Schindler disease

α -N- acetylgalactosaminidase deficiency is a extremely rare autosomal recessive lysosomal storage disease. In the juvenile form, the disease as Crohn's Schindler and referred to in the adult form as Kanzaki disease. In some publications, the juvenile form is also known as Crohn's Schindler Type I and the adult form as Schindler disease type II. An intermediate mixture of both diseases is called Schindler disease type III. All three diseases are attributed to the oligosaccharidoses.

Aetiology and prevalence

In the patients affected by the Schindler 's disease, the enzyme α -N- acetylgalactosaminidase is reduced in its activity. Cause of the enzyme defect is nonsense or missense mutations in the α -N- acetylgalactosaminidase coding gene ( NAGA ) gene, which is located on chromosome 22 q11 locus. The enzyme catalyzes the cleavage of N - acetylgalactosamine of various glycoproteins and glycolipids. The genetic defect caused by the reduction in the enzyme activity leads to an accumulation of non- metabolized substances in the cells. This is mainly to N- or O- linked glycoproteins, proteoglycans and glycosphingolipids, the α -N- acetylgalactosamine - groups terminally bonded. This buildup can cause damage in the cell and the institutions concerned.

The α -N- acetylgalactosaminidase deficiency is an extremely rare disease, its exact prevalence is unknown. Around twelve patients have been reported worldwide from eight families.

Symptoms and diagnosis

In Crohn's Schindler Type I disease is characterized by a progressive hypotonia in the first year of life. In addition, disturbances in movement ( extrapyramidal syndrome ), a rapid psychomotor regression, myoclonic seizures, spastic quadriplegia and blindness. In the adult form one of the Fabry -like symptoms is observed. Sufferers have angiokeratoma and only a slight mental retardation. The intermediate form ( Schindler disease type III) is manifested by behavioral disturbances, seizures, and psychomotor retardation.

The α -N- acetylgalactosaminidase deficiency can be diagnosed by the chromatographic detection of the oligosaccharides in the urine. In the laboratory, also, the activity of α -N- acetylgalactosaminidase in leukocytes, fibroblasts or trophoblastic tissue can be determined. DNA analysis is possible, but usually not necessary.

Therapy

There is currently no specific treatment for Wolman 's disease. Treatment is symptomatic.

First description

The α -N- acetylgalactosaminidase deficiency was first described in 1988 by the Würzburg geneticist Detlev Schindler. He is the namesake for the Crohn's Schindler. T. Kanzaki - eponym for the disease Kanzaki - 1989 first described the symptoms of the adult form of the α -N- galactosaminidase deficiency in a 46 -year-old Japanese woman. Two years later he recognized as the cause of the α -N- galactosaminidase deficiency.