Kenneth N.F. Shaw

Ultrastructural studies on neuroblastoma. Evaluation of cytodifferentiation and correlation of morphology and biochemical and survival data

Fifteen cases of neuroblastoma, ganglioneuroblastoma and ganglioneuroma were studied by electron microscopy. Ultrastructural features of cytodifferentiation, including numbers of dense core neurosecretory granules (NSG) and neuritic processes, were used to evaluate variation within the neuroblastoma group to determine whether differences in cytodifferentiation exist where light microscopic variations are not evident. These studies revealed that undifferentiated neuroblastomas do show ultrastructural variations not evident by light microscopy. The ultrastructural findings for each case were compared with initial urinary catecholamine excretory patterns, the latter having recently been shown to have valuable prognostic significance. There was a positive correlation, in the undifferentiated neuroblastomas, between increased numbers of NSG and prognostically favorable biochemical excretory patterns. Conversely, low numbers of NSG were associated with an unfavorable biochemical pattern and fatal clinical course. These correlations between ultra‐structural differentiation and the biochemical secretory pattern indicate that ultrastructural evaluation of undifferentiated neuroblastomas would appear to have prognostic value, particularly in cases lacking initial biochemical data or as an adjunct to biochemical studies. Cancer 42:2392–2398, 1978.

Studies of lactose absorption in patients with galactosemia.

Ten patients with galactosemia and six control subjects were given oral lactose loads. Only one child, a patient with galactosemia, failed to hydrolyze lactose and absorb its monosaccharide components. Nine of ten patients with galactosemia hydrolyzed lactose in spite of the fact that lactose had been excluded from their diet since early infancy, which suggested that intestinal lactase does not appear to be dependent upon lactose intake. The results of the sugar tolerance tests and of jejunal enzyme studies indicated that one of the children with galactosemia had an isolated lactase defect.

An approach to management of phenylketonuria

Data are reported on 126 cases of classical phenylketonuria and 14 children with persistent mild hyperphenylalaninemia. An approach to differential diagnosis of children with hyperphenylalaninemia is presented. The method of treatment utilized at the Childrens Hospital of Los Angeles is described. Best results were obtained with early diagnosis and excellent dietary control. While pointed criticism has been leveled at the mandated screening programs for detection of PKU during the newborn period, the data presented in this report substantiate the need for these programs.

Phenylketonuria and scleroderma.

A diagnosis of scleroderma and phenylketonuria was made in an 18-month-old girl. This is the third recorded incidence of the association of these two disorders. Following institution of a low phenylalanine diet, there was softening of the severe sclerodermatous lesions on the trunk and lower extremities, although new lesions have slowly developed on the upper extremities. There has been no clinical or laboratory evidence of systemic scleroderma. Urinary chromatographic studies on 9 other children with scleroderma failed to reveal any distinctive abnormalities in the excretion of amino acids, phenols, indoles, or imidazoles.

Use of aspartame in phenylketonuric heterozygous adults

Asparatame, a new artificial sweetener, was administered to 45 obligate phenylketonuric adults for 28 wk. This new sweetening agent was well tolerated, and no untoward medical or biochemical changes were noted.

Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and cystinuria

This report concerns a patient with severe congenital lacticacidosis associated with proximal renal tubular acidosis and cystinuria. Enzyme studies with cultured skin fibroblasts obtained from the patient revealed zero pyruvate carboxylase activity, but propionyl-CoA carboxylase activity was normal. Administration of various vitamins in large amounts did not improve the clinical condition. In contrast, the patient began to thrive when her diet was supplemented with aspartic acid, asparagine, glutamic acid, and glutamine. The particular dietary treatment used and the biochemical findings merit consideration for management of future cases.

Results of loading doses of aspartame by two Phenylketonuric (PKU) children compared with two normal children

Separate tolerance tests with aspartame at 34 mg/kg-day and phenylalanine at 19 mg/kg-day were compared. The results reveal that slight serum elevation of phenylalanine and tyrosine occurred in the two PKU and the normal healthy adolescents. It would appear that the phenylalanine in the sweetener aspartame is small enough to be of little clinical significance.

Immune functions in methylmalonicaciduria.

A variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria. One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T-cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B-cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations.In vitro exposure of normal cells to methylmalonic acid concentrations up to 50mg/100 ml did not affect chemotactic or lymphoproliferative responses.In conclusion, although B-cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.

Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium

A 6‐year‐old boy presented with recurrent coma associated with hyperammonemia and infection is reported. A liver biopsy revealed decreased ornithine transcarbamylase (OTC) activity (16% of normal). The enzymatic abnormality in the child is supported by the finding of elevated orotic acid excretion in his mother following a protein load, compatible with an X‐linked pattern of inheritance. Since initiation of a dietary arginine supplement, the child has not had recurrent episodes of hyperammonemia.

Peptiduria in polyostotic fibrous dysplasia

Abstract Peptiduria has been observed in two children, a male with polyostotic fibrous dysplasia and a female with the McCune-Albright syndrome. Urine from both patients contained relatively large amounts of a unique array of nine unusual ninhydrin-positive compounds which may be distinctive for their clinical condition. A combination of paper chromatography, preparative thin-layer chromatography, and pH gradient elution with volatile buffers in successive chromatography from anion and cation-exchange resins was used for fractionating the urinary components. Compounds characterized (and their excretion range in milligrams per gram of urinary creatinine) were Gly-Pro (52–440), α-Glu-Hyp (120–536), α-Asp-Gly (11–26), β-Asp-Gly (20–96), Glc-Gal-Hyl (32–73), and Gal-Hyl (50–109). The diketopiperazine of α-Glu-Hyp was demonstrated as an artifact of processing. The relationship of these dipeptides and galactosides are discussed as known structural subunits of the collagen molecule.