What is Aspartylglucosaminuria?
Aspartylglucosaminuria or AGU for short, is an ultra-rare genetic disease belonging to a group of lysosomal storage disorders. Lysosomes are cellular compartments containing enzymes, responsible for the final (cellular) breakdown of fats, proteins and sugars. One of the lysosomal enzymes, called aspartylglucosaminidase (AGA), is necessary for breakdown of glycoproteins (proteins with a long-chain sugar attached to them). A malfunction of this enzyme leads to the physical and neurological disease manifestations.
Glycoproteins are very abundant and a necessary part of human life. Examples of glycoproteins present in a human body are antibodies (immunoglobulins), collagens (structural protein of connective tissue, transferrin (iron (Fe) transport in blood), hormones (like thyroid-stimulating hormone, alpha-fetoprotein, etc) and many others.
Aspartylglucosaminuria is an ultra-rare disorder, currently diagnosed in ~150 patients. Several nationalities, like Finnish and Turkish, have more cases. Nevertheless, patients with the disease have been diagnosed and are living in many countries of the world.
Early signs of Aspartylglucosaminuria (AGU):
All of the children with AGU have these three most common signs of the disease:
Articulation problems and speech/language delay
Clumsiness or delayed/slow motor functions
Recurring infections (ENT (ear, nose, throat) infections, slow healing scratches and cuts, etc.)
AGU child development
Pregnancy and infancy are normal. AGU babies have growth spurts in the first years of their lives, so they look very healthy. Once born, girls may have umbilical and boys inguinal hernias, which are usually repaired easily by surgeons. Infections are more common in AGU children compared to an average child and most AGU children get ear tubes due to continuous ear infections.
The first sign of AGU is slow speech development. The kids are more clumsy that their peers, with awkward walking or running, sometimes leaning forward. Delayed speech, attention deficit, clumsiness, restlessness, continuous respiratory infections are present in most of the preschoolers.
School age children learn material at a slower rate, and most of the AGU children attend special education by middle school. Some children learn how to read and write, participate in sports, art and crafts.
Children continue to develop until their twenties or later, depending on the level of care the child receives, and continue to learn. An AGU patient's life expectancy usually averages 30 -35 year of age for a male and 35-40 years of age for a female, with young adults typically dying from infection.
The disease was studied in Finland and most of the literature describes the progression of the disease in Finnish population. But cases of the disease have been reported in almost every country and affect many nations.
Autism or Aspartylglucosaminuria?
AGU initial symptoms are slow language development and speech delay which can be noticed as early as two years of age. School-age children are often diagnosed with ADHD or language/auditory processing disorder as they are slow to process information. Evaluators attribute that inattentiveness or inability to process information to one of these more common disorders. As a result, all AGU kids end up; being diagnosed with autism spectrum disorder and/or ADHD, and may be prescribed ADHD medications and other treatments.
However, the reason for the above presentation and behavior is a lack of cellular enzyme that breaks down glucoproteins. They are most abundant in the body tissues and in major organs, such as the liver, spleen, thyroid and brain. Unbroken pieces of glucoproteins accumulate in the body tissues and also excrete in urine. The process is gradual, damaging the tissues and organs, progressively destroying cells and leading to eventual death.
There is currently no approved treatment for AGU. ADHD or autism treatments will not help the child. The proper treatment for the disease is to introduce the missing enzyme back into the body. It is possible to do this with chaperone therapy or gene replacement therapy.
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