Category Archives: Diameties Mellitus and Other Desorder of Metabolism

The Porphyrias

This heterogeneous group of rare inborn errors of metabolism is caused by abnormalities of enzymes involved in the biosynthesis of haem, resulting in overproduction of the intermediate compounds called porphyrins. Structurally, porphyrins consist of four pyrrole rings. These pyrrole rings are formed from the precursors glycine and succinyl-CoA, which are converted to a-aminolaevulinic acid (a-ALA) in a reacti

Amyloidosis

This is a disorder of protein metabolism in which there is extracellular deposition of insoluble fibrillar protein, either localized or widely distributed throughout the body. Characteristically the amyloid protein consists of f3- pleated sheets that are responsible for the insolubility and resistance to proteolysis. A smaller part of the protein is the amyloid P component (AP), which is derived from normal

Cystinosis

In cystinosis, cystine accumulates in the reticuloendothelial cells. It is inherited in an autosomal recessive manner. The exact mechanism is unknown but it is thought to be a defect of cystine transport across the lysosomal membrane. Three forms are recognized: the infantile form is usually fatal in the first year owing to renal failure; the intermediate form presents in early/young adult life with fever an

Lysosomal Storage Diseases

Lysosomal storage diseases are due to inborn errors of metabolism which are mainly inherited in an autosomal recessive manner. Glucosylceramide lipidoses: Gaucher’s disease This is the most prevalent lysosomal storage disease and is due to a deficiency in glucocerebrosidase, a specialized lysosomal acid l3-glucosidase. This results in accumulation of glucosylceramide in the lysosomes of the reticuloend

Inborn Errors of Amino Acid Metabolism

Inborn errors of amino acid metabolism are chiefly inherited as autosomal recessive conditions. Amino acid transport defects Amino acids are filtered by the glomerulus but 95% of the filtered load is reabsorbed in the proximal convoluted tubule by an active transport mechanism. Aminoaciduria results from: • Abnormally high plasma amino acid levels (e.g. phenylketonuria) • Any inherited disorder that damage

Inborn Errors of Carbohydrate Metabolism

Glycogen storage disease All mammalian cells can manufacture glycogen, but the main sites of its production are the liver and muscle. Glycogen is a high-molecular-weight glucose polymer. In glycogen storage disease there is either an abnormality in the molecular structure or an increase in glycogen concentration owing to a specific enzyme defect. Almost all these conditions are autosomal recessive in inherita

Prevention Trials

Since relatively few deaths will occur in a group of middle-aged subjects, approximately 20000 high-risk patients need to be studied for at least 5 years in a prevention trial to demonstrate whether treating hypercholesterolaemia produces a reduction in death rate. No such large well-designed trial has been performed. During a 5-10 year period of follow-up many more middle-aged subjects will develop non-fatal

MANAGEMENT OF HYPERLIPIDAEMIA

Hypertriglyceridaemia (without hypercholesterolaemia) A serum triglyceride concentration below 2.0 mmol litre-I is normal. In the range 2.0-6.0 mmol litre-I no specific intervention will be needed unless there are many coincident cardiovascular risk factors, and in particular a strong family history of early cardiovascular death. In general, patients should be advised that they have a minor lipid problem, of

Screening

Most patients with hyperlipidaemia are asymptomatic and have no clinical signs. Many are discovered whilst screening high-risk individuals. Whose lipids should be measured? There are great doubts as to whether blanket screening of plasma lipids is warranted. Selective screening of people at high risk of cardiovascular disease should be undertaken including those with: • Family history of coronary hear  dise

Disorders of Lipid Metabolism

PHYSIOLOGY Lipids are insoluble in water, and are transported in the bloodstream as macromolecular complexes. In these complexes, lipids (principally triglyceride, cholesterol and cholesterol esters) are surrounded by a stabilizing coat of phospholipid. Proteins (called apoproteins) embedded into the surface of these ‘lipoprotein’ particles exert both a stabilizing function and allow the particles