Aspartylglycosaminuria is a very rare genetic disorder that is concentrated among persons of Finnish descent 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 the deficient activity of a particular enzyme, leading to the accumulation of metabolic products in the body.
Aspartylglucosaminuria is a condition that primarily affects mental functioning and movement. This condition worsens over time. Infants with aspartylglucosaminuria appear healthy at birth, and development is typically normal throughout early childhood. Around the age of 2 or 3, affected children usually begin to have delayed speech, mild intellectual disability, and problems coordinating movements. Other features that develop in childhood include respiratory infections, a protrusion of organs through gaps in muscles (hernia), and a growth spurt resulting in large head size (macrocephaly).
Causes
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 is 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 of 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.
Variants (also known as mutations) in the AGA gene cause aspartylglucosaminuria. The AGA gene provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complex chains of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). AGA gene variants result in a lack (deficiency) of the aspartylglucosaminidase enzyme in lysosomes, preventing the normal breakdown of glycoproteins. As a result, glycoproteins can build up within the lysosomes. Excess glycoproteins disrupt the normal functions of the cell and can result in cell death. A buildup of glycoproteins seems to particularly affect nerve cells in the brain; loss of these cells causes many of the signs and symptoms of aspartylglucosaminuria.
Treatment
Treatment of Aspartylglycosaminuria is symptomatic and supportive. Genetic counseling may be of benefit to families.
Research on inborn errors of metabolism is ongoing. Scientists are studying the causes of these disorders and trying to design enzyme replacement therapies that will return a missing enzyme to the body.
Preventions/interventions to signs and symptoms
Since ear infections and respiratory infections are common for children diagnosed with aspartylglucosaminuria, it is best to have regular checkups for both the ears and the respiratory tract.
Extreme sensitivity to the sun’s rays may develop; the best way to protect an individual diagnosed with aspartylglucosaminuria is to have them wear sunglasses, hats, or caps to protect their eyes. Epilepsy and insomnia can both be treated with medication.
It will be beneficial to children who are diagnosed with AGU to receive an education from a school with special teaching.[rx]
Habilitation
The process of habilitation for individuals diagnosed with AGU needs to be established in their early stages of life. The team for habilitation should include professionals who have experience in disabilities and the effects that having a disability can have on everyday life. Habilitation will include assessments, assistance with the choice of aids, and information concerning disabilities and counseling.[rx]
References
Asherson’s Syndrome
