Aspartylglucosaminuria is a progressive genetic disorder belonging to the group of lysosomal storage diseases, with progressive mental retardation appearing in early infancy and childhood, being the main clinical feature. Additional symptoms involving the central nervous system, soft tissues, and various other organs may be evident. A thorough diagnostic workup is necessary in order to make the diagnosis.
Symptoms in aspartylglucosaminuria arise due to the deficiency of the enzyme aspartylglucosaminidase (AGA), an essential component in the process of oligosaccharide degradation . Consequently, accumulation of oligosaccharides (specifically glycoasparagine) in various body tissues, primarly the central nervous system occurs, which is why mental retardation, developing in the first several years of life, is the most prominent clinical feature  . The diagnosis is most frequently made between 5-6 years of age . The decline of mental functions is progresses slowly throughout puberty and early adulthood, with rapid deterioration after 30 years of age and life expectancy is usually below 45 years of age  . Progression seems to be slower in females, and due to the founder effect, this autosomal recessive condition is almost exclusively seen in the Finnish population   . An increased head circumference that shrinks with age (due to slow decay of brain cells) and a growth spurt during infancy are two most common accompanying signs, whereas the appearance of hernias, recurrent respiratory infections, delayed speech and cognitive development, gingival hyperplasia, and facial coarsening is reported as well   . Additional musculoskeletal (thickening of the ribs and skull, lordosis, vertebral dysplasia, contractures in fingers and elbows, a knock knee, muscle atrophy and hypotonia) and cutaneous (angiokeratomas, erythema and seborrheic dermatitis on the face) signs may be encountered, while many patients experience psychotic symptoms, restlessness, confusion and other psychiatric manifestations    . Moreover, hepatosplenomegaly, cardiomyopathy, and macroorchidism, but also epilepsy and abnormal paroxysmal motor events during sleep can comprise the clinical presentation of aspartylglucosaminuria  . In approximately 7% of cases, joint involvement is observed, mainly in the form of chronic arthritis .
A detailed patient history is the first and fundamental step for the diagnosis of aspartylglucosaminuria. Although pregnancy, perinatal period and early infancy are uneventful , the onset of mental retardation and accompanying facial, skeletal or other notable features in individuals of Finnish ancestry must prompt the physician to exclude this lysosomal storage disease as a possible cause . More importantly, a complete family history may reveal similar findings in siblings or close relatives (due to the autosomal recessive pattern of inheritance), while consanguineous marriages are also an important risk factor  . After a detailed physical examination and confirmation of central nervous system complaints, magnetic resonance imaging (MRI) of the endocranium, a procedure that solidifies its importance when it comes to the diagnosis of aspartylglucosaminuria, is recommended, and will show hyperintensity of white matter and hypointensity of the thalamus on T2-weighed images, as well as brain atrophy  . On the other hand, laboratory investigations in the form of urine and serum testing is a more specific diagnostic method, comprised of detection of oligosaccharides and subsequent molecular analysis that will determine the activity of glycosylasparaginase, an enzyme necessary for their degradation  . Finally, genetic testing to confirm mutations in the aspartylglucosaminidase (AGA) gene on chromosome 4q32-q33.1 is performed, and in the setting of a known mutation in one or both parents, a prenatal diagnosis from chorionic villus or amniotic fluid samples can be achieved  .