What Is Schindler Disease?
Schindler disease was named after Detlev Schindler and Hiro Kanzaki. It is otherwise known as Alpha-N-Acetylgalactosaminidase deficiency, NAGA deficiency, or neuroaxonal dystrophy-Schindler type. It is a genetic lysosomal storage disorder that primarily causes neurological problems. Lysosomes are present in all cells, and they contain digestive enzymes, which help in the self-destruction of the cells if worn out. When there are low levels of inactivity of these enzymes, it can interfere with the cell's normal functions and cause the manifestations of the disease.
What Is the Etiology of Schindler Disease?
Schindler disease is an autosomal recessive disorder which means there are two copies of abnormal genes derived from each of the parents. The parents carry one abnormal gene each and do not show the clinical signs and symptoms. The mutation happens in the NAGA gene, which gives instructions for making the enzyme alpha-N-acetylgalactosaminidase. This enzyme helps the lysosomes to break down complexes called glycoproteins (sugar molecules attached to the proteins) and glycolipids (sugar molecules attached to fats). To be precise, this enzyme helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes. Finally, glycolipids and glycoproteins accumulate in the cells and cause the cells to malfunction and eventually die. Depending on the area of this cell damage, the signs and symptoms can be noted.
How Is Schindler Disease Classified?
Schindler's disease is classified into Type I, Type II, and Type III.
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Type I- It is the severe form of the disease in early childhood. It is also called infantile type and is associated with neurological symptoms. They have characteristic swellings at the end of nerve fibers. Eventually, they affect the proper nerve function by blocking the signals between the nerve cells.
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Type II- is a milder form of the disease with onset in adulthood.
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Type III is an intermediate form with onset and severity between the other two.
What Are the Signs and Symptoms of Schindler Disease?
The symptoms and severity of this disease can vary significantly in patients and families.
Type I Schindler disease-
The babies appear normal until 9 to 15 months. Then, they stop developing new skills which require mental and muscular coordination. They also begin losing abilities that they have already acquired. As the condition progresses, they develop blindness and seizures. They become unresponsive to external stimuli and do not survive past early childhood.
Type II Schindler disease-
It is also known as Kanzaki disease. It is a milder form of the condition in which the symptoms are not seen until the individual is in their second or third decade of life. The distinctive symptom of type II is the involvement of small blood vessels in the skin that cause small reddish lesions. They may be flat, raised, or appear in clusters and can occur anywhere in the body.
Angiokeratomas are due to an increase in the stratum corneum (a layer of skin) and manifest as minor marks of red to blue colors are seen. Lymphedema, swellings due to fluid accumulation in the tissue, can be seen in the legs. Neurological involvement can be there but not so severe as type I. The additional symptoms include hearing loss, ringing in the ears (tinnitus), muscle weakness, thick lips, a depressed nasal bridge, an enlarged nose tip, etc.
Type III Schindler disease-
It is intermediate in severity. The symptoms can vary between type I and type II.
How to Diagnose Schindler Disease?
Schindler disease can be diagnosed after birth through a thorough clinical examination, detailed patient history, and specialized tests.
They include,
Urine Tests- to look for complex compounds in the urine sample.
Enzyme Tests- showing reduced activity of the alpha-NAGA enzyme. This test is performed on white blood cells, blood plasma, or specific skin cells (fibroblasts) from affected individuals.
The biopsy of the rectum may show lysosomal accumulation in the nervous system.
Advanced Imaging Techniques like magnetic resonance imaging and computed tomography may reveal the degeneration of nerve cells.
In families with a previous history of Schindler disease, the disorder may be diagnosed before birth (prenatally) by tests such as amniocentesis and chorionic villus sampling (CVS).
A fluid sample surrounding the developing fetus during amniocentesis is removed and studied. In chorionic villus sampling, tissue samples are removed from a portion of the placenta. This can show that there is reduced activity of the alpha-NAGA enzyme.
What Are Other Conditions Similar to This Disease?
Symptoms of the following disorders can be very similar to those of Schindler disease.
This includes,
Infantile Neuroaxonal Dystrophy - It is a rare inherited disorder that affects the axons that signal messages from the brain to other parts of the body.
NBIA: Neurodegeneration with brain iron accumulation is a rare brain disease in which abnormal accumulation of iron in the brain and progressive degeneration of the nervous system.
Fabry Disease- It is is also an inherited disorder that results from the buildup of a particular type of fat in the body's cells.
What Are the Standard Therapies Available for Schindler Disease?
There is no specific treatment for individuals with Schindler disease. All the treatment measures are directed towards particular symptoms seen in each individual. They include maintaining adequate nutrition and hydration, managing infectious diseases, controlling seizures by antiepileptic drugs, controlling pain due to muscle spasms, etc. Many investigational therapies like enzyme replacement therapy, gene therapy, etc. Genetic counseling is given to affected families. It is a professional interaction between a healthcare provider and the affected family. The genetic counselor may estimate the chances that another relative may be affected.
Conclusion
The prognosis of this disease condition varies according to the type of NAGA deficiency. Type I has the worst diagnosis, and the other types have better outcomes. But the overall data on affected individuals is significantly less, and hence there is very little data about evidence-based life expectancy in these cases.
