TY - JOUR
T1 - Adult GAMT deficiency: A literature review and report of two siblings
AU - Modi, Bhavi P.
AU - Khan, Haq Nawaz
AU - van der Lee, Robin
AU - Wasim, Muhammad
AU - Haaxma, Charlotte A.
AU - Richmond, Phillip A.
AU - Drögemöller, Britt
AU - Shah, Suleman
AU - Salomons, Gajja
AU - van der Kloet, Frans M.
AU - Vaz, Fred M.
AU - van der Crabben, Saskia N.
AU - Ross, Colin J.
AU - Wasserman, Wyeth W.
AU - van Karnebeek, Clara D. M.
AU - Awan, Fazli Rabbi
N1 - Funding Information: Funding to C.D.M.v.K was provided by the BC Children's Hospital Foundation, Canadian Institutes of Health Research (grant number #301221) and a Foundation Metakids salary award. Part of this study was supported by a research project, “ Diagnosis of treatable inborn metabolic disorders of intellectual disability ” (Project No. CRP/PAK14- 02; Contract No. CRP/14/012 ) funded by the International Center for Genetic Engineering and Biotechnology (ICGEB), Italy [PI: Dr. Fazli Rabbi Awan]. CJR is supported by the Michael Smith Foundation for Health Research scholar award. Publisher Copyright: © 2021 The Authors
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait. Exome sequencing identified a homozygous nonsense variant in GAMT: NM_000156.5:c.134G>A (p.Trp45*). We also performed a literature review and compiled the genetic and clinical characteristics of all adult cases of GAMT deficiency reported to date. When compared to the adult cases previously reported, the musculoskeletal phenotype and the rapidly progressive nature of neurological and motor decline seen in our patients is striking. This study presents an opportunity to gain insights into the adult presentation of GAMT deficiency and highlights the need for in-depth evaluation and reporting of clinical features to expand our understanding of the phenotypic spectrum.
AB - Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait. Exome sequencing identified a homozygous nonsense variant in GAMT: NM_000156.5:c.134G>A (p.Trp45*). We also performed a literature review and compiled the genetic and clinical characteristics of all adult cases of GAMT deficiency reported to date. When compared to the adult cases previously reported, the musculoskeletal phenotype and the rapidly progressive nature of neurological and motor decline seen in our patients is striking. This study presents an opportunity to gain insights into the adult presentation of GAMT deficiency and highlights the need for in-depth evaluation and reporting of clinical features to expand our understanding of the phenotypic spectrum.
KW - Adult cases
KW - GAMT
KW - Guanidinoacetate methyltransferase deficiency
KW - Progressive intellectual and neurological deterioration
UR - http://www.scopus.com/inward/record.url?scp=85112865962&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ymgmr.2021.100761
DO - https://doi.org/10.1016/j.ymgmr.2021.100761
M3 - Article
C2 - 33996490
SN - 2214-4269
VL - 27
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100761
ER -