| Autor: |
Kleynerman A; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Rybova J; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Faber ML; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., McKillop WM; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Levade T; Laboratoire de Biochimie Métabolique, CHU Toulouse, and INSERM U1037, Centre de Recherches en Cancérologie de Toulouse, Université Paul Sabatier, 31062 Toulouse, France., Medin JA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. |
| Abstrakt: |
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 ASAH1 gene mutations. Currently, 73 different mutations in the ASAH1 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. |
