About glycosylasparaginase deficiency

What is glycosylasparaginase deficiency?

Aspartylglycosaminuria is a very rare genetic disorder that is concentrated among persons of Finnish decent, but is also found, even more rarely, in other populations around the world. It is an inborn error of metabolism, and one of the lysosomal storage diseases. It becomes apparent after the infant is a few months old. Major symptoms may include coarse facial features, spine and eye deformities, behavior problems and mental retardation. Aspartylglycosaminuria occurs as a result of deficient activity of a particular enzyme, leading to the accumulation of metabolic products in the body.

What are the symptoms for glycosylasparaginase deficiency?

Scoliosis symptom was found in the glycosylasparaginase deficiency condition

Aspartylglycosaminuria is a lysosomal storage disease characterized by normal development during the first months of life after which abnormal development begins to occur. Diarrhea and infections that keep reoccurring are noticed. After the first few years facial features begin to get coarse which continues during the following years. The skeleton may become deformed and the ocular lens may develop crystalline deposits. Mental deterioration may begin to occur after age five and behavior problems are common. Lung, heart and blood problems tend to occur in later years. The patient may show mental retardation uneven development of the head and face with sagging cheeks, a wide nose and broad face. The spine may be twisted (scoliosis) and the neck may be unusually short. Adult stature is usually below normal.

What are the causes for glycosylasparaginase deficiency?

Aspartylglycosaminuria is a lysosomal storage disease. Lysosomes are cell particles containing enzymes that break down large molecules. A deficiency of the lysosomal enzyme, aspartylglycosamidase, causes the accumulation of a substance known as aspartylglucosamine in the body, resulting in disorders in the various body systems.

This disorder is inherited as an autosomal recessive trait. The gene responsible for this disorder is located on the long arm of the fourth chromosome at 4q32-q33. Those affected by this disorder are most often of Finnish ancestry. However, aspartylglycosaminuria can occur in people of all heritages.

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 subdivided into many bands that are numbered. For example, “chromosome 4q32-q33” refers to a region between bands 32 and 33 on the long arm of chromosome 4. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same 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% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% 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%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

What are the treatments for glycosylasparaginase deficiency?

Treatment of Aspartylglycosaminuria is symptomatic and supportive. Genetic counseling may be of benefit for families.

What are the risk factors for glycosylasparaginase deficiency?

Glycosylasparaginase deficiency/Aspartylglucosaminuria (AGU) is an inherited disease that causes mental functioning, accompanied by an increase in skin, bone, and joint issues.

The condition doesn't show any symptom at birth. However, the signs and symptoms may become apparent between two and four years of age and become progressively worse as the individual ages.

Certain risk factors for developing this condition include,

  • Glycosylasparaginase deficiency is an autosomal recessive genetic condition inherited from both parents.
  • People with this condition are born with two copies of the mutated AGA gene.
  • One copy comes from his/her mother, and the other copy comes from the father.
  • If the individual inherits changes in both of his AGU genes (autonomic recessive inheritance).
  • When a person receives one changed form of the gene AGU from one of the parents, the individual is then classified as a carrier.

Mental deterioration,Scoliosis,Lungs and heart problem
Diarrhea,Infections,The coarseness of facial features begins, and continues for several years,Bones may become deformed

Is there a cure/medications for glycosylasparaginase deficiency?

Aspartylglucosaminuria also known as Glycosylasparaginase deficiency is a disorder that predominantly affects mental and physical functioning. This condition deteriorates over time.

  • Newborns with aspartylglucosaminuria appear normal at birth and develop normally throughout childhood.
  • Around the age of two or three, affected children typically exhibit deferred speech, gentle intellectual disability, and difficulties coordinating movements.
  • Other characteristics that emerge in early life include respiratory infections, organ protrusion through muscle gaps (hernia), and a growth spurt that results in a massive head size (macrocephaly).
  • In adolescence, cognitive impairment and movement problems worsen. Most individuals with this condition lose a significant portion of their learned speech, and affected adults typically have only a few phrases in their vocabulary.
  • Adults with aspartylglucosaminuria frequently have psychological problems and may experience seizures.
  • Glycosylasparaginase deficiency treatment
  • Traditional Therapies
  • Aspartylglycosaminuria is treated symptomatically and supportively. Families may benefit from genetic counselling.
  • Experimental Therapies
  • The study of inborn metabolic errors is ongoing. Scientists are researching the causes of such disorders and developing enzyme replacement therapies to replace missing enzymes in the body.

Mental deterioration,Scoliosis,Lungs and heart problem
Diarrhea,Infections,The coarseness of facial features begins, and continues for several years,Bones may become deformed

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