Long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency: Identification of a new inborn error of mitochondrial fatty acidβ‐oxidation

Abstract

Fatty acids are a major source of metabolic fuel in man. Both mitochondria and peroxisomes are capable of fatty acid fl-oxidation (Schulz, 1985). It is generally agreed that the oxidation of medium and long chain fatty acids, which are most abundant in our daily diet, takes place predominantly in mitochondria. In contrast, peroxisomal fl-oxidafion is not so important for energy purposes, but catalyses the chainshortening of a distinct set of substrates which includes very long chain fatty acids, certain mono-and polyunsaturated fatty acids and di-and trihydroxycholestanoic acid (see Wanders et al., 1990 for review). The different physiological functions of mitochondrial and peroxisomal fl-oxidation are reflected in the widely differing clinical consequences of defects in mitochondrial and peroxisomal fl-oxidation, respectively. In recent years an increasing number of inherited diseases in man have been recognized in which there is an impairment in mitochondrial fl-oxidation (Vianey-Liaud et al., 1987). In this paper we report the identification of a new inborn error of mitochondfial fi-oxidation at the level of long chain 3-hydroxyacyl-CoA dehydrogenase in a child who presented at 5 months of age with diarrhoea and vomiting, subsequently followed by increasing lethargy which appeared to be associated with hypoketotic hypoglycaemia. MATERIALS AND METHODS Enzyme activity measurementsThe activity of 3-hydroxyacyl-CoA dehydrogenase was measured in homogenates of cultured skin fibroblasts at 37°C by following the decrease in absorbance at 311

Peroxisomal and mitochondrial carnitine acetyltransferases of Saccharomyces cerevisiae are encoded by a single gene.

“…After 15 min, the reactions were terminated by addition of 5 vol ice-cold ethanol. The [14C] (Wanders et al, 1990), succinate dehydrogenase measurements (Munujos et al, 1993) and P-galactosidase colony assay (Fields and Song, 1989). PCR, primer extension and other DNA techniques were carried out as described by Sambrook et al (1989).…”

Necrotizing Enterocolitis and Respiratory Distress Syndrome as First Clinical Presentation of Mitochondrial Trifunctional Protein Deficiency

“…Enzymatic activity measurements in lymphocytes and/or fibroblast were carried out as previously described (Wanders et al 1990(Wanders et al /1992. NBS acylcarnitine profiling was performed as described by Chace et al (2003).…”

“…Hydroxyacyl-CoA dehydrogenase (HAD) activity was measured in homogenates of cultured fibroblasts by observing the decrease in absorbance at 340 nm (Wanders et al 1990). 3-Keto-hexadecanoyl-CoA (C16) and acetoacetyl-CoA (C4) have been used as substrates for LCHAD activity measurements.…”

“…3-Keto-hexadecanoyl-CoA (C16) and acetoacetyl-CoA (C4) have been used as substrates for LCHAD activity measurements. LCHAD shows highest activity with C16 as substrate with virtually no reactivity with C4 as substrate (Wanders 1990;Wanders et al 2010). However, another dehydrogenase -short chain hydroxyaxcyl-CoA dehydrogenase (SCHAD) -has activity with both C16 and C4.…”

“…LCKAT activity was measured in homogenates of cultured fibroblasts by following the decrease in absorbance at 303 nm (Wanders et al 1990). …”