Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis

Hwang, Narae; Jang, Ja‐Hyun; Cho, Eun Hae; Choi, Rihwa; Choi, Suk‐Joo; Park, Hyung-Doo

doi:10.1002/mgg3.1838

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…The mother delivered a healthy baby, and the neonate did not show symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth. 14 In Taiwan, a nationwide newborn screening program for isolated methylmalonic acidemia (MMA)/propionic acidemia (PA) in neonatal has shown that patients with MMA mutase type and PA cases are at risk for death and neurodevelopmental disability. The study found that MMA patients have higher AST, ALT, and NH3 values, and lower pH values.…”

Section: Discussionmentioning

confidence: 99%

New-born screening of metabolites with liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry: a metabolic and molecular signatures methyl malonic aciduria with combined oxidative phosphorylation deficiency-10: a rare case report

Subramaniam,

A. T.,

Subramaniam

et al. 2023

Int J Contemp Pediatr

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An uncommon autosomal recessive organic acid disease is malonic aciduria. This disease may be easily identified and included in the NBS programmes by means of the widespread use of tandem mass spectrometry’s in the study of the amino acid/acylcarnitine profile using dried blood spots (DBS) for newborn screening. In Tamil Nadu, we reported the first screened and diagnosed with malonic aciduria by newborn screening (NBS) in early neonatal period. The patient possesses a malonyl-CoA decarboxylase genetic variation not previously described. This disease should be distinguished from a related malonic and methylmalonic aciduria problem. Malonic aciduria's clinical phenomenology varies and pathogenesis is not completely known. The proper treatment regimen, nutritional therapy or frequent follow-up to these individuals are not guided or recommended. The majority of current treatment data is based on a single research or case report.

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Section: Discussionmentioning

confidence: 99%

New-born screening of metabolites with liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry: a metabolic and molecular signatures methyl malonic aciduria with combined oxidative phosphorylation deficiency-10: a rare case report

Subramaniam,

A. T.,

Subramaniam

et al. 2023

Int J Contemp Pediatr

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“…To confirm the biochemical diagnosis, guide management, and provide genetic counseling to families, the underlying genetic defect must be identified ( Forny et al, 2021 ). MMA is highly genetically heterogeneous, and at least 10 disease-related genes have been identified; among them, mutations in MUT (mut type), MMAA (cblA type), MMAB (cblB type), MMACHC (cblC type), MMADHC (cblD type), LMBRD1 (cblF type), ABCD4 (cblJ type), and HCFC1 (cblX type) are the most common ( Hwang et al, 2021 ).…”

Section: Diagnosis Of Mmamentioning

confidence: 99%

“…A clinical cohort study reported that 12 children with cblC defects diagnosed by newborn screening were found to have developmental delays, most of whom presented with hypotonia and nystagmus, while neurodevelopmental assessments suggested that impaired motor development was the most prominent deficiency ( Weisfeld-Adams et al, 2013 ). Late-onset patients may have atypical symptoms such as mental symptoms and cognitive decline ( Hwang et al, 2021 ).…”

Section: Mechanism Of Nervous System Injury and Neurodevelopmental Ch...mentioning

confidence: 99%

Methylmalonic acidemia: Neurodevelopment and neuroimaging

et al. 2023

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Methylmalonic acidemia (MMA) is a genetic disease of abnormal organic acid metabolism, which is one of the important factors affecting the survival rate and quality of life of newborns or infants. Early detection and diagnosis are particularly important. The diagnosis of MMA mainly depends on clinical symptoms, newborn screening, biochemical detection, gene sequencing and neuroimaging diagnosis. The accumulation of methylmalonic acid and other metabolites in the body of patients causes brain tissue damage, which can manifest as various degrees of intellectual disability and severe neurological dysfunction. Neuroimaging examination has important clinical significance in the diagnosis and prognosis of MMA. This review mainly reviews the etiology, pathogenesis, and nervous system development, especially the neuroimaging features of MMA.

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“…ABCD4 is found in lysosomes and participates in the transport of cobalamin (vitamin B12) from lysosomes into the cytosol. It is linked to methylmalonic aciduria and homocystinuria type cblJ (Hwang et al, 2021 ) and is also X-linked to adrenoleukodystrophy (Kawaguchi and Imanaka, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants

Pan,

Tao,

Smorodina

et al. 2024

QRB Discovery

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Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90–54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.

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Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 26 publications

New-born screening of metabolites with liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry: a metabolic and molecular signatures methyl malonic aciduria with combined oxidative phosphorylation deficiency-10: a rare case report

New-born screening of metabolites with liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry: a metabolic and molecular signatures methyl malonic aciduria with combined oxidative phosphorylation deficiency-10: a rare case report

Methylmalonic acidemia: Neurodevelopment and neuroimaging

Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants

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