TY - JOUR
T1 - Argininosuccinic aciduria
T2 - From a monogenic to a complex disorder
AU - Erez, Ayelet
N1 - National Institutes of Health [K08 DK081735]This work was supported by National Institutes of Health grant K08 DK081735. The author thanks her mentor Prof Brendan Lee for his vision, guidance, and endless support; Sandesh C. S. Nagamani, a colleague and friend, for his valuable edits and illustrations; and the William K. Bowes, Jr. Award Committee for their generosity, recognition, and promotion of medical geneticists.
PY - 2013/4
Y1 - 2013/4
N2 - In the early 1930s, phenylketonuria was among the first metabolic diseases to be defined. In the following years, multiple attempts to correlate genotype and phenotype in several inherited metabolic diseases, including phenylketonuria, were encountered with difficulties. It is becoming evident that the phenotype of metabolic disorders is often more multifaceted than expected from the disruption of a specific enzyme function caused by a single-gene disorder. Undoubtedly, revealing the factors contributing to the discrepancy between the loss of a single enzymatic function and the wide spectrum of clinical consequences would allow clinicians to optimize treatment for their patients. This article discusses several possible contributors to the unique, complex phenotypes observed in inherited metabolic disorders, using argininosuccinic aciduria as a disease model.
AB - In the early 1930s, phenylketonuria was among the first metabolic diseases to be defined. In the following years, multiple attempts to correlate genotype and phenotype in several inherited metabolic diseases, including phenylketonuria, were encountered with difficulties. It is becoming evident that the phenotype of metabolic disorders is often more multifaceted than expected from the disruption of a specific enzyme function caused by a single-gene disorder. Undoubtedly, revealing the factors contributing to the discrepancy between the loss of a single enzymatic function and the wide spectrum of clinical consequences would allow clinicians to optimize treatment for their patients. This article discusses several possible contributors to the unique, complex phenotypes observed in inherited metabolic disorders, using argininosuccinic aciduria as a disease model.
UR - http://www.scopus.com/inward/record.url?scp=84875944923&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/gim.2012.166
DO - https://doi.org/10.1038/gim.2012.166
M3 - مقالة مرجعية
SN - 1098-3600
VL - 15
SP - 251
EP - 257
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 4
ER -