About galb deficiency

What is galb deficiency?

Schindler disease is a rare inherited metabolic disorder characterized by the deficient activity of the lysosomal enzyme alpha-N-acetylgalactosaminidase (alpha-NAGA or alpha-galactosidase B). The enzyme defect leads to the abnormal accumulation of certain complex compounds (glycosphingolipids, glycoproteins, and oligosaccharides), which have terminal or preterminal N-acetylgalactosaminyl residues in many tissues of the body and in urine. Two major forms of Schindler disease exist - a severe form with onset in infancy (type I) and a milder form with onset in adulthood (type II). Some researchers have proposed a type III form of Schindler disease that is less severe than type I, but more severe than type II. The specific symptoms and severity of Schindler disease can vary from one person to another. Schindler disease is caused by mutations of the NAGA gene and is inherited as an autosomal recessive trait.

Schindler disease belongs to a group of diseases known as lysosomal storage disorders. Within cells, lysosomes are small compartments or organelles which are bound by membranes. They function as the primary digestive units of cells. Enzymes within lysosomes break down or digest particular nutrients and cellular debris. Low levels or inactivity of these enzymes leads to the abnormal accumulation of the substances that they normally breakdown, resulting in the enlargement and increased numbers of lysosomes within cells of the body, as well as leakage of their stored contents. These disturbances may interfere with normal cellular function and cause the disease manifestations.

What are the symptoms for galb deficiency?

Extreme pain during physical activity symptom was found in the galb deficiency condition

Some researchers have broken Schindler disease into three distinct types. Type I is a severe form that occurs during infancy and is associated with neurological symptoms. Type II is a milder form of the disorder with onset usually in adulthood and mild, if any associated neurological symptoms. Type III is an intermediate form whose onset and severity fall in between the other two. Consequently, the severity and specific symptoms of Schindler disease can vary greatly from patients in one family to those in another.

It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.


Schindler disease type I, the classic form of the disease, begins in infancy. Affected children develop normally until approximately 9 months to 1 year of age. They may then begin to exhibit a delay in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). After a period of such developmental delays, affected children may begin to lose previously acquired physical and mental abilities (developmental retrogression); such regression may begin at approximately 2 years of age. Affected children may then start to exhibit a variety of neurological symptoms, such as muscular Weakness and diminished muscle tone (hypotonia); involuntary Muscle spasms that result in slow, stiff movements (spasticity), misalignment of the eyes (strabismus); involuntary, rapid eye movements (nystagmus); and/or visual impairment due to the gradual deterioration of the nerves of the eyes (optic atrophy). They may also experience brief, shock-like Muscle spasms of the arms, legs, or entire body (myoclonic movements and grand-mal seizures).


In the adult-onset form of Schindler disease (also known as Schindler disease type II or Kanzaki disease), symptoms may not appear until the second or third decade of life. A distinctive symptom of Schindler disease type II is involvement of small blood vessels (telangiectasia) in the skin that cause reddish small skin lesions, and an increase of its horny layer (stratum corneum; hyperkeratosis) referred to as angiokeratomas. The dilation of small lymph vessels may lead to swelling (lymphedema) particularly of the lower extremities.

Angiokeratomas may first be restricted to a single area (localized), such as the lower torso, and then appear later in additional locations (e.g., from the lower torso to the chest area). These reddish Lesions may be flat or raised and vary in color, and may occur in clusters. Affected individuals may also have these Lesions in other areas of the body such as the mucous membranes including the mouth and eyes.

Individuals with Schindler disease type II have also mild intellectual impairment, but do not show the serious neurological complications associated with Schindler disease type I. Individuals with Schindler disease type II may also develop Distinctive facial features including mildly coarse features, thick lips, a depressed nasal bridge and an enlarged tip of the nose. Additional symptoms have been reported in the medical literature including vertigo, hearing loss, ringing in the ears (tinnitus), and muscle weakness. Patients may also experience Pain crises. Many of the latter manifestations are thought to be due to lysosomal storage.


Schindler disease type III, is an intermediate form the disorder. Symptoms can range from more serious intellectual impairment, neurological dysfunction and Seizures to milder neurological and psychiatric issues such as speech and language delays and mild autism-like symptoms.

What are the causes for galb deficiency?

Schindler disease is caused by mutations in the NAGA gene. These mutations are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of mutations for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits an abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

Investigators have determined that the NAGA (alpha-N-acetylgalactosaminidase) gene is located on the long arm (q) of chromosome 22 (22q13.2). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 22q13.2” refers to band 13 sub-band 2 on the long arm of chromosome 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Investigators have determined that the NAGA gene contains instructions for generating (encoding) an enzyme known as alpha-N-acetylgalactosaminidase (alpha-NAGA). All three forms of Schindler disease are characterized by very low levels or deficient activity of this enzyme. Low levels or absent activity of the enzyme leads to the abnormal accumulation of certain complex compounds (glycosphingolipids, glycoproteins, and oligosaccharides) in certain tissues of the body and in urine.

Although mutations in the NAGA gene are clearly linked to the accumulation of the complex compounds containing alpha-N-acetylgalactosaminyl residues in the body, some researchers have questioned whether mutations in the NAGA gene cause the neurological symptoms associated with Schindler disease. Although all individuals with Schindler disease have mutations in the NAGA gene, not all develop neurological symptoms. The severe neurological symptoms of type I Schindler disease are associated with characteristic swellings at the end of nerve fibers (axons). These swellings may be referred to as dystrophic axonal swellings or “spheroids”. The spheroids are characteristic of a neuroaxonal dystrophy – a severe alteration of nerve cells. These swellings appear to disrupt proper nerve function by blocking the transmission of impulses between nerve cells. Some researchers suspect that other factors in addition to or instead of mutations of the NAGA gene may cause the development of the neurological symptoms of Schindler disease. For example, some researchers have speculated that individuals with Schindler disease who have neurological symptoms may have additional mutations in an unrelated gene. However, no conclusive evidence exists to confirm this theory. More research is necessary to determine the exact complex mechanisms that ultimately cause the neuroaxonal dystrophy of Schindler disease.

What are the treatments for galb deficiency?

There is no specific therapy for individuals with Schindler disease. The treatment of Schindler disease is directed toward the specific symptoms that are apparent in each individual.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

What are the risk factors for galb deficiency?

Schindler disease affects males and females in equal numbers. The exact incidence of Schindler disease in the general population is unknown. Because cases of Schindler disease may go unrecognized or misdiagnosed, determining the disorder’s true frequency in the general population is difficult. As a group, lysosomal storage diseases are infrequent, although certain disorders may occur in specific ethnic or demographic groups at higher frequencies, about one in every 1,000-2,000 live births for Gaucher and Fabry diseases, or very infrequently (1 in 100,000 to 200,000 live births) for most of these disorders, which may be the case for alpha-N-acetylgalactosaminidase deficiency. Schindler disease was first reported in the medical literature in the late 1980s.

Is there a cure/medications for galb deficiency?

At birth, infants with galb deficiency appear healthy, but by 8 to 15 months, they stop growing and start losing their learned skills (developmental regression). Affected people experience seizures and blindness as the illness worsens, and gradually they lose consciousness of their surroundings and become slow to react. Most people who have this type of illness do not live into early childhood.

Children with the condition may show early warning signs and symptoms such as developmental disability, seizures, a weakened and expanded heart (cardiomyopathy), and an expanded liver (hepatomegaly)

In certain instances, those who have this type of disorder show behavioral issues starting in early childhood along with other characteristics of autism spectrum disorders. Communication and socialization abilities that are compromised are hallmarks of autism spectrum disorders.

Cure or Medication for galb deficiency

Galb deficiency has no known cure. Painkillers and gastrointestinal medications can help with symptoms. In order to prevent heart difficulties, renal disease, and other potentially fatal effects, there are two treatments that could slow down the accumulation of fatty substances:

1. Replacement of enzymes therapy: You get an intravenous (IV) infusion of synthetic agalsidase beta enzyme every two weeks. This substitute enzyme fills up for the absent alpha-GAL enzyme, preventing the buildup of fatty compounds. To avoid an allergic reaction, you could receive an antihistamine as well as other drugs before therapy.

2. Therapy with oral chaperones: Chaperones are tiny molecules that fix damaged alpha-GAL enzymes. The fatty material can subsequently be broken down by the repaired enzymes. To stabilize the dysfunctional alpha-GAL enzyme with this medication, you take a pill every other day. This medicine cannot be used to treat all Fabry disease patients. Whether you qualify for this treatment depends on the precise genetic mutation in the GLA gene that you have.

Burning, tingling or painful sensations in the hands or feet,Extreme pain during physical activity,Inability to tolerate heat or cold,Defect in the eye, loss of vision, and hearing loss,Dizziness, fatigue, and fever,Gastrointestinal problems
Heart problems,Nerve damage,Kidney failure,Stroke
Painkillers,Antihistamines,Enzyme replacement therapy

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