title: Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.
abstract: Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).
authors.affiliation: Biochemical Genetic Unit, Department of Genetics, Kuala Lumpur Hospital, Jalan Pahang 50586, Malaysia. beechinmy@yahoo.com
authors.forename: Bee Chin
authors.initials: BC
authors.lastname: Chen
authors.forename: Ivan N
authors.initials: IN
authors.lastname: McGown
authors.forename: Meow Keong
authors.initials: MK
authors.lastname: Thong
authors.forename: James
authors.initials: J
authors.lastname: Pitt
authors.forename: Zabedah M
authors.initials: ZM
authors.lastname: Yunus
authors.forename: Teck Beng
authors.initials: TB
authors.lastname: Khoo
authors.forename: Lock Hock
authors.initials: LH
authors.lastname: Ngu
authors.forename: John A
authors.initials: JA
authors.lastname: Duley
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000652:urine; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics; D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000652:urine; D001321:Autistic Disorder; D015415:Biomarkers / Q000652:urine; D002657:Child Development; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008296:Malaysia; D008297:Male; D009154:Mutation; D009207:Myoclonus / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D011237:Predictive Value of Tests; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000235:genetics; D011597:Psychomotor Performance; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D012263:Ribonucleosides / Q000652:urine; D012640:Seizures / Q000175:diagnosis / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D012263:Ribonucleosides; C043566:succinylaminoimidazole carboxamide riboside; C012168:adenylosuccinate; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; C043565:succinyladenosine; D000264:Adenylosuccinate Lyase; D000241:Adenosine