Aspartylglucosaminuria | |
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Classification and external resources | |
Aspartylglucosamine |
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ICD-10 | E77.1 |
OMIM | 208400 |
DiseasesDB | 952 |
Aspartylglucosaminuria (AGU), also called aspartylglycosaminuria, is a rare, autosomal recessive[1] lysosomal storage disorder caused by deficient activity of the enzyme N-aspartyl-beta-glucosaminidase (aspartylglucosaminidase). This enzyme normally cleaves long sugar chains known as oligosaccharides in the lysosome. When N-aspartyl-beta-glucosaminidase is deficient these long sugar chains build up and eventually lead to the clinical features of AGU. AGU is one of seven identified Glycoprotein Storage Diseases.
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Clinical manifestations consist of psychomotor retardation, grotesque facial appearance, hepatosplenomegaly, ventral hernia and skeletal abnormalities. It is a member of Finnish disease heritage, a group of diseases or syndromes caused by mutation in a single gene characterized by higher frequency in Finland than the rest of the world.[1]
Deficiency of aspartylglucosaminidase (1-aspart-amido-beta-N-acetylglucosamine aminohydrase - E.C.3.5.1.26), an enzyme which cleaves the N-acetyl-glucosamine-asparagine linkage of oligosaccharide chains in glycoprotein and glycopeptide metabolism, causes Aspartylglycosaminuria. Biochemical tests show high urinary levels of aspartylglucosamine and low activity of aspartylglucosaminidase.
Aspartylglycosaminuria is most common in patients of Finnish ancestry, affecting about 1 in 17,000 people in Finland.[1]
After trisomy 21 and fragile X syndrome, this is the most frequent multiple congenital anomaly/mental retardation syndrome.[2]
The diagnosis of AGU is made initially by demonstrating increased concentrations of oliogosaccharides, short chains of sugars, that accumulate in the urine. The diagnosis is then confirmed by measuring the activity of the enzyme aspartylglucosaminidase in the blood or in a skin biopsy. Mutations can be demonstrated in this gene and used to screen prenatally.
Individuals with AGU typically have normal development in infancy. Around the age of 2–4 years, they begin showing signs of developmental delay, but development is still progressing. Initial symptoms may present as clumsiness and/or speech delay. Individuals with AGU also show increased upper respiratory infections. Development continues until about puberty, however, individuals at 13–16 years of age typically show mental and motor development similar to a 5-6 year old. Around puberty, a gradual decline in mental abilities and motor skills occurs. This progressive decline continues until about 25–28 years of age, when rapid impairment of abilities occurs, resulting in severe mental retardation.
There is no cure for AGU. Treatment is limited to reducing or controlling symptoms. For example, medication may control seizures. It is encouraged that individuals with AGU routinely see their genetic counselors, neurological, ophthalmological, and other specialists as symptoms arise, to maintain the control of their effects.
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