Mutations and polymorphisms in the human argininosuccinate lyase (ASL) gene

Balmer, Cécile; Pandey, Amit Vikram; Rüfenacht, Véronique; Nuoffer, Jean-Marc; Fang, Ping; Wong, Lee-Jun; Häberle, Johannes (2014). Mutations and polymorphisms in the human argininosuccinate lyase (ASL) gene. Human mutation, 35(1), pp. 27-35. Wiley-Blackwell 10.1002/humu.22469

[img] Text
2014_Human_Mutation.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

Argininosuccinate lyase deficiency (ASLD) is caused by a defect of the urea cycle enzyme argininosuccinate lyase (ASL) encoded by the ASL gene. Patients often present early after birth with hyperammonemia but can also manifest outside the neonatal period mainly triggered by excessive protein catabolism. Clinical courses comprise asymptomatic individuals who only excrete the biochemical marker, argininosuccinic acid, in urine, and patients who succumb to their first hyperammonemic decompensation. Some patients without any hyperammonemia develop severe neurological disease. Here, we are providing an update on the molecular basis of ASLD by collecting all published (n = 67) as well as novel mutations (n = 67) of the ASL gene. We compile data on all 160 different genotypes ever identified in 223 ASLD patients, including clinical courses whenever available. Finally, we are presenting structural considerations focusing on the relevance of mutations for ASL homotetramer formation. ASLD can be considered as a panethnic disease with only single founder mutations identified in the Finnish (c.299T>C, p.Ile100Thr) and Arab (c.1060C>T, p.Gln354*) population. Most mutations are private with only few genotypes recurring in unrelated patients. The majority of mutations are missense changes including some with more frequent occurrence such as p.Arg12Gln, p.Ile100Thr, p.Val178Met, p.Arg186Trp, p.Glu189Gly, p.Gln286Arg, and p.Arg385Cys.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Pandey, Amit Vikram, Nuoffer, Jean-Marc


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology






[4] Swiss National Science Foundation


[102] Pathogenesis of disorders caused by human P450 oxidoreductase mutations Official URL




Amit Vikram Pandey

Date Deposited:

05 Jun 2014 10:25

Last Modified:

06 Jan 2023 17:10

Publisher DOI:


Related URLs:

PubMed ID:


Uncontrolled Keywords:

ASA, ASL argininosuccinate lyase, argininosuccinic aciduria, hyperammonemia




Actions (login required)

Edit item Edit item
Provide Feedback