Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Identification of two new mutations

  title={Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Identification of two new mutations},
  author={Lodewijk Ijlst and Wendy Oostheim and J. P. N. Ruitter and Ronald J.A. Wanders},
  journal={Journal of Inherited Metabolic Disease},
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) is catalysed by the mitochondrial trifunctional protein (MTP), which also contains enoyl-CoA hydratase and 3-ketothiolase activities (Carpenter et al 1992; Uchida et al 1992). The cDNAs encoding the a and β subunits were cloned by Kamijo et al (1994a). Many patients have been described with a defect in this enzyme complex and it appears that in most patients there is an isolated deficiency of the dehydrogenase activity of the MTP. We and others… 

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A new method to identify the G1528C mutation in genomic DNA showing its high frequency (≈90%) and identification of a new mutation (T2198C)

The identification of a point mutation at position 1528 of the cDNA for the α-subunit of mitochondrial trifunctional protein in fibroblasts from LC3HAD-deficient patients of group II is reported and a new mutation is described in a patient heterozygous for the G1528C mutation.

Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency.

Clinical and biochemical data show that patients with LCHAD deficiency can have normal growth and development with appropriate treatment, and low-dose carnitine supplements prevented carnitines deficiency and did not result in increased long-chain hydroxylated acylcarnitines or any specific toxicity.

Twin brothers, one of whom first presented with gastrointestinal perforation, with long chain-3-hydroxyacyl-CoA dehydrogenase deficiency and novel compound heterozygous mutations in the HADHA gene: case report and literature review

Twin brothers diagnosed with LCHADD who harboured the same novel compound heterozygous mutations in the HADHA gene were examined, and one of them presented with gastrointestinal perforation, a rarely reported manifestation.

Acute Fatty Liver of Pregnancy

Both parents and the infant should be tested for deficiencies of the mitochondrial fatty acid oxidation, especially for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, as many cases of AFLP are related to disruption of this physiological enzymatic pathway.

Acute fatty liver of pregnancy : a retrospective analysis of 13 cases

Giving intravenous albumin or in addition to dopamine and terlipressin were effective in the treatment of hepatorenal syndrome and also helpful to the recovery of liver function.

Acute fatty liver of pregnancy.

  • H. KoE. Yoshida
  • Medicine
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie
  • 2006
Supportive care and expeditious delivery are essential to optimal maternal-fetal outcomes and remain as the mainstay treatment for AFLP.

Acute pancreatitis in a pregnant woman with acute fatty liver dystrophy. A case report.

The case of a 26-year-old primigravida, at 25 weeks' gestation, who developed acute fatty liver of pregnancy and acute pancreatitis after an acute viral upper respiratory tract infection, with an unfavorable evolution to death.

Acute Kidney Injury in Pregnancy

Pregnancy related AKI (PRAKI) is on the decline from 14.5% reported in 1987 to 4.3% in 2005 in India.



Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: high frequency of the G1528C mutation with no apparent correlation with the clinical phenotype

Enzyme activity measurements have shown that in these patients long-chain 3-hydroxyacyl-CoA dehydrogenase is deficient to the same extent as in group I patients, whereas long- chain enoyl- CoA hydratase and long- Chain 3-ketothiolase are partially deficient at 78% and 59%, respectively, of control levels.

Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.

It is shown that the G1528C mutation is directly responsible for the loss of LCHAD activity and the gene encoding the alpha subunit of MTP is located on chromosome 2p24.1-23.3.

Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein.

The authors cloned, sequenced, and expressed the following cDNAs for the alpha- and beta-subunits of human trifunctional protein and yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity.

Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients.

In both patients, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is caused by an abnormality in the trifunctional protein, even though there is a heterogeneity in both patients.

Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.

Long-chain-3-hydroxyacyl-CoA dehydrogenase

The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.

It is demonstrated that mutations in the LCHAD domain of the trifunctional protein alpha subunit in affected offspring are associated with maternal acute fatty liver of pregnancy and the initial delineation of the molecular basis of isolated LCHad deficiency is delineated.

Sex and the single DAX1: too little is bad, but can we have too much?

  • E. McCabe
  • Biology
    The Journal of clinical investigation
  • 1996
The results indicate that the relationship between the hypothalamus and pituitary in male sexual development may be more complex than previously appreciated, and highlight significant issues regarding the role of the DAX1 gene product in female sexual differentiation.