Homocystinuria: Clinical and pathological review of ten cases

Abstract

Homocystinuria is an inborn error on the pathway of the metabolism of methionine due to an absence of cystathionine synthetase in brain and liver. Clinical experience with ten cases occurring in seven families shows a consistent picture characterized by mental retardation, ectopia lentis, fine, fair hair, malar flush, thromboembolic and cardiovascular disease, skeletal deformities, and fatty change of liver. Family pedigrees suggest an autosomal recessive mode of inheritance. There are increased amounts of methionine and homocystine in the plasma and cerebrospinal fluid with increased excretion of homocystine in the urine. Fragmentation of the elastic tissue of large arteries is accompanied by a decrease in the glycoprotein and protein polysaccharide matrix. The fatty change of liver is due to a twofold increase in the neutral lipids. The brain shows focal necrosis and gliosis, and there are degenerative changes of the zonular fibers of the lens on light and electron microscopy. Homocystinuria is an inborn error on the pathway of the metabolism of methionine due to an absence of cystathionine synthetase in brain and liver. Clinical experience with ten cases occurring in seven families shows a consistent picture characterized by mental retardation, ectopia lentis, fine, fair hair, malar flush, thromboembolic and cardiovascular disease, skeletal deformities, and fatty change of liver. Family pedigrees suggest an autosomal recessive mode of inheritance. There are increased amounts of methionine and homocystine in the plasma and cerebrospinal fluid with increased excretion of homocystine in the urine. Fragmentation of the elastic tissue of large arteries is accompanied by a decrease in the glycoprotein and protein polysaccharide matrix. The fatty change of liver is due to a twofold increase in the neutral lipids. The brain shows focal necrosis and gliosis, and there are degenerative changes of the zonular fibers of the lens on light and electron microscopy.