Inborn errors of metabolism featuring enzyme deficiencies can importantly compromise the skeleton. Hypophosphatasia (HPP) is the rare heritable rickets or osteomalacia characterized biochemically by subnormal activity of the tissue-nonspecific (bone/liver) isoenzyme of alkaline phosphatase. HPP disturbs mainly the skeleton and teeth but with the greatest range of severity of all skeletal diseases. Mucopolysaccharidoses are caused by diminished activity of the lysosomal enzymes that degrade glycosaminoglycans. Homocystinuria is a rare autosomal recessive disorder caused by cystathionine Β-synthase deficiency. Consequently, homocystine, an intermediate in methionine metabolism, accumulates endogenously. This can cause thrombosis and embolism and modification of connective tissue proteins including fibrillin within periosteum and perichondrium. Alkaptonuria is an autosomal recessive disorder caused by a deficiency of homogentisic acid oxidase due to loss of function mutations within the AKU gene. Wilson disease and Menkes disease are genetic disorders of copper metabolism caused by deficiencies of copper.
- Enzyme deficiency
- Wilson disease