Inborn Diseases Research Articles

Bovine GM1 gangliosidosis: An inborn lysosomal disease

The results of studies on GM1 gangliosidosis of Friesian calves are reviewed in the light of present knowledge about inborn lysosomal diseases. Affected calves have poor growth rates and develop signs of incoordination and blindness at about three months of age. The disease is progressive resulting in death at six to nine months of age. Storage of GM1 ganglioside in neurons is associated with reduced activity of tissue β-galactosidase. Evidence is presented suggesting an autosomal recessive mode of inheritance. The implications of these findings relative to diagnosis and control are discussed.

Structure of the three major sialyl-oligosaccharides excreted in the urine of five patients with three distinct inborn diseases: “I cell disease” and two new types of mucolipidosis

The urine of five patients with three distinct diseases (“I Cell disease” and two new types of mucolipidosis) contains sialic acid-rich oligosaccharides in a high amount: 50- to 500-fold the normal. The structure of the major components are as follows: αAcNeu(2→6) βGal(1→4) βGlcNac(1→2) aMan(1→3) βMan(1→4)GlcNac, [ αAcNeu(2→6)] βGal(1→4) βGlcNAc(1→2) αMan(1→3)[ βGal(1→4)GlcNac(1→2) α- Man(1→6) βMan(1→4)GlcNAc and αAcNeu(2→6) βGal(1→4) βGlcNAc(1→2) αMan(1→3)[ αAcNeu(2→6) βGal(1→4) β- GlcNAc(1→2) αMan(1→6)] βMan(1→4)GlcNAc. These results suggest that a deficit in α-neuraminidase is associated to these three different disorders and that an endo-β- D-N- acetylglucosaminidase is able to release sialyloligosaccharides by splitting the sialyglycans of glycoproteins.

Magnetic enzyme membranes as active elements of electrochemical sensors. Specific amino acid enzyme electrodes

The basic principle of the described magnetic enzyme electrodes is a kinetic accumulation of CO2 at the active layer electrode interface. The local pCO2 level is linked to three simultaneous phenomena: substrate diffusion in, enzyme reaction CO2 diffusion out. After a transient state there is a stationary state between the quantity of CO2 produced by the enzyme reaction and the CO2 diffusing from the active membrane to the bulk solution. Continuous determination of free amino acids in biological media is useful in biological processing, fermentation, medicine, pharmaceutical industries and biological research. No methods are presently available for any specific continuous measurement of lysine which is of nutritional importance in protein industrial syntheses; of phenylalanine and tyrosine which have to be monitored in several inborn diseases (phenylketonuria being the most important of them); of arginine and histidine which play a still imperfectly understood part in neurochemistry. The use of decarboxylase bearing membranes as sensors in such measurements could offer several novel advantages: (a) a simple device made of a currently manufactured electrode slightly modified by the use of an enzyme membrane; (b) The absence of any enzymic consumption due to the immobilization and the negligible consumption of substrate during the measurements; (c) The sensitivity which can be sharpened by a systematic study of the membrane parameters; (d) the continuous response of the electrode as long as it is in contact with the substrate solution; (e) the further feasibility as a miniature sensor. The magnetic device introduced allows obviously a convenient use of the enzyme electrode, the active part can be removed and replaced without disturbance for the pCO2 electrode itself. The enzyme electrodes are not only useful at the applied point of view but also at the fundamental point of view by allowing a direct measurement of an intra membrane concentration. The influence of simple structures on enzyme kinetics was studied with enzyme electrodes by our group, in the case of memory and oscillations obtained with enzyme systems.

GLYCOSIDASES IN HUMAN SKIN FIBROBLAST CULTURES

Five glycosidases, alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase and N-acetyl-alpha-glucosaminidase were studied in human skin fibroblast cultures. The pH-dependency, kinetic properties of the enzymes and results of isoelectric focusing and ion exchange chromatography are presented. Techniques suitable for diagnosing inborn lysosomal diseases in skin fibroblast cultures are defined.

PLASMA INFUSION THERAPY FOR HURLER'S SYNDROME

Ever since the first report from Houston of the "plasma infusion" approach to modification of the Hurler's syndrome picture there has been a wide popular feeling that the beginnings of a "treatment" were at hand for this group of inborn error diseases. Intriguing data on alteration of the pattern of urinary mucopolysaccharide excretion, and, to some extent, of the children's clinical manifestations, opened a real hope that a substantial mechanism existed for rendering more normal the skewed metabolism of these patients. In addition, the authors commented that "human plasma infusions . . . seemed to fit the recommendations" given in a previous PEDIATRICS Commentary for theoretically useful therapeutic trials of new materials in patients with inborn error syndromes.

Enzymatic and biochemical diagnosis of inborn lysosomal diseases with neurological symptoms.

Inborn lysosomal diseases with neurological symptoms are reviewed with special reference to the present possibilities of establishing a diagnosis with the help of enzymatic and biochemical methods in

Urinary excretion of acid hydrolases in disease.

Methods were devised for the assay in urine of four acid hydrolases, β-galactosidase, α-mannosidase, N-acetyl-β-glucosaminidase, and -glucuronidase. Highest activities were obtained by assay directly on centrifuged urine. In gel filtration and isoelectric focusing experiments, these enzymes had properties in the urine very similar to those in the kidneys, with the exception of N-acetyl-β-glucosaminidase B, which had only a low activity in the urine. The following findings support the theory that the enzymes derive from the kidneys and not plasma: In mucopolysaccharidosis and pregnancy, levels are high in plasma but low or normal in urine: the relation between the activity levels of the various enzymes is similar in kidney and urine, but not in plasma. The activities of these enzymes were studied in various disorders, including a few inborn lysosomal diseases. A deficiency of β-galactosidase could be demonstrated in mucopolysaccharidosis types II and III, but not type IV. To detect this deficiency, the act...