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Metabolic Disease

Major Classes Of Metabolic Disorders



Cells are constructed from four major types of molecules: carbohydrates, proteins, fats, and nucleic acids. The metabolic pathways involving each are

Disease Defective Enzyme or System Symptoms Treatment
Disorders of Amino Acid Metabolism
Phenylketonuria (PKU) phenylalanine hydroxylase severe mental retardation screening; dietary modification
Malignant PKU biopterin cofactor neurological disorder
Type 1 tyrosinemia fumarylacetoacetate hydrolase nerve damage, pain, liver failure liver transplantation; preceding enzyme inhibitor plus dietary modification
Type 2 tyrosinemia tyrosine aminotransferase irritation to the corneas of the eyes diet with reduced phenylalanine and tyrosine content
Alkaptonuria disorder of tyrosine breakdown progressive arthritis and bone disease; dark urine
Homocystinuria and Hyperhomocysteinemia cystathionine-β-synthase or methylenetetrahydrofolate reductase or various deficiencies in formation of the methylcobalamin form of vitamin B12 hypercoagulability of the blood; vascular eposides; dislocation of the lens of the eye, elongation and thinning of the bones, and often mental retardation or psychiatric abnormalities vitamin B12, folic acid, betaine, a diet limited in cysteine and methionine
Maple Syrup Urine disease branched-chain ketoacid dehydrogenase complex elevations of branched-chain amino acids, characteristic odor of the urine, episodes of ketoacidosis, death thiamine; careful regulation of dietary intake of the essential branched-chain amino acids
Disorders of Organic Acid Metabolism
Propionic Acidemia propionyl-CoA carboxylase generalized metabolic dysfunction; ketoacidosis; death diet with limited amounts of the amino acids which are precursors to propionyl-CoA
Multiple Carboxylase deficiency pyruvate carboxylase and 3-methylcrotonyl-CoA carboxylase biotin
Methylmalonic Acidemia methylmalonyl-CoA mutase; defects in the enzyme systems involved in vitamin B12 metabolism supplementation with large doses of vitamin B12; diet
Disorders of Fatty Acid Metabolism
Hyperlipidemia and hypercholesterolemia regulation or utilization of lipoproteins cardiovascular disease dietary modifications and use of drugs that inhibit fatty acid synthesis.
Fatty Acid Oxidation disorders very long chain acyl-CoA dehydrogenase; long chain hydroxyacyl-CoA dehydrogenase; dehydrogenase; medium chain acyl-CoA dehydrogenase; short chain acyl CoA dehydrogenase; short chain hydroxyacyl-CoA dehydrogenase low blood sugar (hypoglycemia); muscle weakness; cardiomyopathy avoidance of fasting, intravenous glucose solutions; carnitine; medium chain triglycerides
Glycogen Storage diseases defects in glycogenolysis liver enlargement or damage; muscle weakening or breakdown; disturbed renal tubular function; risk of brain damage
Galactosemia galactose-1-phosphate uridyl transferase liver failure in infancy newborn screening; milk avoidance
Congenital Disorders of Glycosylation defects in the enzymes that build the carbohydrate side-chains on proteins quite variable; multisystem
Disorders of Purine and Pyrimidine Metabolism
Purine Overproduction imbalance between purine synthesis and disposal gout
Lesch-Nyhan syndrome hypoxanthine phosphoribosyl-transferase defective salvage of purines; increase in the excretion ofuricacid; brain neurotransmitter dysfunction; severe spastic movement disorder; self-injurious behavior allopurinol (does not treat neurological symptoms)
Lysosomal Storage Disorders
Gaucher disease Types I and II cerebrosidase enlargement of the spleen and liver; painful and crippling effects on the bones; severe brain disease and death (Type II) enzyme replacement (Type I)
Tay-Sachs disease beta-hexosaminidase A neurological disorders; enlarged head; death in early childhood
Table 1 (continued on next page).

Disease Defective Enzyme or System Symptoms Treatment
Lysosomal Storage Disorders [CONTINUED]
Fabry disease α-galactosidase severe pain; renal failure; heart failure enzyme replacement
Hurler syndrome, Hunter syndrome α-iduronidase (Hurler syndrome);iduronate sultatase (Hunter syndrome) iduronate sultatase (hunter syndrome) enlargement of the liver and spleen; skeletal deformities; coarse facial features; stiff joints; mental retardation; death within 5-15 years enzyme replacement
Sanfilippo syndrome enzymes for heparan sulfate degradation enlargement of the liver and spleen enzyme replacement
Maroteaux-Lamy syndrome arylsulfatase B progressive, crippling and life-threatening physical changes similar to Hurler syndrome, but generally with normal intellect
Morquio syndrome galactose 6-sulfatase; β-galactosidase truncal dwarfism; severe skeletal deformities; potentially life-threatening susceptibility to cervical spine dislocation; valvular heart disease
Disorders of Urea Formation
carbamyl phosphate synthetase deficiency; ornithine transcarbamylase deficiency, citrullinemia, argininosuccinic aciduria hyperammonemia; mental retardation; seizures; coma; death limitation of dietary protein; phenylacetate; liver transplantation
Disorders of Peroxisomal Metabolism
Refsum disease branched-chain fatty acid buildup neurologic symptoms
Alanine-glyoxylate transaminase defect alanine-glyoxylate transaminase oxalic acid increase; organ dysfunction; renal failure liver transplantation
Table 1, continued.

the basis for classification of many of the metabolic disorders. The mitochondria in cells are organelles that play a major role in most metabolic pathways, and mitochondrial disorders are one of the most significant and common types of metabolic disorders. Defects in the storage and disposal of molecules also give rise to metabolic disorders.



Carbohydrates are used primarily as fuel and can be built and broken down rapidly. The major storage form is glycogen. They are also added to proteins to make glycoproteins. Fatty acids are long-chain molecules that are used to construct membranes. Fatty acids are derived from dietary fats. Excess fat is used as fuel by mitochondria. Proteins are made of amino acids.

Humans must eat eight kinds of amino acids and then convert these into twelve other types to make the twenty amino acids found in our proteins. Excess amino acids in the diet are used for fuel by mitochondria. Along the way, they generate organic acids. Nucleic acids—DNA and RNA—are the molecules that store and process genetic information. They must be built from smaller units, called nucleotides. The storage and interconversion of different types of nucleotides assures a steady supply.

Below, representative disorders of each system are discussed. Other disorders are listed in Table 1. Many of the disease names end in "emia." This suffix indicates a blood disorder, and the names are derived from the fact that most metabolic disorders are diagnosed by detecting abnormal levels of intermediates or other substances in the blood.

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 3Metabolic Disease - Enzymes Control Metabolic Reactions, Enzyme Defects Cause Metabolic Disorders, Approaches To Treatment, Major Classes Of Metabolic Disorders - Disorders of Amino Acid Metabolism, Disorders of Organic Acid Metabolism, Disorders of Fatty