Many inborn errors of metabolism are associated with dysmorphic manifestations. In this review, we have attempted to correlate the dysmorphic features with the underlying metabolic defect or its consequences. Most of the defects which we have discussed affect the synthesis or degradation of macromolecules (for example, collagen, elastin, bone mineral, proteoglycans, glycoproteins, and triglycerides). Such defects may affect either a single enzyme or multiple enzymes in specific organelles, such

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... as lysosomes or peroxisomes, or they may affect hormonal control of synthesis and degradation. Examples are also included of defects affecting the catabolism of simple molecules when accumulating metabolites have a secondary effect on macromolecules, as in homocystinuria. In a number of instances, however, the correlation between the biochemical abnormality and the dysmorphic features are not understood. Ultimately, all dysmorphic syndromes will be attributable to a biochemical defect or its effects. The aim of this overview is to provide an insight into the relationship between the two at the present time. The study of inborn errors of metabolism has made substantial contributions to our understanding of biochemistry. It is worthwhile, therefore, to consider whether we can learn anything about the biochemistry of morphogenesis and dysmorphogenesis from studies of those inborn errors which produce dysmorphic features. The first conclusion to be drawn from a survey of inborn errors' 2is that, as a general rule, dysmorphic manifestations can be expected as a result of disorders which affect the synthesis or early steps in the degradation of the large molecules which form the structural framework of cells and extracellular matrix. Many of these macromolecular reactions are under hormonal control and therefore disorders affecting the synthesis and biological action of hormones may also lead to dysmorphic features. Inborn errors affecting the metabolism of simple molecules (for example, organic acidaemias) do not usually lead to dysmorphic features unless there are secondary effects on macromolecules. Major components of the extracellular matrix include collagen, proteoglycans (95% polysaccharide, 5% protein), glycoproteins, elastin, and bone mineral. The architecture of cells is determined by cell membranes and by intracellular structural pro-teins and also by their content of stored macromolecules (for example, triglyceride in normal adipocytes or intralysosomal material in lysosomal storage disorders). Cell membranes are composed largely of phospholipids (phosphoglycerides, sphingomyelin, and plasmalogens), glycolipids, and cholesterol. Disorders affecting the metabolism of some of the macromolecules listed above are well known; others have only recently been recognised. Disorders of collagen and elastin metabolism Collagen is the major fibrous element of skin, bone, tendon, and cartilage and is responsible for their tensile strength. Bone contains mainly type I collagen whereas dermal collafen is approximately 80% type I and 20% type III. Elastin is responsible for the elastic properties of the skin and of the walls of blood vessels.