase increased with gestational age until birth. From the results, it may be possible to speculate that urea synthesis is always increasing during fetal periods.

Dubin-Johnson syndrome in a neonate

We described the clinical and biochemical findings in a 32 day-old boy with the Dubin-Johnson syndrome. Only two other patients diagnosed as having the Dubin-Johnson syndrome during neonatal period have been reported in the literature.The ratio of urinary coproporphyrin isomer I of our patient was 97% and that of his parents were carrier level, confirming that increased urinary excretion of coproporphyrin isomer I is of diagnostic value in neonates with the Dubin-Johnson syndrome.

Chronic Niemann-Pick disease with sphingomyelinase deficiency in two brothers with mental retardation

Clinical, biochemical, and electron microscopic studies are pesented in two brothers with Niemann-Pick disease. The clinical features include hepatosplenomegaly and mental retardation without any other neurological signs. Roentgenograms of the chest showed bilateral diffuse reticular infiltration. The amounts of sphingomyelin and cholesterol in liver were increased, and sphingomyelinase activities in both liver and skin fibroblasts were markedly reduced in Case 1. Numerous foam cells and myelin figures were observed in the liver, kidneys, bone marrow, and lymph nodes on electron microscopical examination. These cases were regarded as a variant of Niemann-Pick disease from our investigations as they have mental retardation as an exceptional symptom when they are diagnosed as type B.

Properties of α-l-iduronidase in cultured skin fibroblasts from α-l-iduronidase-deficient patients

SummaryOn DEAE cellulose column chromatography, α-l-iduronidase in cultured skin fibroblasts was resolved into two distinct components, forms A and B. They had similar Km values for 4-methylumbelliferyl-α-l-iduronide, but differed in pH optima and thermal stability. Form B was more heat-stable than form A.Residual α-l-iduronidase activity in Hurler fibroblasts was heat-stable, while that in Scheie fibroblasts was heat-labile, and moreover, that in Hurler-Scheie compound fibroblasts lay intermediate between Hurler and Scheie syndromes. These findings demonstrated that Hurler syndrome, Scheie syndrome and Hurler-Scheie compound were enzymatically distinguishable.

Gene deletions in Japanese patients with Duchenne and Becker muscular dystrophies: deletion study and carrier detection

Fifty unrelated Japanese patients with Duchenne and Becker muscular dystrophy (DMD and BMD) have been studied through use of the dystrophin cDNA probes. The 14‐kb dystrophin cDNA was subdivided into six subclones, and Hind III‐digested DNAs were analyzed by Southern blotting. Of 50 unrelated patients, 20 showed a deletion of one or several of the exon‐containing Hind III fragments (40.0%). These corresponded to 50% (11/22) of BMD patients and 32.1% (9/28) of DMD patients, and the position and extent of deletions were mapped and proven to be more heterogeneous in DMD than in BMD. Both ends of deletions detected by probe 1–2a were common to all six BMD patients, and the 5ends of deletions in probe 5b‐7 were also common to four BMD patients. The phenotypic‐specific deletion in Japanese BMD patients existed in the 5end of the DMD gene, although an apparently similar deletion produced a wide range of clinical courses (BMD phenotype). Three out of eight females in DMD/BMD families were diagnosed as carriers through use of the junctional fragment and dosage analyses of dystrophin cDNA.

Prenatal diagnosis of GM1-gangliosidosis: Biochemical manifestations in fetal tissues

SummaryA prenatal diagnosis of GM1-gangliosidosis was made in a pregnancy at risk, on the basis of a deficiency of β-galactosidase activity demonstrated in cultured aminiotic fluid cells. Biochemical analyses were performed in the aborted fetus. GM1-ganglioside β-galactosidase activity was reduced to 1% of the control value in both the brain and liver of the affected fetus. Lamellar bodies suggestive of membranous cytoplasmic bodies were found in cells of basal ganglions, while the accumulation of GM1-ganglioside in the brain was not remarkable.

Sphingomyelinase activities in cultured skin fibroblasts from patients with Niemann-Pick disease

SummarySphingomyelinase activity in cultured skin fibroblasts from a fetus affected with infantile-type Niemann-Pick disease was 0.5% of control activity; the activities in cells from two patients with adult-type disease (Cases 2 and 3) were 5.0% and 59.0%.Sphingomyelinase activity was separated into three peaks (I–III) by isoelectric focusing. The isoelectric points were 4.5, 4.9, and 5.2 for peaks I, II, and III, respectively. The three peaks in the Case 2 cells were drastically reduced; only a very small peak could be distinguished (pI of 4.7). On the other hand, three peaks were observed in the Case 3 cells. Peak I had a pI of 4.4, peak II a pI of 4.7, and peak III a pI of 5.2. Peak I was found at near normal level, but both peaks II and III were markedly reduced.Sphingomyelinase in the peak I fraction obtained from isoelectric focusing in Case 3 cells was found to have the same Km value as that in control cells.

The mechanism of hyperammonemia in congenital lysinuria

procedures, including multiple bone marrow examinations, with biopsies, and special staining procedures. In spite of her diffuse myelofibrosis, our patient has been tolerating chemotherapy well with the exception of some methotrexate toxicity. Her blood counts have been normal since completion of the induction phase, reflecting adequate bone marrow activity. A bone marrow scan repeated one year after diagnosis showed a slight increase in distribution of the marrow activity. The skull bones, which were not previously visualized, are now demonstrating normal activity. The uric acid level, which was elevated initially and during the first months, is now within normal limits. Subsequent bone marrow biopsies have shown progressive improvement and, recently, complete disappearance of the myelofibrosis. This report also illustrates the usefulness of bone marrow biopsies during investigation of pancytopenic conditions in children.