Cargando…

Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography

Isolated long-chain 3-keto-acyl CoA thiolase (LCKAT) deficiency is a rare long-chain fatty acid oxidation disorder caused by mutations in HADHB. LCKAT is part of a multi-enzyme complex called the mitochondrial trifunctional protein (MTP) which catalyzes the last three steps in the long-chain fatty a...

Descripción completa

Detalles Bibliográficos
Autores principales: Veenvliet, Annemarijne R.J., Garrelfs, Mark R., Udink ten Cate, Floris E.A., Ferdinandusse, Sacha, Denis, Simone, Fuchs, Sabine A., Schwantje, Marit, Geurtzen, Rosa, van Wegberg, Annemiek M.J., Huigen, Marleen C.D.G., Kluijtmans, Leo A.J., Wanders, Ronald J.A., Derks, Terry G.J., de Boer, Lonneke, Houtkooper, Riekelt H., de Vries, Maaike C., van Karnebeek, Clara D.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248206/
https://www.ncbi.nlm.nih.gov/pubmed/35782614
http://dx.doi.org/10.1016/j.ymgmr.2022.100873
_version_ 1784739321983533056
author Veenvliet, Annemarijne R.J.
Garrelfs, Mark R.
Udink ten Cate, Floris E.A.
Ferdinandusse, Sacha
Denis, Simone
Fuchs, Sabine A.
Schwantje, Marit
Geurtzen, Rosa
van Wegberg, Annemiek M.J.
Huigen, Marleen C.D.G.
Kluijtmans, Leo A.J.
Wanders, Ronald J.A.
Derks, Terry G.J.
de Boer, Lonneke
Houtkooper, Riekelt H.
de Vries, Maaike C.
van Karnebeek, Clara D.M.
author_facet Veenvliet, Annemarijne R.J.
Garrelfs, Mark R.
Udink ten Cate, Floris E.A.
Ferdinandusse, Sacha
Denis, Simone
Fuchs, Sabine A.
Schwantje, Marit
Geurtzen, Rosa
van Wegberg, Annemiek M.J.
Huigen, Marleen C.D.G.
Kluijtmans, Leo A.J.
Wanders, Ronald J.A.
Derks, Terry G.J.
de Boer, Lonneke
Houtkooper, Riekelt H.
de Vries, Maaike C.
van Karnebeek, Clara D.M.
author_sort Veenvliet, Annemarijne R.J.
collection PubMed
description Isolated long-chain 3-keto-acyl CoA thiolase (LCKAT) deficiency is a rare long-chain fatty acid oxidation disorder caused by mutations in HADHB. LCKAT is part of a multi-enzyme complex called the mitochondrial trifunctional protein (MTP) which catalyzes the last three steps in the long-chain fatty acid oxidation. Until now, only three cases of isolated LCKAT deficiency have been described. All patients developed a severe cardiomyopathy and died before the age of 7 weeks. Here, we describe a newborn with isolated LCKAT deficiency, presenting with neonatal-onset cardiomyopathy, rhabdomyolysis, hypoglycemia and lactic acidosis. Bi-allelic 185G > A (p.Arg62His) and c1292T > C (p.Phe431Ser) mutations were found in HADHB. Enzymatic analysis in both lymphocytes and cultured fibroblasts revealed LCKAT deficiency with a normal long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD, also part of MTP) enzyme activity. Clinically, the patient showed recurrent cardiomyopathy, which was monitored by speckle tracking echocardiography. Subsequent treatment with special low-fat formula, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT) and ketone body therapy in (sodium-D,L-3-hydroxybutyrate) was well tolerated and resulted in improved carnitine profiles and cardiac function. Resveratrol, a natural polyphenol that has been shown to increase fatty acid oxidation, was also considered as a potential treatment option but showed no in vitro benefits in the patient's fibroblasts. Even though our patient deceased at the age of 13 months, early diagnosis and prompt initiation of dietary management with addition of sodium-D,L-3-hydroxybutyrate may have contributed to improved cardiac function and a much longer survival when compared to the previously reported cases of isolated LCKAT-deficiency.
format Online
Article
Text
id pubmed-9248206
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-92482062022-07-02 Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography Veenvliet, Annemarijne R.J. Garrelfs, Mark R. Udink ten Cate, Floris E.A. Ferdinandusse, Sacha Denis, Simone Fuchs, Sabine A. Schwantje, Marit Geurtzen, Rosa van Wegberg, Annemiek M.J. Huigen, Marleen C.D.G. Kluijtmans, Leo A.J. Wanders, Ronald J.A. Derks, Terry G.J. de Boer, Lonneke Houtkooper, Riekelt H. de Vries, Maaike C. van Karnebeek, Clara D.M. Mol Genet Metab Rep Research Paper Isolated long-chain 3-keto-acyl CoA thiolase (LCKAT) deficiency is a rare long-chain fatty acid oxidation disorder caused by mutations in HADHB. LCKAT is part of a multi-enzyme complex called the mitochondrial trifunctional protein (MTP) which catalyzes the last three steps in the long-chain fatty acid oxidation. Until now, only three cases of isolated LCKAT deficiency have been described. All patients developed a severe cardiomyopathy and died before the age of 7 weeks. Here, we describe a newborn with isolated LCKAT deficiency, presenting with neonatal-onset cardiomyopathy, rhabdomyolysis, hypoglycemia and lactic acidosis. Bi-allelic 185G > A (p.Arg62His) and c1292T > C (p.Phe431Ser) mutations were found in HADHB. Enzymatic analysis in both lymphocytes and cultured fibroblasts revealed LCKAT deficiency with a normal long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD, also part of MTP) enzyme activity. Clinically, the patient showed recurrent cardiomyopathy, which was monitored by speckle tracking echocardiography. Subsequent treatment with special low-fat formula, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT) and ketone body therapy in (sodium-D,L-3-hydroxybutyrate) was well tolerated and resulted in improved carnitine profiles and cardiac function. Resveratrol, a natural polyphenol that has been shown to increase fatty acid oxidation, was also considered as a potential treatment option but showed no in vitro benefits in the patient's fibroblasts. Even though our patient deceased at the age of 13 months, early diagnosis and prompt initiation of dietary management with addition of sodium-D,L-3-hydroxybutyrate may have contributed to improved cardiac function and a much longer survival when compared to the previously reported cases of isolated LCKAT-deficiency. Elsevier 2022-05-04 /pmc/articles/PMC9248206/ /pubmed/35782614 http://dx.doi.org/10.1016/j.ymgmr.2022.100873 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Veenvliet, Annemarijne R.J.
Garrelfs, Mark R.
Udink ten Cate, Floris E.A.
Ferdinandusse, Sacha
Denis, Simone
Fuchs, Sabine A.
Schwantje, Marit
Geurtzen, Rosa
van Wegberg, Annemiek M.J.
Huigen, Marleen C.D.G.
Kluijtmans, Leo A.J.
Wanders, Ronald J.A.
Derks, Terry G.J.
de Boer, Lonneke
Houtkooper, Riekelt H.
de Vries, Maaike C.
van Karnebeek, Clara D.M.
Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title_full Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title_fullStr Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title_full_unstemmed Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title_short Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
title_sort neonatal long-chain 3-ketoacyl-coa thiolase deficiency: clinical-biochemical phenotype, sodium-d,l-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248206/
https://www.ncbi.nlm.nih.gov/pubmed/35782614
http://dx.doi.org/10.1016/j.ymgmr.2022.100873
work_keys_str_mv AT veenvlietannemarijnerj neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT garrelfsmarkr neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT udinktencateflorisea neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT ferdinandussesacha neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT denissimone neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT fuchssabinea neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT schwantjemarit neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT geurtzenrosa neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT vanwegbergannemiekmj neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT huigenmarleencdg neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT kluijtmansleoaj neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT wandersronaldja neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT derksterrygj neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT deboerlonneke neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT houtkooperriekelth neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT devriesmaaikec neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography
AT vankarnebeekclaradm neonatallongchain3ketoacylcoathiolasedeficiencyclinicalbiochemicalphenotypesodiumdl3hydroxybutyratetreatmentexperienceandcardiacevaluationusingspeckleechocardiography