| Autor: |
Gayed MM; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., Jung SH; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., Huggins E; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., Rodriguez-Rassi E; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., DeArmey S; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., Kishnani PS; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA., Stiles AR; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.; Biochemical Genetics Laboratory, Duke University Health System, Durham, NC 27713, USA. |
| Abstrakt: |
Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb 1 ), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb 1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb 1 . We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb 1 . Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb 1 ; and another with normal CHITO and platelets, but increasing lyso-Gb 1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb 1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients. |
