Maternal 3-methylcrotonyl-coenzyme A carboxylase deficiency with elevated 3-hydroxyisovalerylcarnitine in breast milk

Cho, Kyung Lae; Kim, Yeo Jin; Yang, Song; Kim, Gu Hwan; Lee, Jun Hwa

doi:10.3345/kjp.2016.59.11.s41

Cited by 4 publications

(3 citation statements)

References 10 publications

(16 reference statements)

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“…In fact, the detection of maternal deficiencies is now well recognized as a complicating factor in MS/MS NBS, primarily because most maternal defects may present without major symptoms [Ref]. Interestingly, NBS findings showed that newborns with decreased levels of free carnitine were in some cases associated with maternal primary carnitine defect [8,[20][21][22] and in some other cases, with maternal glutaricacidemia type I [20,23]; newborns with increased levels of 3-hydroxyisovalerylcarnitineassociated were sometimes associated with asymptomatic mothers with 3-methylcrotonyl-CoA carboxylase deficiency [8,15,20,24,25]; and newborns with elevated values for phenylalanine with mothers affected by undiagnosed mild hyperphenylalaninemia [8]. All the aforementioned cases highlight the importance of follow-up testing of the mother [15].…”

Section: Discussionmentioning

confidence: 99%

A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy

Rossi

Cicalini

Rizzo

et al. 2020

IJERPH

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Methylmalonic Acidurias (MMAs) are a group of inborn errors of metabolism (IEMs), specifically of propionate catabolism characterized by gastrointestinal and neurometabolic manifestations resulting from a deficiency in the function of methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase, and cobalamin metabolism. In Expanded Newborn Screening (NBS), increased levels of propionylcarnitine (C3) and/or of its ratios by MS/MS analysis of dried blood spots (DBS) samples are suggestive for either Propionic Acidemia or MMAs. C3 elevation is not considered a specific marker for these disorders, resulting in high false-positive rates. The use of analyte ratios improves specificity, but it still cannot resolve the diagnostic issue. Second-tier testing are strongly recommended as confirmation of primary NBS results and for a differential diagnosis. LC-MS/MS analysis allows the quantification of more specific markers of the disorder. Here, we report the case of a newborn with a suspected MMA at Expanded NBS and at second-tier test. Given the urgent situation, in-depth diagnostic investigations were performed. Further investigations surprisingly revealed a Vitamin B12 deficiency due to a maternal malnutrition during pregnancy. This case emphasized that metabolic alterations at NBS may not only be influenced by genome and related to IEMs, but also to external factors and to maternal conditions.

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Section: Discussionmentioning

confidence: 99%

A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy

Rossi

Cicalini

Rizzo

et al. 2020

IJERPH

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“…Symptoms such as vomiting, ketosis, poor oral intake, irritability, lethargy and hypotonia were reported in up to 15% of patients, but the majority (92.5%) of subjects showed completely appropriate age-matched development [15]. In some cases, healthy, affected mothers have been identified through their children's newborn screenings; and C5-OH is known to be elevated in an affected mother's breast milk [16]. An Israeli study described a group of 36 individuals initially identified by a newborn screening program as possessing isolated 3-MCC deficiency; subsequent testing revealed that 20 of those cases were maternal-the infants lacked the disease but had metabolic profiles reflecting those of their affected mothers.…”

Section: Discussionmentioning

confidence: 99%

Novel heterozygous MCCC1 mutations identified in a patient with 3-methylcrotonyl-coenzyme A carboxylase deficiency

et al. 2017

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JGM 3-methylcrotonyl-CoA accumulates and is eventually converted into 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, which are typically elevated in this disease. MCCC2 mutations were reported to be 1.7 times more common than MCCC1 mutations, as found in a cohort study of 53 newborns [3]. Of the genetic mutations reported in Korean patients, 75% have been found within MCCC2 [4,5]. Infants carrying a mutation identified by neonatal screening usually appear to be asymptomatic and remain healthy. However, some patients are reported to present with hypotonia, encephalopathy, seizure, failure to thrive, cardiomyopathy, and late onset severe metabolic decompensation with metabolic acidosis and hypoglycemia [1,[6][7][8][9].In this report, we present the clinical characteristics, laboratory findings and molecular analysis of a patient possessing novel heterozygous mutations of MCCC1.Isolated 3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder affecting leucine metabolism; it is one of the most common inborn metabolic diseases detected in newborn screening. Mutations in the genes MCCC1 or MCCC2 cause a defect in the enzyme 3-methylcrotonyl-CoA carboxylase, with MCCC2 mutations being the form predominantly reported in Korea. The majority of infants identified by neonatal screening usually appear to be asymptomatic and remain healthy; however, some patients have been reported to exhibit mild to severe metabolic decompensation and neurologic manifestations. Here we report the clinical features of a patient with asymptomatic 3-methylcrotonyl-CoA carboxylase deficiency and novel heterozygous MCCC1 mutations.

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“…In addition, other markers revealed by NS screening, aid in diagnosis of maternal metabolic disorders. These include vitamin B12 deficiency, 3-MCC deficiency, and carnitine uptake deficiency (CUD) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Neonatal Screening on Tandem Mass Spectrometry as a Powerful Tool for the Reassessment of the Prevalence of Underestimated Diseases in Newborns and Their Family Members: A Focus on Short Chain Acyl-CoA Dehydrogenase Deficiency

Messina¹,

Arena²,

Fiumara³

et al. 2020

IJNS

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Early detection of disabling diseases, prior to clinical manifestations, is the primary goal of newborn screening (NS). Indeed, the required number of core and secondary conditions selected for screening panels is increasing in many countries. Furthermore, newborn screening can lead to diagnosis of maternal diseases such as vitamin B12 deficiency or 3-MethylcrotonylCoA-carboxylase deficiency (3MCC). NS became mandatory in Sicily in December 2017. Here we report NS data collected between December 2017 and April 2020. Our results show that tandem mass spectrometry is a powerful tool for discovery of underestimated disease in newborns and their family members. Our panel included short chain acyl-CoA dehydrogenase deficiency (SCADD). Here, we report that results of our investigation led to reassessment of SCADD prevalence in our population. The infant and adult patients diagnosed in our study had previously not shown overt symptoms.

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Maternal 3-methylcrotonyl-coenzyme A carboxylase deficiency with elevated 3-hydroxyisovalerylcarnitine in breast milk

Cited by 4 publications

References 10 publications

A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy

A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy

Novel heterozygous MCCC1 mutations identified in a patient with 3-methylcrotonyl-coenzyme A carboxylase deficiency

Neonatal Screening on Tandem Mass Spectrometry as a Powerful Tool for the Reassessment of the Prevalence of Underestimated Diseases in Newborns and Their Family Members: A Focus on Short Chain Acyl-CoA Dehydrogenase Deficiency

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