Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

Margutti, Ana Vitoria Barban; Silva, Wilson A.; Garcia, Doroti de Oliveira; Molfetta, Greice Andreotti de; Marques, Adriana Aparecida; Amorim, Tatiana; Prazeres, Vânia Mesquita Gadelha; Silva, Raquel Tavares Boy da; Miura, Irene Kazue; Neto, João Seda; Santos, Emerson de Santana; Santos, Mara Lúcia Schmitz Ferreira; Lourenço, Charles Marques; Tonon, Tássia; Sperb‐Ludwig, Fernanda; Souza, Carolina Fischinger Moura de; Schwartz, Ida Vanessa Döederlein; Camelo, José Simon

doi:10.21203/rs.2.17565/v1

Cited by 2 publications

(2 citation statements)

References 19 publications

(25 reference statements)

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“…As a result, there is a decreased catabolism of branched‐chain amino acids, particularly, leucine, valine and isoleucine. It leads to their accumulation in the blood, which commonly progresses to metabolic encephalopathy if they remain undiagnosed for a longer period 106 . In a case report by Patil et al., a 17‐day‐old boy was the firstborn of non‐consanguineous parents.…”

Section: Glioblastomamentioning

confidence: 99%

Metabolomics of neurological disorders in India

Gupta

Sharma

2021

Analytical Science Advances

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Metabolomics is the comprehensive study of the metabolome and its alterations within biological fluids and tissues. Over the years, applications of metabolomics have been explored in several areas, including personalised medicine in diseases, metabolome‐wide association studies (MWAS), pharmacometabolomics and in combination with other branches of omics such as proteomics, transcriptomics and genomics. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the major analytical techniques widely employed in metabolomics. In addition, MS is coupled with chromatography techniques like gas chromatography (GC) and liquid chromatography (LC) to separate metabolites before analysis. These analytical techniques have made possible identification and quantification of large numbers of metabolites, encompassing characterization of diseases and facilitating a systematic and rational therapeutic strategy based on metabolic patterns. In recent years, the metabolomics approach has been used to obtain a deeper insight into the underlying biochemistry of neurodegenerative disorders and the discovery of biomarkers of clinical implications. The current review mainly focuses on an Indian perspective of metabolomics for the identification of metabolites and metabolic alterations serving as potential diagnostic biomarkers for neurological diseases including acute spinal cord injury, amyotrophic lateral sclerosis, tethered cord syndrome, spina bifida, stroke, Parkinson's disease, glioblastoma and neurological disorders with inborn errors of metabolism.

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Section: Glioblastomamentioning

confidence: 99%

Metabolomics of neurological disorders in India

Gupta

Sharma

2021

Analytical Science Advances

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“…7 BCKDHA consists of nine exons and is located on Chromosome 19q13.2. 8 Although many MSUD-causing variants have been identified in BCKDHA, 5,9 no structural rearrangements have been reported as causative of MSUD. Herein, we describe the classic form of MSUD with paracentric inversion of Chromosome 19, which disrupts BCKDHA, and present evidence derived from molecular tests.…”

Section: Introductionmentioning

confidence: 99%

Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA: A case report

et al. 2022

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Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched‐chain amino acid metabolism caused by mutations in BCKDHA, BCKDHB, and DBT that encode the E1α, E1β, and E2 subunits of the branched‐chain α‐ketoacid dehydrogenase (BCKD) complex. Various MSUD‐causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA: a missense variant (NM_000709.3:c.757G > A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting Intron 1 of BCKDHA, which was identified by whole‐genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction‐specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal/preimplantation tests are necessary.

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Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

Cited by 2 publications

References 19 publications

Metabolomics of neurological disorders in India

Metabolomics of neurological disorders in India

Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA: A case report

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