Clinical, biochemical and molecular characteristics of malonyl-CoA decarboxylase deficiency and long-term follow-up of nine patients

Chapel-Crespo, Cristel C.; Gavrilov, Dimitar; Sowa, Mary; Myers, Jessica A.; Day-Salvatore, Debra-Lynn; Lynn, Haley; Regier, Debra S.; Starin, Danielle; Steenari, Maija; Schoonderwoerd, Kees; Abdenur, José E.

doi:10.1016/j.ymgme.2019.07.015

Cited by 9 publications

(11 citation statements)

References 36 publications

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“…It is also associated with carnitine-acylcarnitine translocase deficiency, malonyl-Coa decarboxylase deficiency. Moreover, adipic acid is also found to be associated with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, carnitine-acylcarnitine translocase deficiency, malonyl-Coa decarboxylase deficiency, and medium Chain acyl-CoA dehydrogenase deficiency [ 43 ]. Adipic acid is also a microbial metabolite found in Escherichia [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Chand¹,

Majid²,

Ahmed³

et al. 2022

BMC Neurol

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Background Diagnosis of autism spectrum disorder (ASD) is generally made phenotypically and the hunt for ASD-biomarkers continues. The purpose of this study was to compare urine organic acids profiles of ASD versus typically developing (TD) children to identify potential biomarkers for diagnosis and exploration of ASD etiology. Methods This case control study was performed in the Department of Pathology and Laboratory Medicine in collaboration with the Department of Pediatrics and Child Health, Aga Khan University, Pakistan. Midstream urine was collected in the first half of the day time before noon from the children with ASD diagnosed by a pediatric neurologist based on DSM-5 criteria and TD healthy controls from August 2019 to June 2021. The urine organic acids were analyzed by Gas Chromatography-Mass Spectrometry. To identify potential biomarkers for ASD canonical linear discriminant analysis was carried out for the organic acids, quantified in comparison to an internal standard. Results A total of 85 subjects were enrolled in the current study. The mean age of the ASD (n = 65) and TD groups (n = 20) was 4.5 ± 2.3 and 6.4 ± 2.2 years respectively with 72.3% males in the ASD group and 50% males in the TD group. Parental consanguinity was 47.7 and 30% in ASD and TD groups, respectively. The common clinical signs noted in children with ASD were developmental delay (70.8%), delayed language skills (66.2%), and inability to articulate sentences (56.9%). Discriminant analysis showed that 3-hydroxyisovalericc, homovanillic acid, adipic acid, suberic acid, and indole acetic were significantly different between ASD and TD groups. The biochemical classification results reveal that 88.2% of cases were classified correctly into ASD& TD groups based on the urine organic acid profiles. Conclusion 3-hydroxy isovaleric acid, homovanillic acid, adipic acid, suberic acid, and indole acetic were good discriminators between the two groups. The discovered potential biomarkers could be valuable for future research in children with ASD.

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Section: Discussionmentioning

confidence: 99%

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Chand¹,

Majid²,

Ahmed³

et al. 2022

BMC Neurol

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“…To the best of our knowledge, 52 patients have been described in the literature so far, in 26 articles or abstracts [ 10 , 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The most common symptoms described in those patients are developmental delay (77%, n = 36 out of 47 patients) and cardiomyopathy (63%, n = 24 out of 38) ( Supplementary Table S1 , Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Acute manifestations included metabolic acidosis (in 18 patients out of 29, or 62%) and hypoglycemic episodes (16 out of 30, or 53%). Newborn screening (NBS) was performed in 14 cases, and the diagnosis was made in 13 of them [ 12 , 21 , 23 , 24 , 29 , 30 ]. Outside of patients diagnosed through NBS, diagnostic delays ranged from a few days to more than 10 years.…”

Section: Resultsmentioning

confidence: 99%

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Heterogenous Clinical Landscape in a Consanguineous Malonic Aciduria Family

Snanoudj

Torre

Sudrié-Arnaud

et al. 2021

IJMS

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Malonic aciduria is an extremely rare inborn error of metabolism due to malonyl-CoA decarboxylase deficiency. This enzyme is encoded by the MLYCD (Malonyl-CoA Decarboxylase) gene, and the disease has an autosomal recessive inheritance. Malonic aciduria is characterized by systemic clinical involvement, including neurologic and digestive symptoms, metabolic acidosis, hypoglycemia, failure to thrive, seizures, developmental delay, and cardiomyopathy. We describe here two index cases belonging to the same family that, despite an identical genotype, present very different clinical pictures. The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. The second case, the cousin of the first patient in a consanguineous family, showed later symptoms, mainly with developmental delay. Both patients showed high levels of malonylcarnitine on acylcarnitine profiles and malonic acid on urinary organic acid chromatographies. The same homozygous pathogenic variant was identified, c.346C > T; p. (Gln116*). We also provide a comprehensive literature review of reported cases. A review of the literature yielded 52 cases described since 1984. The most common signs were developmental delay and cardiomyopathy. Increased levels of malonic acid and malonylcarnitine were constant. Presentations ranged from neonatal death to patients surviving past adolescence. These two cases and reported patients in the literature highlight the inter- and intrafamilial variability of malonic aciduria.

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“…[20][21][22]40 The variant was not previously reported in the clinical literature, and many of the other reported pathogenic variants in this gene are putative loss of function. [41][42][43][44] Importantly, this infant was born prematurely at 23 weeks gestation and required several repeat newborn screens due to inconclusive findings prior to eventual confirmation of malonyl-CoA decarboxylase deficiency at 7 weeks of age. It is worth noting that a ClinVar 20 entry is available for this variant (ClinVar: VCV000432061.2) with a ''likely pathogenic'' interpretation.…”

Section: Metabolic Cohortmentioning

confidence: 99%

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project

Roman

Crowley

Roche

et al. 2020

The American Journal of Human Genetics

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Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 ($18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.

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Clinical, biochemical and molecular characteristics of malonyl-CoA decarboxylase deficiency and long-term follow-up of nine patients

Cited by 9 publications

References 36 publications

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Heterogenous Clinical Landscape in a Consanguineous Malonic Aciduria Family

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project

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