Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency

Koning, Tom de; Klomp, L.E.O.W.J.; Oppen, Acc van; Beemer, F. A.; Dorland, L.; Berg, Iet van den; Berger, Ruud

doi:10.1016/s0140-6736(04)17596-x

Cited by 127 publications

(72 citation statements)

References 6 publications

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“…KO-MEFs can proliferate in the presence of L-Ser, but their proliferation is suppressed when deprived of L-Ser. 4 Unlike KO-MEFs, the proliferation of WT-MEFs and HeLa cells was not affected by the absence of L-Ser in the culture medium (data not shown).…”

Section: Higher Ratio Of L-ala To L-ser Promoted Doxsl Biosynthesis Imentioning

confidence: 87%

“…Humans with mutated PHGDH have lower levels of free L-Ser in the plasma and in cerebrospinal fluid. These L-Ser-deficient patients exhibit severe neurological symptoms, including congenital microcephaly, psychomotor retardation, and intractable seizures (3)(4)(5). In addition to these data from humans with PHGDH deficiency, our in vivo study demonstrated that conventional Phgdh knock-out (KO) mice display severe consequences of embryonic development, such as brain malformation with overall growth retardation, and die after embryonic day 13.5 (6 -8).…”

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confidence: 99%

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l-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation

Esaki

Sayano

Sonoda³

et al. 2015

Journal of Biological Chemistry

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Background: L-Serine deficiency affects sphingolipid homeostasis. Results: Reduced L-serine promotes the accumulation of 1-deoxysphingolipids and the formation of lipid bodies. Conclusion: Diminished capacity for L-serine synthesis leads to a higher L-alanine to L-serine ratio and elicits the synthesis of 1-deoxysphingolipids and lipid body formation. Significance: 1-Deoxysphingolipids occur in certain disease conditions characterized by a metabolic imbalance between L-alanine and L-serine.

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Section: Higher Ratio Of L-ala To L-ser Promoted Doxsl Biosynthesis Imentioning

confidence: 87%

mentioning

confidence: 99%

l-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation

Esaki

Sayano

Sonoda³

et al. 2015

Journal of Biological Chemistry

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“…Similarly, activity loss of PHGDH in SSP in the brain, which causes low serine and glycine levels, and affects neuronal function, is reversed by serine supplementation 55 . The toxicity and the dosage of serine during its uptake through diet have been previously studied.…”

Section: Discussionmentioning

confidence: 99%

Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease

et al. 2014

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Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis.

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“…Besides PDS, there are at least three other autosomal recessively inherited metabolic disorders that are good candidates for antenatal treatment. In 3-phosphoglycerate-dehydrogenase deficiency (a disorder of serine biosynthesis), supplementation of L-serine has been successful [13]. Vitamin B12-responsive methylmalonic aciduria can be treated by supplementation of the mother with high doses of vitamin B12 [1].…”

Section: Discussionmentioning

confidence: 99%

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

et al. 2009

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Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.

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Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency

Cited by 127 publications

References 6 publications

l-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation

l-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation

Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

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