Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency

Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHS) deficiency is an ultra-rare inborn error of ketone body synthesis that is caused by biallelic mutations in HMGCS2. The manifestations of mHS deficiency can include hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopath...

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Main Authors: Mayowa A. Osundiji, Alicia Chen, Joseph D. Farris, Radhika Dhamija
Format: Article
Language:English
Published: American College of Physicians 2025-08-01
Series:Annals of Internal Medicine: Clinical Cases
Online Access:https://www.acpjournals.org/doi/10.7326/aimcc.2025.0080
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author Mayowa A. Osundiji
Alicia Chen
Joseph D. Farris
Radhika Dhamija
author_facet Mayowa A. Osundiji
Alicia Chen
Joseph D. Farris
Radhika Dhamija
author_sort Mayowa A. Osundiji
collection DOAJ
description Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHS) deficiency is an ultra-rare inborn error of ketone body synthesis that is caused by biallelic mutations in HMGCS2. The manifestations of mHS deficiency can include hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, hyperammonemia, and hepatomegaly. Here, we report a case of movement disorder following hypoglycemic encephalopathy involving the basal ganglia in a patient with mHS deficiency. Exome sequencing showed novel compound heterozygous variants in HMGCS2, a partial gene deletion (classified as pathogenic) and c.704T>A (p.M235K) variant that was deemed to be likely pathogenic. Our findings suggest that mHS deficiency can result in basal ganglia injury and movement disorder.
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institution Kabale University
issn 2767-7664
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publishDate 2025-08-01
publisher American College of Physicians
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series Annals of Internal Medicine: Clinical Cases
spelling doaj-art-2a907f59bd8e47f1a6ab7d23f08ad70b2025-08-20T03:39:31ZengAmerican College of PhysiciansAnnals of Internal Medicine: Clinical Cases2767-76642025-08-014810.7326/aimcc.2025.0080Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) DeficiencyMayowa A. Osundiji0Alicia Chen1Joseph D. Farris2Radhika Dhamija31Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota3Department of Radiology, Mayo Clinic, Scottsdale, Arizona4Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota1Department of Clinical Genomics, Mayo Clinic, Rochester, MinnesotaMitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHS) deficiency is an ultra-rare inborn error of ketone body synthesis that is caused by biallelic mutations in HMGCS2. The manifestations of mHS deficiency can include hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, hyperammonemia, and hepatomegaly. Here, we report a case of movement disorder following hypoglycemic encephalopathy involving the basal ganglia in a patient with mHS deficiency. Exome sequencing showed novel compound heterozygous variants in HMGCS2, a partial gene deletion (classified as pathogenic) and c.704T>A (p.M235K) variant that was deemed to be likely pathogenic. Our findings suggest that mHS deficiency can result in basal ganglia injury and movement disorder.https://www.acpjournals.org/doi/10.7326/aimcc.2025.0080
spellingShingle Mayowa A. Osundiji
Alicia Chen
Joseph D. Farris
Radhika Dhamija
Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
Annals of Internal Medicine: Clinical Cases
title Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
title_full Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
title_fullStr Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
title_full_unstemmed Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
title_short Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency
title_sort movement disorder following hypoglycemic encephalopathy in mitochondrial 3 hydroxy 3 methylglutaryl coa synthase 2 mhs deficiency
url https://www.acpjournals.org/doi/10.7326/aimcc.2025.0080
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AT josephdfarris movementdisorderfollowinghypoglycemicencephalopathyinmitochondrial3hydroxy3methylglutarylcoasynthase2mhsdeficiency
AT radhikadhamija movementdisorderfollowinghypoglycemicencephalopathyinmitochondrial3hydroxy3methylglutarylcoasynthase2mhsdeficiency