TY - JOUR
T1 - Alström syndrome
T2 - Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center
AU - Waldman, Meryl
AU - Han, Joan C.
AU - Reyes-Capo, Daniela P.
AU - Bryant, Joy
AU - Carson, Kathryn A.
AU - Turkbey, Baris
AU - Choyke, Peter
AU - Naggert, Jürgen K.
AU - Gahl, William A.
AU - Marshall, Jan D.
AU - Gunay-Aygun, Meral
N1 - Funding Information:
We thank Alström Syndrome International (ASI) for their extensive support and the patients and their families who generously participated in this investigation. Support was provided by the Intramural Research Programs of the National Human Genome Research Institute (Z99 HG999999), the National Institute of Child Health and Human Development (ZIAHD00641, ZIAHD008898), the NIH Clinical Center, (HD36878) Bethesda, MD, USA and Johns Hopkins Institute for Clinical and Translational Research, (UL1 TR001079 from the National Center for Advancing Translational Sciences). This paper is dedicated to the memory of our colleague, Jan Davis Marshall, who worked tirelessly to improve the lives of patients with Alström syndrome and made numerous important scientific contributions during her lifelong career at The Jackson Laboratory (HD36878)
Funding Information:
We thank Alström Syndrome International (ASI) for their extensive support and the patients and their families who generously participated in this investigation. Support was provided by the Intramural Research Programs of the National Human Genome Research Institute ( Z99 HG999999 ), the National Institute of Child Health and Human Development ( ZIAHD00641 , ZIAHD008898 ), the NIH Clinical Center , ( HD36878 ) Bethesda, MD, USA and Johns Hopkins Institute for Clinical and Translational Research , ( UL1 TR001079 from the National Center for Advancing Translational Sciences ). This paper is dedicated to the memory of our colleague, Jan Davis Marshall, who worked tirelessly to improve the lives of patients with Alström syndrome and made numerous important scientific contributions during her lifelong career at The Jackson Laboratory ( HD36878 )
Publisher Copyright:
© 2018
PY - 2018/9
Y1 - 2018/9
N2 - Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m 2 and proteinuria); all were adults with median age of 32.8 (20.6–37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.
AB - Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m 2 and proteinuria); all were adults with median age of 32.8 (20.6–37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.
KW - ALMS1
KW - Alström syndrome
KW - Chronic kidney disease
KW - Ciliopathy
KW - Insulin resistance
KW - Metabolic syndrome
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U2 - 10.1016/j.ymgme.2018.07.010
DO - 10.1016/j.ymgme.2018.07.010
M3 - Article
C2 - 30064963
AN - SCOPUS:85050619360
SN - 1096-7192
VL - 125
SP - 181
EP - 191
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 1-2
ER -