Schindler disease
Encyclopedia
Schindler disease, also known as Kanzaki disease and Alpha-N-acetylgalactosaminidase deficiency is a rare congenital
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...

 metabolic disorder 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
NAGA (gene)
Alpha-N-acetylgalactosaminidase is an enzyme that in humans is encoded by the NAGA gene.-Further reading:...

 on chromosome 22, which leads to excessive lysosomal accumulation
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...

 of glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

s. A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids
Glycosphingolipids
Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They include:* Cerebrosides* Gangliosides* Globosides...

 throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

 disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.

There are three main types of the disease each with its own distinctive symptoms.

In the 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
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or 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 symptms include neuroaxonal dystrophy from birth
Infantile neuroaxonal dystrophy
Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in...

, discoloration of skin, Telangiectasia
Telangiectasia
Telangiectasias /tɛ.læn.dʒiː'ɛk.teɪ.ʃi:ə/ are small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. They can develop anywhere on the body but are commonly seen on the face around the nose, cheeks, and chin...

 or widening of blood vessels.

In 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 mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...

, or less severe with delayed speech, a mild autistic like presentation, and/or behavioral problems.

Infants with Schindler disease tend to die within 4 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.

Amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...

 or chorionic villus sampling
Chorionic villus sampling
Chorionic villus sampling , sometimes misspelled "chorionic villous sampling", is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it...

 can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies
Skin biopsy
Skin biopsy is a biopsy technique in which a skin lesion is removed and sent to the pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days. It is commonly performed by dermatologists. Skin...

 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; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.

Schindler disease was named after Detlev Schindler M.D., the first author of a 1988 paper detailing the disease.

External links

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