Glycogénoses, hyperoxaluries, aminoacidopathies et hyperlipidémies

Abstract

Glycogen storage diseases (GSDs) are inherited disorders that affect glycogen metabolism. The glycogen found in these disorders is abnormal in quantity, quality or both. Liver and muscle have abundant quantities of glycogen and are the most commonly and seriously affected tissues. Because carbohydrate metabolism in the liver is responsible for plasma glucose homeostasis, GSDs that affect mainly the liver usually present as a hepatomegaly and a hypoglycaemia. In contrast, the role of glycogen in muscle is to provide substrates for the generation of ATP for muscle contraction. The predominant clinical features of muscular GSD are muscle cramps, exercise intolerance, susceptibility to fatigue, and progressive weakness. Hyperoxaluria or primary oxalosis is an autosomal recessive disease divided into two forms : type 1, caused by the absence of glyoxylate aminotransferase activity, and type 2 caused by a defect in D-glycerate dehydrogenase/gloxylate reductase. The overproduction of oxalate that is related to these enzyme defect is accompanied by its accumulation in various tissues. Damage to the kidneys, presenting as calcium oxalate nephrolithiasis and nephrocalcinosis, induces progressive renal failure and uraemia treatable by hemodialysis and renal transplantation. Phenylalanine hydroxylase (PAH) deficiency results in an intolerance to dietary intakes of the essential aminoacid phenylalanine and produces a spectrum of disorders including phenylketonuria and non PKU hyperphenylalaninemia. Tyrosinemia encompasses several entities, of which tyrosinemia type 1 (or hepatorenal tyrosinemia) results in the pathological manifestations involving mainly the liver, kidney and peripheral nerves. Classical homocystinuria is an inherited metabolic disorder that arises from defects in either the re-methylation or transsulphuration pathways of homocystein metabolism and leads to skeletal abnormalities, mental retardation and a high risk of vascular disease. Cystinosis is a rare autosomal recessive disorder characterized by the widespread of deposition of cystine crystals in body tissues, particularly in the kidney that results in renal insufficiency treatable by renal transplantation and cysteamine. Familial hypercholesterolemia is characterized by elevated serum cholesterol, tendon xanthomas, xanthelasmas, arcus corneae and premature atherosclerosis. Rheumatological manifestations include acute episodes of polyarthritis and tendinitis. Patients who are homozygous for familial hypercholesterolemia have cardiovascular and rheumatological manifestations more frequently and at earlier age than patients who are heterozygous. Potential myopathy and hepatotoxicity have long been acknowledged as uncommon adverse effects with statins.