Implications of Maple Syrup Urine Disease in Newborns

Harris-Haman, Pamela; Brown, Lenora; Massey, Susan Christine; Ramamoorthy, Sivaranjani

doi:10.1016/j.nwh.2017.04.009

Cited by 5 publications

(2 citation statements)

References 7 publications

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“…Other genetic and metabolic diseases are routinely tested in newborn infants, although their frequencies are much lower compared to the prevalence that we report herein for TNZD mutations. A few examples include screening tests which are performed using blood drop from the newborn infant for the detection of phenylketonuria which occurs with a prevalence of 1 in 10 000‐15 000 newborns in the USA, maple syrup urine disease which is estimated to occur with a prevalence of 1 in 185 000 infants worldwide, and propionic acidemia which affects ~1 in 100 000 individuals in the USA …”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we previously emphasized the importance of the early diagnosis of TNZD in order to prevent mild and severe zinc deficiency in infants. 1,20 which is estimated to occur with a prevalence of 1 in 185 000 infants worldwide, 50,51 and propionic acidemia which affects~1 in 100 000 individuals in the USA. [52][53][54] The ExAC database that we used herein is ideal for estimating the prevalence of TNZD risk, as mothers harbouring inactivating ZnT2 mutations which are not associated with any other related disorder, were included in this database which represents exome sequences of healthy individuals of diverse ethnicity.…”

Section: Discussionmentioning

confidence: 99%

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High proportion of transient neonatal zinc deficiency causing alleles in the general population

Golan

Lehvy

Horev

et al. 2018

J Cellular Molecular Medi

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Loss of function (LoF) mutations in the zinc transporter SLC30A2/ZnT2 result in impaired zinc secretion into breast milk consequently causing transient neonatal zinc deficiency (TNZD) in exclusively breastfed infants. However, the frequency of TNZD causing alleles in the general population is yet unknown. Herein, we investigated 115 missense SLC30A2/ZnT2 mutations from the ExAC database, equally distributed in the entire coding region, harboured in 668 alleles in 60 706 healthy individuals of diverse ethnicity. To estimate the frequency of LoF SLC30A2/ZnT2 mutations in the general population, we used bioinformatics tools to predict the potential impact of these mutations on ZnT2 functionality, and corroborated these predictions by a zinc transport assay in human MCF‐7 cells. We found 14 missense mutations that were markedly deleterious to zinc transport. Together with two conspicuous LoF mutations in the ExAC database, 26 SLC30A2/ZnT2 alleles harboured deleterious mutations, suggesting that at least 1 in 2334 newborn infants are at risk to develop TNZD. This high frequency of TNZD mutations combined with the World Health Organization‐promoted increase in the rate of exclusive breastfeeding highlights the importance of genetic screening for inactivating SLC30A2/ZnT2 mutations in the general population for the early diagnosis and prevention of TNZD.

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Section: Discussionmentioning

confidence: 99%