Schindler disease

Other names:alpha-galactosidase B deficiency;alpha-galNAc deficiency, Schindler type;alpha-N-acetylgalactosaminidase deficiency;alpha-NAGA deficiency;angiokeratoma corporis diffusum-glycopeptiduria;GALB deficiency Kanzaki disease;lysosomal glycoaminoacid storage disease-angiokeratoma corporis diffusum;NAGA deficiency;neuroaxonal dystrophy, Schindler type;neuronal axonal dystrophy, Schindler type

Schindler disease is an inherited disorder that primarily causes neurological problems.

Types

There are three types of Schindler disease. Schindler disease type I, also called the infantile type, is the most severe form. Schindler disease type II, also called Kanzaki disease, is a milder form of the disorder that usually appears in adulthood. Schindler disease type III is intermediate in severity between types I and II.

Epidemiology

Schindler disease is very rare. Only a few individuals with each type of the disorder have been identified.

Cause

Mutations in the NAGA gene cause Schindler disease. The NAGA gene provides instructions for making the enzyme alpha-N-acetylgalactosaminidase. This enzyme works in the lysosomes, which are compartments within cells that digest and recycle materials. Within lysosomes, the enzyme helps break down complexes called glycoproteins and glycolipids, which consist of sugar molecules attached to certain proteins and fats. Specifically, alpha-N-acetylgalactosaminidase helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes.

Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycolipids. These substances accumulate in the lysosomes and cause cells to malfunction and eventually die. Cell damage in the nervous system and other tissues and organs of the body leads to the signs and symptoms of Schindler disease.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Babies with Schindler disease type I appear healthy at birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired (developmental regression). As the disorder progresses, affected individuals develop blindness and seizures, and eventually they lose awareness of their surroundings and become unresponsive. People with this form of the disorder usually do not survive past early childhood.

Schindler disease type II affected individuals may develop mild cognitive impairment and hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). They may experience weakness and loss of sensation due to problems with the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). Clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) are characteristic of this form of the disorder.

Schindler disease type III affected individuals may exhibit signs and symptoms beginning in infancy, including developmental delay, seizures, a weakened and enlarged heart (cardiomyopathy), and an enlarged liver (hepatomegaly). In other cases, people with this form of the disorder exhibit behavioral problems beginning in early childhood, with some features of autism spectrum disorders. Autism spectrum disorders are characterized by impaired communication and socialization skills.

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; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease. The Genetic testing Registry can be use to acquire information about the genetics tests for this condition.

Treatment

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.

Classification	ICD-10: E77.1 OMIM: 609241 Online Mendelian Inheritance in Man (OMIM) 609242 DiseasesDB: 30058
External resources	Orphanet: 3137

Schindler disease Resources
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NIH genetic and rare disease info

• NIH info on Schindler disease

Schindler disease is a rare disease.