title: [A family with two children diagnosed with aspartylglucosaminuria-case report and literature review].
abstract: OBJECTIVE
  The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria.
  
  
  METHODS
  Clinical data of two pediatric siblings in a family were analyzed retrospectively and relative literature was reviewed in order to study the clinical features, imaging and enzymatic characteristics and genetic mutations.
  
  
  RESULTS
  Case 1, the proband, male, he was hospitalized at 20 months of age because of fever and hepatosplenomegaly for nine days. This child was of moderate nutritional status and normal development. Blood tests showed hemoglobin 78.0 g/L, RBC3.18 × 10¹²/L, WBC 4.06 × 10⁹/L, neutrophils 0.236, lymphocytes 0.631, platelets 34 × 10⁹/L, C-reactive protein 17 mg/L. Blood biochemistry showed alanine aminotransferase 67.1 U/L, aspartate aminotransferase 74.1 U/L, serum albumin 32.8 g/L, direct bilirubin 10.5 µmol/L, lactate dehydrogenase 301.7 U/L. Bone marrow cytology showed reactive morphological changes in bone marrow cells. Atypical lymphocytes could be seen in both peripheral blood and bone marrow smears. Cranial MRI showed poor myelination. Aspartylglucosaminidase activity in peripheral leucocytes of the proband 5.7 nmol/(g × min) vs. normal control>26.6 nmol/(g × min). On his AGA gene and that of his parents, a heterozygous mutation site located in exon 3, c.392C>T (p.S131L), was identified as a novel mutation inherited from his father. The mutation from his mother has not been detected. The proband was not responsive to the anti-infectious medication, nutritional intervention and symptomatic treatment.He died one month after diagnosis.His elder brother, Case 2, showed fever, recurrent respiratory tract infection and progressive psychomotor regression with hepatosplenomegaly from the age of four years. Cranial MRI revealed extensive symmetrical leukodystrophy in bilateral cerebra, cerebellum and brainstem.He died at the age of six years.Related literature was summarized, and no Chinese AGU cases had been reported; 221 foreign cases were collected. The clinical and imaging characteristics were summarized. Delay in language development was one of the clinical symptoms that the majority of parents of AGU children first noted.
  
  
  CONCLUSIONS
  Patients with aspartylglucosaminuria lack of specific symptoms.For children with unexplained delayed speech and progressive mental retardation, the possibility of AGU should be considered, and efforts be made for enzymatic and genetic diagnosis. c.392C> T (p.S131L) was identified as a novel mutation of AGA gene.
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China. Email: zouliping21@hotmail.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Xiaoqiao
authors.initials: X
authors.lastname: Chen
mesh_terms: D054880:Aspartylglucosaminuria / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D001227:Aspartylglucosylaminase / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016464:Lysosomal Storage Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D001227:Aspartylglucosylaminase