Aspartylglucosaminuria (Aspartylglycosylaminase Defic)

Autosomal recessive - en[1]

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 [1]. 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 [2] [3]. The diagnosis is most frequently made between 5-6 years of age [2]. 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 [4] [5]. 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 [2] [5] [6]. 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 [2] [4] [7]. 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 [2] [3] [4] [5]. Moreover, hepatosplenomegaly, cardiomyopathy, and macroorchidism, but also epilepsy and abnormal paroxysmal motor events during sleep can comprise the clinical presentation of aspartylglucosaminuria [2] [7]. In approximately 7% of cases, joint involvement is observed, mainly in the form of chronic arthritis [5].

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  • Ears
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  • musculoskeletal
    • 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.[]
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  • neurologic
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  • Face, Head & Neck
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  • Entire body system
    Recurrent Infection
    • Most of the reported cases have been in Finland. as·par·tyl·gly·cos·a·mi·nu·ri·a ( as-par'til-glī-kō'să-min-yū'rē-ă ) [MIM*208400] A lysosomal disorder caused by deficiency of aspartoglucosaminidase; involves recurrent infections and diarrhea; mental[]
    • He was investigated at another medical center for recurrent infections and splenomegaly at three years of age.[]
    • The infantile form (type i) features psychomotor deterioration, muscle spasticity, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, seizures, recurrent infections, and macroglossia, with death occurring in the first decade[]
    • During early childhood recurrent infections of the ear and upper respiratory system are common.[]
    Short Stature
    • Symptoms of Aspartylglucosaminuria Normal development during first few years of life Short stature Small skull Clumsiness Delayed speech more symptoms...»[]
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  • Jaw & Teeth
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  • Workup

    A detailed patient history is the first and fundamental step for the diagnosis of aspartylglucosaminuria. Although pregnancy, perinatal period and early infancy are uneventful [2], 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 [6]. 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 [2] [4]. 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 [2] [8]. 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 [2] [4]. 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 [2] [4].


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  • Imaging

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  • Treatment



    Fragile X Syndrome
    • X syndrome , this is the most frequent multiple congenital anomaly/mental retardation syndrome in Finland. [6] See also [ edit ] Inborn error of metabolism References [ edit ] External links [ edit ] Aspartylglycosaminuria at NIH 's Office of Rare Diseases[]



    Sex distribution
    Age distribution




    Patient Information

    Other symptoms

    Mutation in the AGA Gene
    Loss of Speech
    • Facial features change progressively; this may include: thickening of the skin features becoming more prominent large head broad lower jaw short, broad nose rounded cheeks [2] Progression of developmental and mental disabilities, including: progressive loss[]
    Small Ears
    • Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes ( ocular hypertelorism ), small ears , and full lips.[]


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    1. Opladen T, Ebinger F, Zschocke J, et al. Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family. J Child Neurol. 2014;29(1):36-42.
    2. Arvio M, Mononen I. Aspartylglycosaminuria: a review. Orphanet J Rare Dis. 2016;11:162.
    3. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
    4. Tokola AM, Åberg LE, Autti TH. Brain MRI findings in aspartylglucosaminuria. J Neuroradiol. 2015;42(6):345-357.
    5. Arvio M, Laiho K, Kauppi M, et al. Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis. Ann Rheum Dis. 2002;61(2):180-181.
    6. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
    7. Ambrosetto G, Santucci M. Sleep-related hypermotor seizures in aspartylglucosaminuria: a case report. Epilepsia. 2009;50(6):1638-1640.
    8. Sui L, Lakshminarasimhan D, Pande S, Guo H-C. Structural basis of a point mutation that causes the genetic disease Aspartylglucosaminuria. Structure. 2014;22(12):1855-1861.

    1. Leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type - W Krivit, C Peters, EG Shapiro - Current opinion in neurology, 1999 -

    Media References

    1. Autosomal recessive - en, CC BY-SA 3.0


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