A P P R O X I M A T E L Y one haIf the population of the world has survived a period of serious nutritional deprivation during childhood? At the present moment more than 300 million children throughout the world are suffering from varying degrees of malnutrition. Although the severity of this undernutrition has not changed much, the age at which it strikes is changing. As countries begin to industrialize, breast-feeding becomes less and less frequent and malnutrition occurs at an earlier age. For example, in Chile, one of the more rapidly industrializing countries, breast-feeding is rarely practiced and the infant mortality rate during the early months of life remains among the highest in South America. Although many of these children will die, the vast majority will survive and join that half of the world's population which has been inadequately nourished during early childhood. What is the functional result of having survived malnutrition as an infant? Are these children doomed to

Malnutrition and brain development

The activity of acid hydrolases on 13 substrates has been measured in the liver of normal human subjects and of 32 patients with various forms of mucopolysaccharidoses. The most important abnormalities may be summarized as follows:



1
In 3 patients, there was a complete absence of α-fucosidase and an excess of fucose in the mucopolysaccharide fraction. The enzymatic deficiency extended to the brain, lung, kidney and urine. In the liver there was also a large increase in the activity of several acid hydrolases, mostly of the α-galactosidase and of the β-xylosidase.

2
In 5 patients with pseudo-Hurler disease (generalized gangliosidosis), the activity of β-galactosidase, at pH 3.6 was absent and this defect also extended to other tissues. This enzymatic deficiency explains the known accumulation of galactose-rich mucopolysaccharides and of galactosyl-N-acetylgalactosaminyl N-acetyl-neuraminyl)-galactosylceramide (GM1 ganglioside) in the tissues. Several enzymatic activities were greatly elevated, mostly that of α-fucosidase, α-galactosidase and N-acetyl-β-glucosaminidase.

3
In 14 patients with an usual form of Hurler syndrome, the activity of acid β-galactosidase was markedly reduced and this abnormality extended also to the brain and the derm but not to the kidney, spleen and leucocytes. The N-acetyl-β-hexosaminidases, the β-glucuronidase and the α-fucosidase were much more active than normally.

4
In two siblings only, affected by an unusual type of Hurler syndrome, there was a marked elevation of β-galactosidase.





The etiological significance of these findings is discussed and a classification of the mucopolysaccharidoses, based on the activity of the lysosomal enzymes in the liver, is proposed.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1968.tb19570.x

The Abnormalities of Lysosomal Enzymes in Mucopolysaccharidoses

The effects of protein malnutrition on the developing central nervous system in the rat

Differential Regulation of Sphingomyelinase and Ceramidase Activities by Growth Factors and Cytokines IMPLICATIONS FOR CELLULAR PROLIFERATION AND DIFFERENTIATION

The importance of investigating the effects of undernutrition on the developing brain has become more widely recognized in the past few years. Unfortunately, a neurochemical consideration of the problem has scarcely begun. The aim of this chapter is to summarize the present state of knowledge, and an attempt will be made to interest neurochemical readers in the great need which exists for their participation in the debate.

Undernutrition and the Developing Brain

Relative nutritional deprivation was produced in groups of 16 to 21 newborn rats who were all nursed by one dam (deprived group) and compared with control litters containing 10 or less animals. Both groups were weaned at 21 days and thereafter allowed an unlimited supply of food. There was diminished somatic growth in all of the deprived group and, at 2 and 3 weeks, the weight of many of the deprived animals was approximately one-half that of the controls. Brain weight, total brain lipids, cholesterol, and phospholipids were reduced to approximately 80% of the control. Brain cerebrosides were affected to a greater extent than the other lipids, being only 50% of the control values. Histological sections showed less myelin. At 6 weeks, following 3 weeks of ad lib. food intake, the body weight, brain weight, and concentrations of the brain lipids of the initially deprived animals were essentially equal to those in the control animals.

Modification of the schedule of myelination in the rat by early nutritional deprivation

IN 1950, Alvord et al 1 first suggested that the principal neuropathological feature of phenylketonuria (PKU) was a delay in the development of myelin Subsequently, other investigators described areas of pallor in sections of central white matter stained for myelin and retarded myelination of the long tracts 2,3 Similar abnormalities were found in maple syrup urine disease (MSUD) 4-6 Biochemical investigations of the cerebral white matter of patients with these diseases have also indicated that myelin was accumulating at a slower rate than that found in normal brains In both PKU and MSUD, the water content of cerebral white matter was increased and the lipid content reduced 7-10 The reduction of cerebrosides exceeded that of other lipid classes, 9-11 which is to be expected, since the accumulation of this lipid most closely parallels the formation of normal myelin 12 While biochemical studies of this type confirmed prior histological observations,

Development of Myelin in Inherited Disorders of Amino Acid Metabolism: A Biochemical Investigation

SummaryAn analysis of the lipids of various organs of an 11-month-old female dying of Farber's Disease indicated a marked increase in ceramide varying from 8 times normal in the kidney to 66 times ...

Sheila Carr

Papers

Modification of the schedule of myelination in the rat by early nutritional deprivation

Development of Myelin in Inherited Disorders of Amino Acid Metabolism: A Biochemical Investigation

Ceramide and Ganglioside Accumulation in Farber's Lipogranulomatosis.∗: