Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects

Ayman W. El-Hattab, Fang Yuan Li, Joseph Shen, Berkley R. Powell, Erawati V. Bawle, Darius J. Adams, Erica Wahl, Joyce A. Kobori, Brett Graham, Fernando Scaglia, Lee Jun Wong

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

BACKGROUND: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency. METHODS: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists. RESULT: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324-1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia. DISCUSSION: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalGenetics in Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Carnitine
Mothers
Newborn Infant
Genes
Neonatal Screening
Inborn Errors Metabolism
Mutation
Pre-Eclampsia
Cardiomyopathies
Systemic carnitine deficiency
Cations
Pregnancy
DNA

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

El-Hattab, Ayman W. ; Li, Fang Yuan ; Shen, Joseph ; Powell, Berkley R. ; Bawle, Erawati V. ; Adams, Darius J. ; Wahl, Erica ; Kobori, Joyce A. ; Graham, Brett ; Scaglia, Fernando ; Wong, Lee Jun. / Maternal systemic primary carnitine deficiency uncovered by newborn screening : Clinical, biochemical, and molecular aspects. In: Genetics in Medicine. 2010 ; Vol. 12, No. 1. pp. 19-24.
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abstract = "BACKGROUND: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency. METHODS: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists. RESULT: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324-1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia. DISCUSSION: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.",
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El-Hattab, AW, Li, FY, Shen, J, Powell, BR, Bawle, EV, Adams, DJ, Wahl, E, Kobori, JA, Graham, B, Scaglia, F & Wong, LJ 2010, 'Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects', Genetics in Medicine, vol. 12, no. 1, pp. 19-24. https://doi.org/10.1097/GIM.0b013e3181c5e6f7

Maternal systemic primary carnitine deficiency uncovered by newborn screening : Clinical, biochemical, and molecular aspects. / El-Hattab, Ayman W.; Li, Fang Yuan; Shen, Joseph; Powell, Berkley R.; Bawle, Erawati V.; Adams, Darius J.; Wahl, Erica; Kobori, Joyce A.; Graham, Brett; Scaglia, Fernando; Wong, Lee Jun.

In: Genetics in Medicine, Vol. 12, No. 1, 01.01.2010, p. 19-24.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Maternal systemic primary carnitine deficiency uncovered by newborn screening

T2 - Clinical, biochemical, and molecular aspects

AU - El-Hattab, Ayman W.

AU - Li, Fang Yuan

AU - Shen, Joseph

AU - Powell, Berkley R.

AU - Bawle, Erawati V.

AU - Adams, Darius J.

AU - Wahl, Erica

AU - Kobori, Joyce A.

AU - Graham, Brett

AU - Scaglia, Fernando

AU - Wong, Lee Jun

PY - 2010/1/1

Y1 - 2010/1/1

N2 - BACKGROUND: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency. METHODS: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists. RESULT: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324-1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia. DISCUSSION: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.

AB - BACKGROUND: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency. METHODS: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists. RESULT: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324-1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia. DISCUSSION: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.

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