Impact of selected inborn errors of metabolism on prenatal and neonatal development

Illsinger, Sabine

doi:10.1002/iub.336

Cited by 39 publications

(26 citation statements)

References 101 publications

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“…Brain malformations in NKH include ventriculomegaly, dysgenetic corpus callosum, and posterior fossa cysts [3, 4]. Dandy–Walker malformation is a congenital disorder that involves the cerebellar vermis and fourth ventricle.…”

Section: Discussionmentioning

confidence: 99%

“…An increased lactate peak can be observed and may reflect anaerobic glycolysis of brain tissue, probably caused by hypoxia [1]. Diagnosis is made by showing high CSF and plasma glycine levels [3]. Most patients die during the neonatal period [2, 4].…”

Section: Discussionmentioning

confidence: 99%

“…The recognition of NKH leads not only to immediate care of the patient, but also to genetic counseling to prevent recurrences in further pregnancies [3]. …”

Section: Discussionmentioning

confidence: 99%

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A rare inborn error of metabolism associated with a Dandy–Walker malformation

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A rare inborn error of metabolism associated with a Dandy–Walker malformation

et al. 2012

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“…Mammalian development is characterized by a programmed succession of different developmental stages, with the activation and suppression of various metabolic pathways, and whose regulation during fetal development might not only be important for early development but may also have implications for health and disease in adulthood (Illsinger and Das, ).…”

Section: Discussionmentioning

confidence: 99%

Classic Galactosemia: Study on the Late Prenatal Development of GALT Specific Activity in a Sheep Model

Coelho

Bierau

Lindhout

et al. 2017

The Anatomical Record

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Classic galactosemia results from deficient activity of galactose-1-phosphate uridylyltransferase (GALT), a key enzyme of galactose metabolism. Despite early diagnosis and early postnatal therapeutic intervention, patients still develop neurologic and fertility impairments. Prenatal developmental toxicity has been hypothesized as a determinant factor of disease. In order to shed light on the importance of prenatal GALT activity, several studies have examined GALT activity throughout development. GALT was shown to increase with gestational age in 7-28 weeks human fetuses; later stages were not investigated. Prenatal studies in animals focused exclusively on brain and hepatic GALT activity. In this study, we aim to examine GALT specific activity in late prenatal and adult stages, using a sheep model. Galactosemia acute target-organs-liver, small intestine and kidney-had the highest late prenatal activity, whereas the chronic target-organs-brain and ovary-did not exhibit a noticeable pre- or postnatal different activity compared with nontarget organs. This is the first study on GALT specific activity in the late prenatal stage for a wide variety of organs. Our findings suggest that GALT activity cannot be the sole pathogenic factor accounting for galactosemia long-term complications, and that some organs/cells might have a greater susceptibility to galactose toxicity. Anat Rec, 300:1570-1575, 2017. © 2017 Wiley Periodicals, Inc.

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“…Until now, however, no published work has reported a direct comparison of cytosolic ATP concentration ([ATP]c) levels in postnatal vs. embryonic cultured neurons. Such a comparison is timely and relevant, in view of the widespread use of both types of cultures and considering the growing body of evidence that the cascade of molecular and cellular modifications occurring at birth strongly affects bioenergetics of neurons in neonatal brain (Lust et al, 2003; Illsinger and Das, 2010). …”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of cytosolic and mitochondrial ATP synthesis in embryonic and postnatal hippocampal neuronal cultures

Surin¹,

Khiroug²,

Горбачева³

et al. 2013

Front. Mol. Neurosci.

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ATP in neurons is commonly believed to be synthesized mostly by mitochondria via oxidative phosphorylation. Neuronal mitochondria have been studied primarily in culture, i.e., in neurons isolated either from embryos or from neonatal pups. Although it is generally assumed that both embryonic and postnatal cultured neurons derive their ATP from mitochondrial oxidative phosphorylation, this has never been tested experimentally. We expressed the FRET-based ATP sensor AT1.03 in cultured hippocampal neurons isolated either from E17 to E18 rat embryos or from P1 to P2 rat pups and monitored [ATP]c simultaneously with mitochondrial membrane potential (ΔΨm; TMRM) and NAD(P)H autofluorescence. In embryonic neurons, transient glucose deprivation induced a near-complete decrease in [ATP]c, which was partially reversible and was accelerated by inhibition of glycolysis with 2-deoxyglucose. In the absence of glucose, pyruvate did not cause any significant increase in [ATP]c in 84% of embryonic neurons, and inhibition of mitochondrial ATP synthase with oligomycin failed to decrease [ATP]c. Moreover, ΔΨm was significantly reduced by oligomycin, indicating that mitochondria acted as consumers rather than producers of ATP in embryonic neurons. In sharp contrast, in postnatal neurons pyruvate added during glucose deprivation significantly increased [ATP]c (by 54 ± 8%), whereas oligomycin induced a sharp decline in [ATP]c and increased ΔΨm. These signs of oxidative phosphorylation were observed in all tested P1–P2 neurons. Measurement of ΔΨm with the potential-sensitive probe JC-1 revealed that neuronal mitochondrial membrane potential was significantly reduced in embryonic cultures compared to the postnatal ones, possibly due to increased proton permeability of inner mitochondrial membrane. We conclude that, in embryonic, but not postnatal neuronal cultures, ATP synthesis is predominantly glycolytic and the oxidative phosphorylation-mediated synthesis of ATP by mitochondrial F1Fo-ATPase is insignificant.

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Impact of selected inborn errors of metabolism on prenatal and neonatal development

Cited by 39 publications

References 101 publications

A rare inborn error of metabolism associated with a Dandy–Walker malformation

A rare inborn error of metabolism associated with a Dandy–Walker malformation

Classic Galactosemia: Study on the Late Prenatal Development of GALT Specific Activity in a Sheep Model

Comparative analysis of cytosolic and mitochondrial ATP synthesis in embryonic and postnatal hippocampal neuronal cultures

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