Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine
Abstract Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by SLC33A1 mutations, a gene coding for the acetyl‐CoA transporter‐1 (AT‐1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinica...
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Wiley
2024-11-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12439 |
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| author | Katarina Šikić Tessa M. A. Peters Udo Engelke Danijela Petković Ramadža Tamara Žigman Ksenija Fumić Maša Davidović Sanda Huljev Frković Tibor Körmendy Diego Martinelli Antonio Novelli Francesca Romana Lepri Ron A. Wevers Ivo Barić |
| author_facet | Katarina Šikić Tessa M. A. Peters Udo Engelke Danijela Petković Ramadža Tamara Žigman Ksenija Fumić Maša Davidović Sanda Huljev Frković Tibor Körmendy Diego Martinelli Antonio Novelli Francesca Romana Lepri Ron A. Wevers Ivo Barić |
| author_sort | Katarina Šikić |
| collection | DOAJ |
| description | Abstract Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by SLC33A1 mutations, a gene coding for the acetyl‐CoA transporter‐1 (AT‐1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinical improvement. Here, we describe the clinical characteristics of two novel patients, one of them diagnosed by gene analysis and his sib postmortally based on clinical characteristics. We demonstrate a therapeutic trial with acetylation therapy, consisting of N‐acetylcysteine and ketogenic diet, in one of them. We provide biochemical data on N‐acetylated amino acids in cerebrospinal fluid (CSF) and plasma before and after starting this treatment regimen. Our results indicate that ketogenic diet and N‐acetylcysteine do not seem to normalize the concentrations of N‐acetylated amino acids in CSF or plasma. The overall metabolic pattern shows a trend toward lowered levels of N‐acetylated amino acids in CSF and to a lesser extent in plasma. Although there are some assumptions, the function of AT‐1 is still not clear and further studies are needed to better understand mechanisms underlying this complex disorder. |
| format | Article |
| id | doaj-art-e187b6f8a49a4393abc192ac0ae2ecfa |
| institution | OA Journals |
| issn | 2192-8312 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj-art-e187b6f8a49a4393abc192ac0ae2ecfa2025-08-20T02:12:38ZengWileyJIMD Reports2192-83122024-11-0165636137010.1002/jmd2.12439Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteineKatarina Šikić0Tessa M. A. Peters1Udo Engelke2Danijela Petković Ramadža3Tamara Žigman4Ksenija Fumić5Maša Davidović6Sanda Huljev Frković7Tibor Körmendy8Diego Martinelli9Antonio Novelli10Francesca Romana Lepri11Ron A. Wevers12Ivo Barić13Department of Pediatrics University Hospital Center Zagreb Zagreb CroatiaDonders Institute for Brain, Cognition and Behavior Radboud University Medical Center Nijmegen The NetherlandsDonders Institute for Brain, Cognition and Behavior Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pediatrics University Hospital Center Zagreb Zagreb CroatiaDepartment of Pediatrics University Hospital Center Zagreb Zagreb CroatiaDepartment of Laboratory Diagnostics University Hospital Centre Zagreb Zagreb CroatiaDepartment of Pediatrics University Hospital Center Zagreb Zagreb CroatiaDepartment of Pediatrics University Hospital Center Zagreb Zagreb CroatiaDepartment of Diagnostic Neuroradiology University Hospital Centre Zagreb Zagreb CroatiaDivision of Metabolic Diseases, Department of Paediatric Subspecialties and Liver‐Kidney Transplantation Bambino Gesù Children's Hospital Rome ItalyTranslational Cytogenomics Research Unit Bambino Gesù Children's Hospital, IRCCS Rome ItalyTranslational Cytogenomics Research Unit Bambino Gesù Children's Hospital, IRCCS Rome ItalyDonders Institute for Brain, Cognition and Behavior Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pediatrics University Hospital Center Zagreb Zagreb CroatiaAbstract Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by SLC33A1 mutations, a gene coding for the acetyl‐CoA transporter‐1 (AT‐1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinical improvement. Here, we describe the clinical characteristics of two novel patients, one of them diagnosed by gene analysis and his sib postmortally based on clinical characteristics. We demonstrate a therapeutic trial with acetylation therapy, consisting of N‐acetylcysteine and ketogenic diet, in one of them. We provide biochemical data on N‐acetylated amino acids in cerebrospinal fluid (CSF) and plasma before and after starting this treatment regimen. Our results indicate that ketogenic diet and N‐acetylcysteine do not seem to normalize the concentrations of N‐acetylated amino acids in CSF or plasma. The overall metabolic pattern shows a trend toward lowered levels of N‐acetylated amino acids in CSF and to a lesser extent in plasma. Although there are some assumptions, the function of AT‐1 is still not clear and further studies are needed to better understand mechanisms underlying this complex disorder.https://doi.org/10.1002/jmd2.12439acetylated amino acidsacetyl‐CoA transporterHuppke–Brendel syndromeketogenic dietN‐acetylcysteineprotein acetylation |
| spellingShingle | Katarina Šikić Tessa M. A. Peters Udo Engelke Danijela Petković Ramadža Tamara Žigman Ksenija Fumić Maša Davidović Sanda Huljev Frković Tibor Körmendy Diego Martinelli Antonio Novelli Francesca Romana Lepri Ron A. Wevers Ivo Barić Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine JIMD Reports acetylated amino acids acetyl‐CoA transporter Huppke–Brendel syndrome ketogenic diet N‐acetylcysteine protein acetylation |
| title | Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine |
| title_full | Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine |
| title_fullStr | Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine |
| title_full_unstemmed | Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine |
| title_short | Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine |
| title_sort | huppke brendel syndrome novel cases and a therapeutic trial with ketogenic diet and n acetylcysteine |
| topic | acetylated amino acids acetyl‐CoA transporter Huppke–Brendel syndrome ketogenic diet N‐acetylcysteine protein acetylation |
| url | https://doi.org/10.1002/jmd2.12439 |
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