title: Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family.
abstract: Aspartylglucosaminuria is a rare autosomal recessive lysosomal storage disorder leading early to a progressive intellectual disability. Monozygous Qatari twins presented with an unusual perinatal manifestation characterized by severe muscular hypotonia, scarce spontaneous movements, multiple contractures, and respiratory insufficiency. Biochemical investigations suggested aspartylglucosaminuria, and a novel homozygous mutation c.439T>C (p.S147P) was found in the aspartylglucosaminidase gene. However, it cannot be excluded that the unusual neonatal presentation is due to an additional autosomal recessive disease in this multiply consanguineous family. The classical aspartylglucosaminuria phenotype (progressive speech delay, psychomotor retardation, and behavioral abnormalities) was observed in 3 Turkish siblings. Although aspartylglucosaminuria was suspected early, the definite diagnosis was not confirmed until the age of 18 years. A novel homozygous mutation c.346C>T (p.R116W) was found. These 5 cases emphasize that aspartylglucosaminuria is panethnic and may possibly present with prenatal manifestation. Screening for aspartylglucosaminuria should be done in all patients with unexplained psychomotor retardation.
authors.affiliation: 1Department of Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ebinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Devjani
authors.initials: D
authors.lastname: Sengupta
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
authors.forename: Noora
authors.initials: N
authors.lastname: Shahbeck
authors.forename: Ute
authors.initials: U
authors.lastname: Moog
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.forename: Friederike
authors.initials: F
authors.lastname: Bürger
authors.forename: Dorothea
authors.initials: D
authors.lastname: Haas
authors.forename: Peter
authors.initials: P
authors.lastname: Ruef
authors.forename: Inga
authors.initials: I
authors.lastname: Harting
authors.forename: Hilal
authors.initials: H
authors.lastname: Al-Rifai
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
mesh_terms: D000293:Adolescent; D054880:Aspartylglucosaminuria / Q000235:genetics*; D001227:Aspartylglucosylaminase / Q000235:genetics*; D001921:Brain / Q000473:pathology; D003241:Consanguinity; D004569:Electroencephalography; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics*; D011780:Qatar; D014421:Turkey; D014427:Twins / Q000235:genetics
chemical_list: D001227:Aspartylglucosylaminase