Aspartylglycosaminuria

Alternate names

Aspartylglucosaminuria; Aspartylglucosamidase (AGA) deficiency; AGU; AGA deficiency; Glycosylasparaginase deficiency

Definition

Aspartylglycosaminuria is a very rare lysosomal storage disease that causes a progressive decline in mental functioning.

Epidemiology

Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is less common outside of Finland, but the incidence is unknown.

Cause

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 complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins).

Gene mutations

• AGA gene mutations result in the absence or shortage 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 destruction of the cell.
• 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

Infants with aspartylglycosaminuria appear healthy at birth with signs and symptoms beginning around the age of 2 or 3.

Signs and symptoms

• Infants with aspartylglycosaminuria appear healthy at birth, and development is typcailly normal throughout childhood.
• The first sign of this condition, which becomes evident around the age of 2 or 3, is usually delayed speech.
• Mild intellectual disability then becomes apparent, and learning occurs at a slowed pace.
• Intellectual disability progressively worsens in adolescence.
• Most people with this disorder lose much of the speech they have learned, and affected adults usually have only a few words in their vocabulary.
• Adults with aspartylglucosaminuria may develop seizures or problems with movement.
• People with this condition may also have bones that become progressively weak and prone to fracture (osteoporosis), an unusually large range of joint movement (hypermobility), and loose skin.
• Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes (ocular hypertelorism), small ears, and full lips.
• The nose is short and broad and the face is usually square-shaped.
• Children with this condition may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short. Affected children also tend to have frequent upper respiratory infections.
• Individuals with aspartylglucosaminuria usually survive into mid-adulthood.
• The skeleton may also become deformed. T
• he spine may be twisted (scoliosis) and the neck may be unusually short.
• The eyes may also develop cataracts. Behavior problems are common.
• Lung, heart and blood problems tend to occur in later years.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormality of amino acid metabolism
• Aspartylglucosaminuria(High urine aspartylglucosamine levels)
• Delayed speech and language development(Deficiency of speech development)
• Dyskinesia(Disorder of involuntary muscle movements)
• Gingival overgrowth(Gum enlargement)
• Hypertelorism(Wide-set eyes)
• Intellectual disability(Mental deficiency)
• Large face(Big face)
• Mandibular prognathia(Big lower jaw)
• Microtia(Small ears)
• Neurological speech impairment(Speech disorder)
• Scoliosis
• Short nose(Decreased length of nose)
• Thick vermilion border(Full lips)
• Umbilical hernia
• Wide nasal bridge(Broad nasal bridge)

30%-79% of people have these symptoms

• Abnormal cortical bone morphology
• Abnormality of the ulna
• Anterior beaking of lumbar vertebrae
• Carious teeth(Dental cavities)
• Coarse facial features(Coarse facial appearance)
• Macroglossia(Abnormally large tongue)
• Macroorchidism(Large testis)
• Pectus carinatum(Pigeon chest)
• Thickened calvaria(Increased thickness of skull cap)

5%-29% of people have these symptoms

• Arthritis(Joint inflammation)
• Chronic otitis media(Chronic infections of the middle ear)
• Delayed skeletal maturation(Delayed bone maturation)
• Hepatomegaly(Enlarged liver)
• Inguinal hernia
• Joint stiffness(Stiff joint)
• Malabsorption(Intestinal malabsorption)
• Pes planus(Flat feet)
• Recurrent respiratory infections(Frequent respiratory infections)
• Seizure
• Sleep disturbance(Difficulty sleeping)
• Splenomegaly(Increased spleen size)
• Vascular skin abnormality

Diagnosis

• In order to be diagnosed with AGU an individual takes a urine test, which will show indication of an increased amount of aspartylglucosamin being secreted.
• The confirmation of the diagnosis of aspartylglucosaminuria requires a blood test.
• This helps show if the enzyme aspartylglucosaminidase is present or partially absent.
• A skin simple will also show the amount of aspartylglucosaminidase present.

NIH genetic and rare disease info

• NIH info on Aspartylglycosaminuria

Aspartylglycosaminuria is a rare disease.

Aspartylglycosaminuria Resources
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