A-N-Acetylgalactosaminidase Deficiency – Causes, Symptoms & Treatment

A-N-acetylgalactosaminidase deficiency

A-N-acetylgalactosaminidase deficiency is a lysosomal storage disease that occurs only very rarely. It is divided into a juvenile and an adult form.

What is a-N-acetylgalactosaminidase deficiency?

A-N-acetylgalactosaminidase deficiency or alpha-N-acetylgalactosaminidase deficiency is also referred to in medicine as Schindler’s disease, Schindler’s disease or Kanzaki’s disease. This refers to an extremely rare lysosomal storage disease, the inheritance of which is autosomal recessive. Physicians distinguish between a juvenile form, which occurs in children and adolescents, and an adult form, from which adult people suffer.

The juvenile form of alpha-N-acetylgalactosaminidase deficiency is called Schindler’s disease, while the adult form is called Kanzaki’s disease. However, there are also subdivisions into Schindler’s disease type I for the juvenile form and Schindler’s disease type II for the adult form. Also possible is a mixture of both forms, which is called Schindler’s disease type III.

All three forms of the disease belong to the oligosaccharidoses (glycoproteinoses), which include fucosidosis and sialic acid storage disease. The term Schindler’s disease or Schindler’s disease for alpha-N-acetylgalactosaminidase deficiency goes back to the German geneticist Detlev Schindler.

He was the first to describe the disease in 1988. A year later, the adult form was described by the Japanese physician T. Kanzaki. He discovered in 1991 that an alpha-N-acetylgalactosaminidase deficiency was the cause of the disease.


The a-N-acetylgalactosaminidase deficiency is caused by a reduced activity of the enzyme alpha-N-acetylgalactosaminidase. Responsible for the enzyme defect are missense or nonsense mutations on the NAGA gene, which encodes alpha-N-acetylgalactosaminidase.

The NAGA gene is located on chromosome 22 gene locus q11. The enzyme alpha-N-acetylgalactosaminidase has the task of catalyzing the cleavage of N-acetylgalactosaminisamine from different glycolipids and glycoproteins. The genetic defect causes a reduced activity of the enzyme, so that substances accumulate in the body cells that are not metabolized.

In most cases, these are proteoglycans, glycosphingolipids and N- or O-linked glycoproteins. Their accumulation causes damage to the cell and the affected organs. Alpha-N-acetylgalactosaminidase deficiency occurs so rarely that there is no precise information on its frequency.

Around the world, only twelve patients from eight families are known to have suffered from Schindler’s disease. Not every patient develops neurological complaints. For the occurrence of neurological symptoms, some physicians suspect the influence of additional factors. However, there is still no evidence for this assumption.

Symptoms, complaints & signs

The symptoms of alpha-N-acetylgalactosaminidase deficiency depend on the form of the disease. In the context of Schindler’s disease type I, progressive hypotonia occurs in the first year of life. In addition, the affected babies suffer from a pronounced psychomotor regression.

Movement disorders, spastic quadriplegia and myoclonic cerebral seizures were also recorded as manifestations. In addition, there is a risk of blindness of the child. If there is an adult form of alpha-N-acetylgalactosaminidase deficiency, i.e. Schindler’s disease type 2, symptoms similar to Fabry disease occur.

Thus, in the patients there are angiokeratomas, which are benign skin lesions. Many patients are mentally retarded to a minor extent. An intermediate clinical form is Schindler’s disease type III. Those affected suffer from neurological malfunctions, cerebral seizures and mental disabilities.

However, less severe forms are also possible, which are accompanied by mild psychiatric and neurological complaints, delayed speech development or autism-like symptoms.

Diagnosis & course

The diagnosis of alpha-N-acetylgalactosaminidase deficiency is possible by demonstrating reduced NAGA activity. For this purpose, enzyme tests are carried out in blood plasma, leukocytes or cultured fibroblasts or lymphoblasts. Likewise, the chromatographic detection of oligosaccharides within the urine allows the diagnosis of enzyme deficiency.

Furthermore, a DNA analysis can be performed, but this is not necessary in most cases. During pregnancy, prenatal diagnosis of enzyme deficiency can also be performed by mutation analysis of the NAGA gene following chorionic villus sampling or amniocentesis. However, the respective form of disease cannot be determined.

The differential diagnosis of Fabry syndrome, panthothenate kinase-associated neurodegeneration and infantile neuroaxonal dystrophy, which also have enzyme defects, is also important. The course of alpha-N-acetylgalactosaminidase deficiency depends on the respective form of the disease.

For example, Schindler’s disease type I is considered unfavorable, while the prognosis for the other two types is more favorable. However, the number of sick people is so low that no meaningful statements can be made about life expectancy.


The symptoms and complications of A-N-acetylgalactosaminidase deficiency strongly depend on its form. In most cases, however, there are movement disorders, so that those affected are relatively restricted in their everyday lives. There are also cramps associated with severe pain.

Especially babies suffer from a strong disorder of development, as a result of which spasticity can develop in the child. In some cases, A-N-acetylgalactosaminidase deficiency leads to complete blindness of the patient. The regression of intelligence leads to retardation and thus also to sown disabilities.

These usually significantly restrict the patient’s everyday life and have a negative effect on the quality of life. Often those affected are dependent on the help of other people. Retardation can also lead to a word-finding disorder or a speech disorder. It is not possible to treat A-N-acetylgalactosaminidase deficiency causally.

For this reason, the person concerned must take antibiotics. Likewise, certain complications must be avoided directly. These include, for example, pneumonia. Furthermore, the patient may also be dependent on artificial feeding.

When to go to the doctor?

In the case of A-N-acetylgalactosaminidase deficiency, medical treatment must be given in any case. This deficiency does not go away on its own and there is no spontaneous cure of this disease. In any case, a doctor must be consulted if the parents notice a regression of motor and mental abilities in their child or baby. Even complaints from simple movements or sequences can indicate the A-N-acetylgalactosaminidase deficiency and should be examined by a doctor.

Furthermore, various spasticities are also a sign of a disease. Not infrequently, patients also suffer from mental retardation and other malfunctions. If these complaints are present, treatment is necessary in any case. If no treatment occurs, this can lead to considerable discomfort and complications in adulthood and thus significantly reduce the quality of life of the person concerned.

Severely delayed speech development can also be a sign of A-N-acetylgalactosaminidase deficiency and must therefore be investigated. As a rule, a general practitioner can be consulted to determine A-N-acetylgalactosaminidase deficiency. The further treatment of the individual complaints is then carried out by a specialist.

Treatment & Therapy

A causal therapy of alpha-N-acetylgalactosaminidase deficiency is not feasible. Therefore, the medical procedure is limited to the treatment of the symptoms. These include a sensible diet and hydration, the prevention of infectious diseases, which can also be done by the administration of , as well as the containment of cerebral seizures by the administration of antiepileptic drugs.

Other treatment steps include physiotherapy measures to prevent pneumonia and contractures and reduce pain or spasticity with the help of medication. Furthermore, aspiration prophylaxis can take place through artificial feeding.

Recent studies have shown that a-N-acetylgalactosaminidase deficiency is a protein folding disorder, so enzyme replacement therapy is being discussed as a useful treatment measure. Another conceivable therapeutic approach for the treatment of lysosomal storage disorders is gene therapy. Because Schindler’s disease is inherited as an autosomal recessive trait, genetic counseling of affected families is recommended.

Outlook & Forecast

The A-N-acetylgalactosaminidase deficiency can lead to various complaints. In most cases, however, the deficiency leads to delayed psychomotor development. Often the patient is dependent on the help of other people in adulthood and can not master everyday life alone. Movement disorders also occur. These can be noticeable by a limp or by disturbances in coordination.

In the worst case, the patient can also go blind or suffer from severe visual disturbances due to the A-N-acetylgalactosaminidase deficiency. Not infrequently, mental disabilities occur, which greatly reduce the quality of life of the person concerned. Likewise, speech disorders and word-finding disorders occur, which can affect life. Especially children are affected by the complaints of A-N-acetylgalactosaminidase deficiency of bullying and teasing.

Causal treatment of A-N-acetylgalactosaminidase deficiency is not possible, so treatment is primarily aimed at reducing symptoms. Various therapeutic measures can be used to reduce the disorders of development. In many cases, however, the patient is dependent on outside help in everyday life. Life expectancy is not affected by the deficiency.


Meaningful preventive measures against alpha-N-acetylgalactosaminidase deficiency are not known. Schindler’s disease is one of the extremely rare diseases.


Since A-N-acetylgalactosaminidase deficiency is a congenital disease that cannot be treated causally, but only purely symptomatically, complete treatment is not possible. The person concerned is dependent on lifelong treatment, which is why the possibilities of aftercare are very limited.

As a rule, the patient is often dependent on the intake of medication and antibiotics due to the A-N-acetylgalactosaminidase deficiency. Possible interactions with other medications should be taken into account, whereby antibiotics must not be taken together with alcohol. In case of a seizure, the hospital should be visited or the emergency doctor should be called directly.

Furthermore, the lungs should be spared to avoid inflammation. Therefore, in case of A-N-acetylgalactosaminidase deficiency, the patient should not smoke in any case. A healthy diet and a general healthy lifestyle have a very positive effect on the course of the disease.

If the patient has a desire to have children, genetic counseling makes sense to prevent the disease from being passed on to the children. Since patients often suffer from movement restrictions, physiotherapy is useful to alleviate them. Many exercises can also be done in your own home.

What you can do yourself

An existing A-N-acetylgalactosaminidase deficiency is an incurable disease. Therefore, medical treatment is indispensable. Self-treatment measures can only be based on the symptoms to make everyday life easier. It is important to observe the child closely by the parents.

Parents can best help their child through understanding and patience, love and care. Furthermore, therapy and speech therapy treatments are always based on a dual concept: on-site therapy with the specialist and the execution of the exercises at home. Here, parents should be active consistently and with patience. Pay attention to a rich in vitamins and minerals, regular exercise and plenty of fresh air. This strengthens the immune system and reduces the risk of infection. In the case of a tendency to spasm, the affected person should not be alone for a long time and should be checked whether he can injure himself in an onset of seizure.

In most cases, patients cannot cope with everyday life themselves and require constant care. If parents cannot afford this – especially with older children and adults – they should not be afraid to seek help. This can take the form of a caregiver or placement in an adequate facility. If there is a further desire to have children, a consultation with a specialist is recommended, as the disease is inherited.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.