Schindler disease

Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency, is a rare disease found in humans. This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase), attributable to mutations in the NAGA gene on chromosome 22,^[1][2] which leads to excessive lysosomal accumulation of glycoproteins.^[3] A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.

Schindler disease
Other names	NAGA deficiency
Schindler disease is inherited via an autosomal recessive manner
Specialty	Endocrinology

Types

There are three main types of the disease each with its own distinctive symptoms.^[4]

Type I: infantile form, infants will develop normally until about a year old. At this time, the affected infant will begin to lose previously acquired skills involving the coordination of physical and mental behaviors. Additional neurological and neuromuscular symptoms such as diminished muscle tone, weakness, involuntary rapid eye movements, vision loss, and seizures may become present. With time, the symptoms worsen and children affected with this disorder will experience a decreased ability to move certain muscles due to muscle rigidity. The ability to respond to external stimuli will also decrease. Other symptoms include neuroaxonal dystrophy from birth, discoloration of skin, and telangiectasia or widening of blood vessels.

Type II: adult form, symptoms are milder and may not appear until the individual is in his or her 30s. Angiokeratomas, an increased coarsening of facial features, and mild intellectual impairment are likely symptoms.

Type III: is considered an intermediate disorder. Symptoms vary and can include to be more severe with seizures and intellectual disability, or less severe with delayed speech, a mild autistic-like presentation, and/or behavioral problems.

Cause

Diagnosis

Amniocentesis or chorionic villus sampling can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies can be used to diagnose Schindler disease. Genetic testing is also always an option, since different forms of Schindler disease have been mapped to the same gene on chromosome 22;^[2] though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.^[5] The Genetic Testing Registry can be used to acquire information about the genetics tests for this condition.^[6]

Management

Infants with Schindler disease tend to die within four years of birth; therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.^{[citation needed]}

History

Schindler disease was named after Detlev Schindler (born 1946) M.D., the first author of a 1988 paper detailing the disease. It is also named after the Japanese biochemist and physician, Hiro Kanzaki (born 1949), who further studied it and released papers detailing the disease in 2006.^{[citation needed]}

See also

• List of cutaneous conditions

References

1. Wang AM, Schindler D, Desnick R (November 1990). "Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy". J. Clin. Invest. 86 (5): 1752–6. doi:10.1172/JCI114901. PMC 296929. PMID 2243144.
2. Online Mendelian Inheritance in Man (OMIM): 609241
3. Cantz M, Ulrich-Bott B (1990). "Disorders of glycoprotein degradation". J. Inherit. Metab. Dis. 13 (4): 523–37. doi:10.1007/BF01799510. PMID 2122119. S2CID 21567863.
4. "Schindler disease". International Advocate for Glycoprotein Storage Diseases. (International Society for Mannosidosis & Related Diseases, ISMRD). Retrieved 2008-11-13.
5. "Schindler Disease". National Organization for Rare Disorders (NORD). Retrieved 2008-11-13.
6. "Kanzaki disease". Genetic and rare diseases information center. Retrieved 17 April 2018.

Further reading

• Reference, Genetics Home. "Schindler disease". Genetics Home Reference. Retrieved 27 December 2016.

External links