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HomeHealth articlesaspartylglucosaminuriaAspartylglucosaminuria - Causes | Diagnosis | Signs | Symptoms

Aspartylglucosaminuria - Causes, Diagnosis, Signs and Symptoms

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Aspartylglucosaminuria is an inherited disorder characterized by decreased mental functioning and other health complications.

Medically reviewed by

Dr. Pandian. P

Published At April 1, 2022
Reviewed AtMay 30, 2024

Introduction:

The first incidence of aspartylglucosaminuria (AGU) was reported by Jenner and Pollit in 1967 in their patients who had mental retardation. It is a genetic condition, meaning a person is born with it. Decreasing mental functions is the characteristic feature of this disease, and the affected child usually seems to have normal mental function in the initial years with a progressive decline in mental functions. This condition is also known by the terms aspartylglycosaminuria, AGA deficiency, glycosylasparaginase deficiency, and aspartylglucosaminidase deficiency.

What Is Aspartylglucosaminuria?

As the name indicates, aspartylglucosaminuria occurs due to a defect in the aspartylglucosaminidase enzyme. It is an autosomal recessive disorder, meaning the child must inherit one copy of the defective AGA gene from both father and mother. The parents of such children are known as carriers as they carry one copy of the mutated AGA gene and remain asymptomatic, as well as pass it on to their children. It is a lysosomal storage disease. Most people with this disease survive until their mid-adulthood.

What Are the Signs and Symptoms of People With Aspartylglucosaminuria?

Children born with AGU tend to appear healthy at birth, with normal mental functions and development throughout childhood. They grow taller than their healthy counterparts. However, as they reach the pubertal age, a lack of the pubertal growth spurt arrests their growth, resulting in short stature in adulthood.

  • Delayed Speech - Around two to three years of age, the affected child begins to show the first sign of the disease, that is, delayed speech. Usually, healthy children start to speak around the age of one year. But in this condition, even at the age of two or three, children do not speak clearly.

  • Intellectual Disability - The affected child has difficulties in learning or exhibits slow-pace learning. The intellectual disability worsens during adolescence.

  • Seizures - Affected adults have problems with movements and experience seizures.

  • Unlearn - Whatever speech skills they had learned during childhood, they forget them. They hardly remember words to speak. The learned motor skills also deteriorate, and as a result, they limit their ability to use their limbs and become dependent on others.

  • Weak Bones - They develop osteoporosis in their adulthood, wherein bones become weak and brittle with increased susceptibility to fractures.

  • Joint Hypermobility - Affected people’s joints become unusually and excessively flexible beyond their normal range of motion without any pain. They also have loose skin.

  • Respiratory Tract Infections - The affected children develop frequent upper respiratory tract infections.

  • Changes in Facial Appearance - The affected individuals have typical facial features such as hypertelorism (more than normal space between the eyes), small ears and nose (broadened), full lips, and a squarish face.

Apart from these features, they also have the following;

  • Short neck.

  • Scoliosis.

  • Behavior problems.

  • Cataracts.

  • Mental retardation.

These are the range of signs and symptoms an AGU-affected individual may experience. Not all people with AGU experience all the signs and symptoms mentioned above.

What Causes Aspartylglucosaminuria?

Lysosomes are recycling centers present in the cells. They contain enzymes like aspartylglucosaminidase that help break down glycoproteins. The AGA gene provides instructions for the production of the enzyme aspartylglucosaminidase.

In the case of mutation of the AGA gene, there is a deficiency of aspartylglucosaminidase due to which the glycoproteins are not efficiently broken down. This leads to excessive accumulation of the glycoprotein in the cells and tissues and its increased excretion in the urine.

This excessive build-up of glycoproteins disrupts normal cell functions, especially of the nerve cells in the brain. Major signs and symptoms of the disease are due to the ill effects of increased glycoprotein levels in the brain cells.

How Prevalent Is Aspartylglucosaminuria?

This is a very rare genetic condition. Though it can affect people of any race, it has a predominance among Finnish people. Nearly 1 in 18,500 people are affected exclusively in Finland.

How Is Aspartylglucosaminuria Diagnosed?

Apart from the presenting clinical features of the disease, the doctor would suggest a urine test.

  • Urine Examination - An amino acid or oligosaccharide chromatography testing of the urine of the affected person reveals 1000-fold elevated levels of aspartylglucosamine (the metabolite accumulating in body fluids).

  • In cultured skin fibroblasts, lymphocytes, and amniocytes, there is a deficiency of the enzyme aspartylglucosaminidase. Its levels are also deficient in plasma and seminal fluid.

What Are the Other Disorders With Similar Symptoms as Aspartylglucosaminuria?

Several other disorders may present with similar symptoms to AGU, making differential diagnosis challenging. Some disorders with overlapping symptoms are:

  • Pseudo-Hurler Polydystrophy -This is a rare inherited disorder that affects children. It causes joint stiffness, short stature, facial changes, and sometimes problems with the heart valve. Mental development might also be affected, but it is usually mild.

  • Mucopolysaccharidoses (MPS) - These are genetic diseases where the body cannot break down certain sugars properly. This leads to a build-up of these substances in various tissues, causing problems with growth, mental development, and physical features like joint stiffness and facial changes. Symptoms usually start to show around age one and get worse over time.

  • I-Cell Disease - This starts showing symptoms very early in life, even as early as six months old. Children with this condition might have coarse facial features, excessive hair growth, and skeletal abnormalities. Mental and physical development is often delayed.

Can Aspartylglucosaminuria Be Cured?

Unfortunately, there is no treatment option available that can prevent, slow down the progression, or cure the disease permanently as of now. However, allogeneic bone marrow grafting has been found to be beneficial. Bone marrow transplantation needs to be performed during infancy to obtain promising results.

Symptomatic Management:

Though it is not curable, the symptoms of the disease can be managed with symptom-based treatment and rehabilitation.

  • Affected children need to gain education and training from schools with special teaching.

  • Medications to treat seizures are also available.

  • Since they are prone to respiratory tract infections, regular consultation with the physician and preventive measures such as wearing masks when outside, drinking warm water, etc., need to be followed.

  • Since they have weak bones and are susceptible to fractures, care must be taken to avoid falling on the ground or getting hit.

Conclusion:

Several autosomal recessive diseases, including aspartylglucosaminuria, can affect future children if both spouses carry a copy of the mutated gene. Undergoing premarital genetic screening tests and counseling can help prevent the chances of passing a health condition to children. If there are doubts about the possibility of passing a mutated gene to a future child, consulting experts is just one click away.

Dr. Pandian. P
Dr. Pandian. P

General Surgery

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