Dados do Trabalho

Título

ASPARTYGLICOSAMINURIA, THE DISEASE OF KING CHARLES II: A CASE REPORT

Apresentação do caso único

BVF, 11 years old, mother used drugs during pregnancy, unknown father, adopted at 2 years old. Developmental delay noted from the start, walked at 4 years, and talked at 5 years. Investigation began at 4 years old. Cranial MRI showed signs of periventricular leukomalacia and diffuse thinning of the corpus callosum. Due to repeated episodes of the common cold and otitis, adenoidectomy and tonsillectomy were performed at 5 years old. During a cardiological evaluation, a bicuspid aortic valve with significant moderate insufficiency and mild mitral insufficiency were identified. Physical examination revealed an infiltrated face, epicanthal folds, and poorly preserved teeth. Initially, mucopolysaccharidosis was suspected, but tests were inconclusive. Subsequently, whole exome sequencing identified a pathogenic mutation in the AGA gene (C.698+1G>T) compatible with aspartylglucosaminuria.

Discussão

Aspartylglucosaminuria belongs to the group of lysosomal storage diseases and occurs due to a mutation in the AGA gene on chromosome 4 (4q34.3), resulting in a lack or low activity of the enzyme aspartylglucosaminidase (1). Its absence leads to the accumulation of undegraded glycoproteins within cells of tissues such as the brain, liver, and lymph nodes. The disease is inherited in an autosomal recessive manner, highlighting the importance of family history in establishing diagnoses of neurological diseases, which is absent in this case due to the family dynamics. To date, about 300 cases have been described worldwide. The most prevalent symptoms are umbilical and inguinal hernias, as well as recurrent upper respiratory tract infections and otitis (2). Physical examination may reveal hepatomegaly or splenomegaly and dental destruction on oroscopy. It is common for children to present a similar phenotype marked by macrocephaly, a short and wide nose, and facial flushing. Speech and language development are generally delayed, and cognitive development is slow during the preschool and school years, with intellectual deficits often associated.

Comentários finais

Aspartylglucosaminuria is a metabolic disease that leads to varying degrees of motor and intellectual disabilities. After clinical suspicion, evidence of elevated levels of aspartylglucosamine in the urine is a strong indicator of the disease and should be analyzed along with serum levels of enzyme activity in leukocytes and fibroblasts. Currently, treatment is supportive, but enzyme replacement therapies and gene therapies are under study (3).

Referências

1) Arvio P, Arvio M. Progressive nature of aspartylglucosaminuria. Acta Paediatr 2002; 91: 255-257.

2) Arvio M, Mononen I. Aspartylglycosaminuria: a review. Orphanet J Rare Dis 2016; 11: 162.

3) Banning A, Schiff M, Tikkanen R. Amlexanos provides a potential therapy for nonsense mutations in the lysosomal storage disorder Aspartylglucosaminouria. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 668-675.

Palavras Chave

Aspartylglucosaminuria; lysosomal storage diseases; intellectual deficits