Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions
Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency disorders caused by <i>ASAH1</i> gene mutations. Currently, 73 different mutations in the <i>ASAH1</i> gene h...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/2/274 |
| _version_ | 1827758286012678144 |
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| author | Annie Kleynerman Jitka Rybova Mary L. Faber William M. McKillop Thierry Levade Jeffrey A. Medin |
| author_facet | Annie Kleynerman Jitka Rybova Mary L. Faber William M. McKillop Thierry Levade Jeffrey A. Medin |
| author_sort | Annie Kleynerman |
| collection | DOAJ |
| description | Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency disorders caused by <i>ASAH1</i> gene mutations. Currently, 73 different mutations in the <i>ASAH1</i> gene have been described in humans. These mutations lead to reduced ACDase activity and ceramide (Cer) accumulation in many tissues. Presenting as divergent clinical phenotypes, the symptoms of FD vary depending on central nervous system (CNS) involvement and severity. Classic signs of FD include, but are not limited to, a hoarse voice, distended joints, and lipogranulomas found subcutaneously and in other tissues. Patients with SMA-PME lack the most prominent clinical signs seen in FD. Instead, they demonstrate muscle weakness, tremors, and myoclonic epilepsy. Several ACDase-deficient mouse models have been developed to help elucidate the complex consequences of Cer accumulation. In this review, we compare clinical reports on FD patients and experimental descriptions of ACDase-deficient mouse models. We also discuss clinical presentations, potential therapeutic strategies, and future directions for the study of FD and SMA-PME. |
| first_indexed | 2024-03-11T09:05:35Z |
| format | Article |
| id | doaj.art-036a553ab30a4c73ac17ddd27203134e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:05:35Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-036a553ab30a4c73ac17ddd27203134e2023-11-16T19:22:50ZengMDPI AGBiomolecules2218-273X2023-02-0113227410.3390/biom13020274Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic InterventionsAnnie Kleynerman0Jitka Rybova1Mary L. Faber2William M. McKillop3Thierry Levade4Jeffrey A. Medin5Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USALaboratoire de Biochimie Métabolique, CHU Toulouse, and INSERM U1037, Centre de Recherches en Cancérologie de Toulouse, Université Paul Sabatier, 31062 Toulouse, FranceDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USAFarber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency disorders caused by <i>ASAH1</i> gene mutations. Currently, 73 different mutations in the <i>ASAH1</i> gene have been described in humans. These mutations lead to reduced ACDase activity and ceramide (Cer) accumulation in many tissues. Presenting as divergent clinical phenotypes, the symptoms of FD vary depending on central nervous system (CNS) involvement and severity. Classic signs of FD include, but are not limited to, a hoarse voice, distended joints, and lipogranulomas found subcutaneously and in other tissues. Patients with SMA-PME lack the most prominent clinical signs seen in FD. Instead, they demonstrate muscle weakness, tremors, and myoclonic epilepsy. Several ACDase-deficient mouse models have been developed to help elucidate the complex consequences of Cer accumulation. In this review, we compare clinical reports on FD patients and experimental descriptions of ACDase-deficient mouse models. We also discuss clinical presentations, potential therapeutic strategies, and future directions for the study of FD and SMA-PME.https://www.mdpi.com/2218-273X/13/2/274ceramidelysosomal storage disorderSMA-PMEFarber diseaselipogranulomatosisacid ceramidase |
| spellingShingle | Annie Kleynerman Jitka Rybova Mary L. Faber William M. McKillop Thierry Levade Jeffrey A. Medin Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions Biomolecules ceramide lysosomal storage disorder SMA-PME Farber disease lipogranulomatosis acid ceramidase |
| title | Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions |
| title_full | Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions |
| title_fullStr | Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions |
| title_full_unstemmed | Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions |
| title_short | Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions |
| title_sort | acid ceramidase deficiency bridging gaps between clinical presentation mouse models and future therapeutic interventions |
| topic | ceramide lysosomal storage disorder SMA-PME Farber disease lipogranulomatosis acid ceramidase |
| url | https://www.mdpi.com/2218-273X/13/2/274 |
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