Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients

Introduction: Combined malonic and methylmalonic aciduria (CMAMMA) is a rare metabolic disease caused by biallelic variants in ACSF3 gene. The clinical phenotype is highly heterogeneous in this disorder, ranging from asymptomatic to severe symptoms. No cases with CMAMMA were reported in China.Materi...

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Autores principales:	Ping Wang, Jianbo Shu, Chunyu Gu, Xiaoli Yu, Jie Zheng, Chunhua Zhang, Chunquan Cai
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	combined malonic and methylmalonic aciduria ACSF3 gene benign condition Chinese population novel variant Pediatrics RJ1-570
Acceso en línea:	https://doaj.org/article/87a03c6b297c49cbb866b1c01c71d78c
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spelling	oai:doaj.org-article:87a03c6b297c49cbb866b1c01c71d78c2021-12-01T03:38:07ZCombined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients2296-236010.3389/fped.2021.751895https://doaj.org/article/87a03c6b297c49cbb866b1c01c71d78c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fped.2021.751895/fullhttps://doaj.org/toc/2296-2360Introduction: Combined malonic and methylmalonic aciduria (CMAMMA) is a rare metabolic disease caused by biallelic variants in ACSF3 gene. The clinical phenotype is highly heterogeneous in this disorder, ranging from asymptomatic to severe symptoms. No cases with CMAMMA were reported in China.Materials and Methods: In this study, three Chinese pediatric patients were diagnosed with CMAMMA unexpectedly while being treated for other ailments. To better characterize CMAMMA in a Chinese population, we made a multidimensional analysis with detailed clinical phenotype, semi-quantitative detection of urine organic acid, and analysis of ACSF3 gene variants.Results: The clinical presentation of these patients is quite different; their main complaints were anemia, jaundice, or abnormal urine test, respectively. They showed no symptoms of the classic methylmalonic academia, but urine organic acid analysis showed elevated malonic acid and methylmalonic acid in all the patients repeatedly. Variants were found at four sites in ACSF3 gene. Patient 1 carried the compound heterogeneous variant c.689G> A (p.Trp230*)/c.1456G> A (p.Ala486Thr). A compound heterozygous variant c.473C> T (p.Pro158Leu)/c.1456G> A (p.Ala486Thr) was identified in patient 2. Patient 3 harbored a novel homozygous variant c.1447A> G (p.Lys483Glu).Conclusions: Three Chinese patients were diagnosed with CMAMMA caused by ACSF3 variants. Their clinical course revealed that CMAMMA can be a benign condition that does not affect individual growth and development, but severe clinical phenotype may appear when other triggers exist. This study systematically elaborates CMAMMA in a Chinese population for the first time, broadens the spectrum of gene variant, and provides a strong basis for the etiological study of this disorder.Ping WangPing WangJianbo ShuJianbo ShuChunyu GuChunyu GuChunyu GuXiaoli YuJie ZhengJie ZhengChunhua ZhangChunquan CaiChunquan CaiChunquan CaiFrontiers Media S.A.articlecombined malonic and methylmalonic aciduriaACSF3 genebenign conditionChinese populationnovel variantPediatricsRJ1-570ENFrontiers in Pediatrics, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	combined malonic and methylmalonic aciduria ACSF3 gene benign condition Chinese population novel variant Pediatrics RJ1-570
spellingShingle	combined malonic and methylmalonic aciduria ACSF3 gene benign condition Chinese population novel variant Pediatrics RJ1-570 Ping Wang Ping Wang Jianbo Shu Jianbo Shu Chunyu Gu Chunyu Gu Chunyu Gu Xiaoli Yu Jie Zheng Jie Zheng Chunhua Zhang Chunquan Cai Chunquan Cai Chunquan Cai Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
description	Introduction: Combined malonic and methylmalonic aciduria (CMAMMA) is a rare metabolic disease caused by biallelic variants in ACSF3 gene. The clinical phenotype is highly heterogeneous in this disorder, ranging from asymptomatic to severe symptoms. No cases with CMAMMA were reported in China.Materials and Methods: In this study, three Chinese pediatric patients were diagnosed with CMAMMA unexpectedly while being treated for other ailments. To better characterize CMAMMA in a Chinese population, we made a multidimensional analysis with detailed clinical phenotype, semi-quantitative detection of urine organic acid, and analysis of ACSF3 gene variants.Results: The clinical presentation of these patients is quite different; their main complaints were anemia, jaundice, or abnormal urine test, respectively. They showed no symptoms of the classic methylmalonic academia, but urine organic acid analysis showed elevated malonic acid and methylmalonic acid in all the patients repeatedly. Variants were found at four sites in ACSF3 gene. Patient 1 carried the compound heterogeneous variant c.689G> A (p.Trp230*)/c.1456G> A (p.Ala486Thr). A compound heterozygous variant c.473C> T (p.Pro158Leu)/c.1456G> A (p.Ala486Thr) was identified in patient 2. Patient 3 harbored a novel homozygous variant c.1447A> G (p.Lys483Glu).Conclusions: Three Chinese patients were diagnosed with CMAMMA caused by ACSF3 variants. Their clinical course revealed that CMAMMA can be a benign condition that does not affect individual growth and development, but severe clinical phenotype may appear when other triggers exist. This study systematically elaborates CMAMMA in a Chinese population for the first time, broadens the spectrum of gene variant, and provides a strong basis for the etiological study of this disorder.
format	article
author	Ping Wang Ping Wang Jianbo Shu Jianbo Shu Chunyu Gu Chunyu Gu Chunyu Gu Xiaoli Yu Jie Zheng Jie Zheng Chunhua Zhang Chunquan Cai Chunquan Cai Chunquan Cai
author_facet	Ping Wang Ping Wang Jianbo Shu Jianbo Shu Chunyu Gu Chunyu Gu Chunyu Gu Xiaoli Yu Jie Zheng Jie Zheng Chunhua Zhang Chunquan Cai Chunquan Cai Chunquan Cai
author_sort	Ping Wang
title	Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
title_short	Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
title_full	Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
title_fullStr	Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
title_full_unstemmed	Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients
title_sort	combined malonic and methylmalonic aciduria due to acsf3 variants results in benign clinical course in three chinese patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/87a03c6b297c49cbb866b1c01c71d78c
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Combined Malonic and Methylmalonic Aciduria Due to ACSF3 Variants Results in Benign Clinical Course in Three Chinese Patients

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