Philip F. Benson

Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome.

We have assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunters syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of alpha-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that we were able to assess. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.

A Form of Mucopolysaccharidosis with Visceral Storage and Excessive Urinary Excretion of Chondroitin Sulphate

A case of mucopolysaccharidosis is described, in which the principal glycosaminoglycan stored in the liver and excreted in the urine was chondroitin sulphate. Both isomers were present in equal amounts. The clinical features were similar to those of the Hurler syndrome or mucopolysaccharidoses type I (McKusick 1966).

Congenital Dysphagia Resulting from Dysfunction of the Pharyngeal Musculature A Clinical and Radiological Study

Congenital dysphagia due to paresis or inco‐ordination of the pharyngeal musculature was studied in five children. The clinical features of excessive oropharyngeal secretions, cyanosis and choking attacks during feeds in the first days of life closely resembled those of congenital tracheo‐oesophageal fistula.

Suppression by Actidione of Development of Rat Liver L-Tyrosine : 2-Oxoglutarate Aminotransferase Activity

The development of L-tyrosine : 2-oxoglutarate aminotransferase in newborn rats is suppressed by actidione (cycloheximide), an inhibitor of protein biosynthesis, administered immediately after birth.

The effect of dextran infusions on glycosaminoglycan excretion in the Sanfilippo syndrome.

Infusion of a dextran solution of equivalent osmolality to plasma into a patient with the Sanfilippo syndrome caused an increased excretion of uronic acid. This increase was less than that obtained previously, when an equal amount of plasma was infused into the same patient. Moreover, there were no significant changes in the ratio of larger to smaller glycosaminoglycan fragments or in the sulphate/uronic acid ratios, in contrast to the changes noted subsequent to plasma infusion. It is concluded, therefore, that in this case infusion of dextran was not as effective as plasma in inducing a temporary increased mobilisation of pathological glycosaminoglycans.

INCREASED EXCRETION OF LOW MOLECULAR WEIGHT GLYCOSAMINOGLYCAN FRAGMENTS FOLLOWING PLASMA INFUSION IN A CASE OF HUNTER SYNDROME

A 3-year old boy with the severe form of Hunter syndrome (MPS IIA), was treated by the infusion of plasma from 6 pints of pooled blood over a period of 2 days. Total 24hr uronic acid excretion increased fourfold immediately following infusion. This increase was almost entirely due to glycosaminoglycan fragments not precipitated with 9-aminoacridine although there was also a small increase in the amount of precipitated (polymeric) material. There was an increase in the proportion of glycosaminoglycan fragments of lowest molecular wt. coupled with a decrease in intermediate sized fragments shown by Sephadex gel filtration. Degree of sulphation was stable before infusion, then fell and rose again in a cyclical pattern after treatment. Larged sized precipitable glycosaminoglycan fragments had a noticably higher content of glucosamine than the smaller supernatant fragments suggesting that the heparan sulphate glycosaminoglycans were less readily degradable than dermatan & chondroitin sulphates. This pattern of response differed qualitatively from those we have found in 2 types of (MPS III) (Dean et al, 1973.)