DOI: 10.1373/clinchem.2005.062000. Isolated Mitochondrial Long-Chain Ketoacyl-CoA Thiolase Deficiency Resulting from Mutations in the HADHB Gene

Isolated Mitochondrial Long-Chain Ketoacyl-CoA Thiolase Deficiency Resulting from Mutations in the HADHB Gene

10.1373/clinchem.2005.062000

Crossref journal-article

Oxford University Press (OUP)

Clinical Chemistry (286)

Abstract

AbstractBackground: The human mitochondrial trifunctional protein (MTP) complex is composed of 4 hydroacyl-CoA dehydrogenase-α (HADHA) and 4 hydroacyl-CoA dehydrogenase-β (HADHB) subunits, which catalyze the last 3 steps in the fatty acid β-oxidation spiral of long-chain fatty acids. The HADHB gene encodes long-chain ketoacyl-CoA thiolase (LCTH) activity, whereas the HADHA gene contains the information for the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) functions. At present, 2 different biochemical phenotypes of defects in the mitochondrial trifunctional protein complex are known: isolated LCHAD deficiency and generalized MTP deficiency, with decreased activities of all 3 enzymes. Isolated LCTH deficiency with mutations in the HADHB gene has not been reported.Patient and Results: We report a male newborn who presented with lactic acidosis, pulmonary edema, and cardiomyopathy leading to acute heart failure and death at the age of 6 weeks. Routine newborn screening by tandem mass spectrometry showed increased concentrations of the acylcarnitines tetradecenoylcarnitine, hexadecenoylcarnitine, hydroxypalmitoylcarnitine, and hydroxyoctadecenoylcarnitine, suggesting LCHAD deficiency or complete MTP deficiency. Enzyme investigations revealed very low LCTH (4% of normal) and normal LCHAD activities, whereas molecular analysis showed compound heterozygosity for 185G&gt;A (R62H) and 1292T&gt;C (F431S) mutations in the HADHB gene.Conclusion: We describe the first case of isolated LCTH deficiency based on a mutation in the HADHB gene.

Bibliography

Das, A. M., Illsinger, S., LuÌcke, T., Hartmann, H., Ruiter, J. P., Steuerwald, U., Waterham, H. R., Duran, M., & Wanders, R. J. (2006). Isolated Mitochondrial Long-Chain Ketoacyl-CoA Thiolase Deficiency Resulting from Mutations in the HADHB Gene. Clinical Chemistry, 52(3), 530â534.

Authors 9

Anibh M Das (first)
Sabine Illsinger (first)
Thomas Lücke (first)
Hans Hartmann (first)
Jos PN Ruiter (first)
Ulrike Steuerwald (first)
Hans R Waterham (first)
Marinus Duran (first)
Ronald JA Wanders (first)

References 22 Referenced 61

Dates

Type	When
Created	19 years, 7 months ago (Jan. 19, 2006, 8:39 p.m.)
Deposited	4 years, 1 month ago (July 22, 2021, 5:47 p.m.)
Indexed	1 week ago (Aug. 29, 2025, 6:35 a.m.)
Issued	19 years, 6 months ago (March 1, 2006)
Published	19 years, 6 months ago (March 1, 2006)
Published Online	19 years, 6 months ago (March 1, 2006)
Published Print	19 years, 6 months ago (March 1, 2006)

Funders 0

None

BibTeX

@article{Das_2006, title={Isolated Mitochondrial Long-Chain Ketoacyl-CoA Thiolase Deficiency Resulting from Mutations in the HADHB Gene}, volume={52}, ISSN={1530-8561}, url={http://dx.doi.org/10.1373/clinchem.2005.062000}, DOI={10.1373/clinchem.2005.062000}, number={3}, journal={Clinical Chemistry}, publisher={Oxford University Press (OUP)}, author={Das, Anibh M and Illsinger, Sabine and Lücke, Thomas and Hartmann, Hans and Ruiter, Jos PN and Steuerwald, Ulrike and Waterham, Hans R and Duran, Marinus and Wanders, Ronald JA}, year={2006}, month=mar, pages={530–534} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>Background: The human mitochondrial trifunctional protein (MTP) complex is composed of 4 hydroacyl-CoA dehydrogenase-\u03b1 (HADHA) and 4 hydroacyl-CoA dehydrogenase-\u03b2 (HADHB) subunits, which catalyze the last 3 steps in the fatty acid \u03b2-oxidation spiral of long-chain fatty acids. The HADHB gene encodes long-chain ketoacyl-CoA thiolase (LCTH) activity, whereas the HADHA gene contains the information for the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) functions. At present, 2 different biochemical phenotypes of defects in the mitochondrial trifunctional protein complex are known: isolated LCHAD deficiency and generalized MTP deficiency, with decreased activities of all 3 enzymes. Isolated LCTH deficiency with mutations in the HADHB gene has not been reported.</jats:p><jats:p>Patient and Results: We report a male newborn who presented with lactic acidosis, pulmonary edema, and cardiomyopathy leading to acute heart failure and death at the age of 6 weeks. Routine newborn screening by tandem mass spectrometry showed increased concentrations of the acylcarnitines tetradecenoylcarnitine, hexadecenoylcarnitine, hydroxypalmitoylcarnitine, and hydroxyoctadecenoylcarnitine, suggesting LCHAD deficiency or complete MTP deficiency. Enzyme investigations revealed very low LCTH (4% of normal) and normal LCHAD activities, whereas molecular analysis showed compound heterozygosity for 185G&amp;gt;A (R62H) and 1292T&amp;gt;C (F431S) mutations in the HADHB gene.</jats:p><jats:p>Conclusion: We describe the first case of isolated LCTH deficiency based on a mutation in the HADHB gene.</jats:p>",
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