Paula and Bobby
Parents of Lillie
What is Aspartylglucosaminuria?
Aspartylglucosaminuria is a progressive genetic disorder.
Children born with the syndrome are healthy at birth, and symptoms usually develop from the age of 2 years or older.
Symptoms tend to worsen with the onset of puberty.
This syndrome is also known as:
Aga Deficiency AGU Aspartylglucosaminidase Deficiency; Aspartylglycosaminuria Glycoasparaginase; Glycosylasparaginase Deficiency
What gene change causes Aspartylglucosaminuria?
This rare disease is the result of a defect in the AGA gene which provides the instructions to produce the aspartylglucosaminidase enzyme.
As a lysosomal storage disease, neurological, skeletal and connective tissue are all affected.
It is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms, but have a 25% chance of passing the copies of the gene mutations onto each of their children.
what are the main symptoms of Aspartylglucosaminuria?
Symptoms of the syndrome usually present post infancy, and from the age of 2-3 years. Children who appeared to be developing typically may start to experience delays in speech leading to an eventual loss of speech already learnt. A decline in cognitive ability is a major symptom and this declice worsens with the age of the individual.
Physical features of the syndrome include widely-spaced eyes, small ears, full lips, a short and broad nose, square face, large head and rounded cheeks.
Other possible health conditions related to the syndrome include seizures, hypermobility, osteoporosis and respiratory infections.
Possible clinical traits/features:
Pes planus, Otitis media, Pathologic fracture, Pectus carinatum, Platyspondyly, Seizure, Autosomal recessive inheritance, Wide mouth, Diarrhea, Developmental regression, Limitation of joint mobility, Delayed skeletal maturation, Craniofacial hyperostosis, Coarse facial features, Dysostosis multiplex, Aspartylglucosaminuria, Umbilical hernia, Spasticity, Thick lower lip vermilion, Microcephaly, Scoliosis, Thickened calvaria, Spondylolisthesis, Spondylolysis, Sleep disturbance, Vacuolated lymphocytes, Splenomegaly, Recurrent respiratory infections, Arthritis, Abnormality of movement, Abnormality of metabolism/homeostasis, Abnormality of the outer ear, Abnormality of the ulna, Abnormality of the tongue, Broad face, Brachycephaly, Cataract, Carious teeth, Angiokeratoma corporis diffusum, Acne, Cerebral atrophy, Hoarse voice, Hernia, Short stature, Hepatomegaly, Hypoplastic frontal sinuses, Malabsorption, Delayed speech and language development, Gingival overgrowth, Beaking of vertebral bodies, Depressed nasal bridge
How does someone get tested for Aspartylglucosaminuria?
The initial testing for Aspartylglucosaminuria (AGU) syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Aspartylglucosaminuria
This condition needs to be considered in the differential diagnosis of the mucopolysaccharidoses and the mucolipidoses. Liver and cardiac involvement do occur but are uncommon; angiokeratoma corporis diffusum has been described. Arvio et al., (1993) summarised the early clinical symptoms in this condition. They note that recurrent respiratory infections are characteristic, as are umbilical and inguinal hernias, delayed speech, attention deficits, clumsiness and aggressive behaviour. The early facial features are described as ""a sagging face with a low bridge of the nose and a big mouth"". Arvio et al., (1999) point out that mucosal overgrowth (gum hypertrophy) and angiofibromas of the face are common features. Arvio et al., (2004) review the facial dysmorphology.
The vast majority of cases have been described in Finland, but a handful of patients have no Finnish ancestry.
This lysosomal storage disorder is first suspected by finding vacuolated lymphocytes in the blood and oligosaccharides in the urine, and can be confirmed by thin layer chromotography of urine and enzymology.
Engelen et al., (1992) localized the gene to 4q33-q35 by demonstrating hemizygous enzyme levels in a girl deleted for that chromosomal region. Mutations in the gene have been reported (Ikonen et al., 1993; Peltola et al., 1994; Peltola et al., 1996; Laitinen et al., 1997). In Finland one point mutation is responsible for 98% of abnormal alleles, but in non-Finnish cases there are a number of different mutations (Park et al., 1993).
Arvio and Mononen in 2016 reviewed clinical features of aspartylglucosaminuria. Overgrowth and macrocephaly were the most common features until five years old; around 16-19 years short stature was apparent. Some females were obese. At puberty, early menarche in females and macroorchidism in males was present. Cognition and motor skills were frequently normal at two years, but deteriorated thereafter; affected individuals were profoundly delayed at 45 years. Abnormal facial features evolved with time including broad mandible, short broad nose, large tongue, broad dental arches, gingival overgrowth, full cheeks, periorbital fullness coarsening of face and thick and full lips. Skin abnormalities were facial erythema, piezogenic papules in heels, facial seborrhea, facial angiofibromas, facial rosacea, depigmentation spots and loose skin. Connective tissue abnormalities included hernia, pes planovalgus, clubfoot, tapered fingers, lordosis, bulging abdomen, genu valgum, thoracic deformity, and contractures of fingers and elbows. Other abnormalities included hypotonia, respiratory infections, diarrhea, benign subcutaneous tumors, rheumatoid arthritis, psychosis, seizures, confusion, osteoporosis, bursitis, abscesses, fistulas, anemia and cardiac insufficiency. Typical brain MRI abnormalities were cerebral and cerebellar atrophy.
* This information is courtesy of the L M D
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