The chemical analyses of mainly splenic, hepatic and cerebral glycolipids of two patients with Gaucher's disease were carried out in the present paper. The patient 1 died at 8months. There was massive infiltration of Gaucher cells in the liver (505g) and spleen (240g). The brain (205g) appeared small, but no definite histological abnormalities could be found. While, the patient 2 showed hypersplenism at age 12 months and neurological regression at age 14 months. Three months after the splenectomy, he died at age 19 months. The weight of spleen, liver, and brain was 340g, 810g and 910g, respectively. It was found that the glucocerebroside accumulated remarkably in both spleen and liver of the two patients, but that the glucocerebroside slightly increased in brain of the patient 2 rather than the patient 1. The splenic and hepatic glucocerebrosides were different from those of brain in the compositions of fatty acids and sphingosine bases. The source of these accumulated glucocerebrosides in the spleen, liver and brain was briefly discussed from the standpoint of the glycolipid metabolism. It was also noted that there was a little difference between the cerebral ganglioside compositions of both patients.
Recent advances in the biochemical research of sphingolipidoses were reviewed, with special reference to various types of gangliosidoses and Krabbe's globoid cell leukodystrophy. A special type of Gm2-gangliosidosis, Sandhoff's disease, was recently found, which is characterized by a deficiency of total hexosaminidase activity, with accumulation of globoside in visceral organs in addition to generalized Gm2-ganglioside storage. Its molecular and genetic basis of enzyme deficiency in relation to classical Tay-Sachs disease is not known. β-Galactosidase deficiency is a common characteristic biochemical abnormality in Krabbe's disease, lactosylceramidosis and two clinical types of Gm1-gangliosidosis. The former two diseases can be diagnosed by deficiency of specific enzymes, galactocerebrosidase and ceramide lactoside β-galactosidase respecti vely, whereas the latter presents an extremely low β-galactosidase activity also for synthetic substrates. At present the fundamental biochemical difference between two types of GM1-gangliosidosis is notestablished yet. More information of the nature on β-galactosidase deficiency is necessary for the understanding of these biochemically interrelated diseases. Enzyme assay methods are now applied for the diagnosis of almost every sphingolipidosis at any stage, including the preclinical and the intrauterine periods, by the use of clinically available materials such as peripheral blood, cultured skin fibroblasts or amniotic fluid cells, although many basic biochemical problems still remain to be solved in future.
Rapid development of analytic procedure for amino acid since 1950 has been accompanied with the discovery of more than forty new disorders of amino acid metabolism. Although the phenotypic condition in metabolic disorder may be influenced by environmental factors, such as excess of amino acid intake, vitamin deficiency, damage of blood-brain barrier and others, the screening of large populations of newborn infants for the metabolic disease has led to the discovery of phenotypic and genotypic heterogeneity in metabolic disorders of amino acid. According to the analytic study of phenylalanine metabolites in serum and urine of the patient with typical and atypical phenylketonuria by using gas-liquid chromatography, it was suggested that there would be several genotypic heterozygotes, homozygotes and also double heterozygotes. The mass-screening of populations with established disease has discovered examples of more genetic disease of metabolism, however, some type of genetic disease associated with partial defect of isoenzymes or defect of an enzyme related to minor metabolic pathway may not be detected by usual screening procedure, because of no chemical abnormality in serum and urine. We may expect the fractionation of the various enzyme deficiencies into spectra of conditions, each with a different alteration in the enzyme.
In experimental hyperaminoacidemia induced in rats by intraperitoneal injection of a single aminoacid, such as phenylalanine, valine, histidine, or methionine, respectively, a significant reduction of protein synthesis in the brain and a significant alternation of the free amino acid pattern in the brain were found. In overflow type of amino acid disorders, an extreme imbalance of amino acids in blood may disturb the transport of certain amino acids into the brain and thereby brain protein synthesis is reduced, consequently the mental retardation may be brought about. In homocystinuria or cystathioninuria, cystine becomes an essential amino acid because of impaired conversion of methionine to cystine. Therefore the dietary nutritional factor in the prenatal and infancy periods may contribute to brain developmen, thereby the degree of mental retardation in these disor ders varies from case to case. Amino acid disorders may be regarded as a sort of malnutrition occurred endogenously.
A long term follow-up study of patients with cerebral palsy has been done in the following manners: (1) 164 cases have been studied prospectively, (2) 78 cases retrospectively, (3) 42 cases longitudinally with periodic examinations. 1) Spastic type was most common (62.8%) during infancy. While it decreased to 28.7%, athetotic and dystonic (dyskinetic) types became most common during school age. 2) Pure rigidity and hypotonic types were not observed beyond the age of 5. 3) Marked modification of the original type such as spastic, rigidity, hypotonic or unclassified type was often noted. During school age this modification advanced toward either spastic or dyskinetic type, no matter what type the patient originally started with. A spontaneous improvement of motor function has been observed in a few cases. 4) Once a patient showed dyskinesis wheather as his original type or as a type modified from the other, further modification was rare and very little clinical improvement was observed thereafter. 5) Modification occured most often in the symptoms related to extrapyramidal system. 6) Dyskinesia usually appeared after the first year of life but the youngest we have observed was 7 months of age. The latest observed was 6 years 3 months of age. 7) It is very interesting to view these modification patterns in relation to the chronological development of the central nervous system. We believe that our observation is useful for prognosticating the patients with cerebral palsy and planning a practical treatment most suitable to each individual.
Manifest bone changes of rickets were detected by X-ray in two cases under anticonvulsant medication. The first case was 3 years 4 months old girl of infantile spasms and hypsarhytmia with partial agenesis of corpus callosum, who have been treated by eleven kinds of anticonvulsants for the past three years. Wrist X-ray examination had been carried out serially: The first X-ray film which was taken at her one year two months old (that is, after ten months of medication) was normal, the second one at her two years nine months old showed slight osteoporosis and rarefaction of metaphysis of long bones, and the third at her three years 3 months old revealed very distinct rachitic changes of skull, rib and long bones of extremities. Serum chemistry was Ca 8.6mg/dl, P 2.8mg/dl, Mg 2.4mEq/L, and urinary excretion of these electrolytes was decreased. Serum alkaline phosphatase was markedly elevated (80K-A units). The second case was two years five months old boy who suffered from frequent generalized convulsions since his 2 months old to whom seven kinds of anticonvulsants had been given. In this case also, the first film at his eleven months old showed no changes but the second one at his 2 years 5 months old revealed the distinct and extansive rachitic changes in long bones. Serum alkaline phosphatase was elevated (55 K-A units), and serum electrolytes was Ca. 10.1mg/dl, P 2.3mg/dl. Vitamin D administration proved to be very effective for normalization of roentgenologic and chemical changes in both cases. Literature on osteomalacia in relation to the anticonvulsant medication was reviewed and the need for the further evaluation of the findings was stressed.
A clinical and electroencephalographic study on 171 children with febrile convulsions was reported. The patients were divided into two groups, i.e. “simple” and “complicated”. About 60% of the cases were male. The initial episodes of convulsions were seen mostly in between 1 and 3 years of age. The family history of febrile convulsion was noted in 33% of the cases and that of epilepsy in 10.6%. The past history of brain damage was noted in 16% of the cases. EEG abnormalities were noticed in 15.15% of simple type and 26.4% of complicated type. The clinical correlates with EEG's were aslfollows: A. Incidence of EEG abnormalities was statistically higher in cases of complicated type, than in simple type Similarly significant were the findings that cases with age of onset over twolyears, history of possible brain damage, and frequent attacks of febrile convulsions presented abnormal EEG more frequently than those with age of onset before two years, negative history of brain damage and less frequent attacks. B. The following three items showed apparent differences in incidence of EEG abnormalities, which was not significant statistically. 1) Family history of epilepsy or febrile convulsions. 2) Association of mental retardation. 3) Persistence of attacks over five years of age. C. There was no correlation between the incidence of EEG abnormality and duration of convulsions or the postictal clinical condition.