Livia Paskulin

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease

Abstract The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study. Nine of these participants were males, and seventeen had type I GD. All patients were given either enzyme replacement (n = 16) or substrate reduction therapy (n = 2), and ferritin was found to decrease from 756 [318-1441] ng/mL at baseline to 521 [227-626] ng/mL (p=0.025) after 28.8 month soft treatment. Serum ferritin levels did not correlate with measures of disease severity, but showed an association with age at onset of treatment (ρ= 0.880; n = 18; p < 0.001). In conclusion, although serum ferritin did not correlate with disease severity, after a median 28.8 months of treatment, clinical outcomes had clearly improved, and ferritin levels had decreased.

PP044 Adherence To Enzyme Replacement Therapy In Gaucher Disease

No publications reporting on flare/pseudoseptic reactions with Synolis V-A were found. There are limited case series of patients treated with Synolis V-A, with most evidence coming from a prospective post-marketing surveillance case series, which showed reduced pain and functional impairment at 6 months. Adverse reactions were rare. CGH’s own small trial of Synolis V-A did not show any flare reactions.

Serum β2-microglobulin is frequently elevated in type 1 Gaucher patients

β2-Microglobulin is the major prognostic factor in multiple myeloma, a known comorbidity of Gaucher disease. We evaluated herein serum β2-microglobulin levels of 31 type 1 Gaucher patients; for 8/31 patients, pre- and post-treatment comparisons were made. Thirteen patients (on treatment = 6) had high levels of β2-microglobulin, and showed higher chitotriosidase activity and Severity Score Index, and lower concentration of platelets, than patients with normal levels. Levels of β2-microglobulin correlated with chitotriosidase activity (ρ = 0.65; p < 0.01), platelets (ρ = − 0.42; p = 0.02) and α1- (ρ = 0.43; p = 0.02) and α2-protein bands (ρ = − 0.40; p = 0.03). Regarding pre- and post-treatment values, median β2-microglobulin levels decreased after treatment (pre- = 2931 ng/mL; post- = 1970 ng/mL; p < 0.01). Our data suggest that levels of serum β2-microglobulin are frequently elevated in type 1 Gaucher patients, correlate with severity of the disease and decrease after treatment.

Gastrointestinal disorders and miglustat therapy: A case report

CO RR EC TE D P RO OF the juvenile forms by age of onset, rate of disease progression and age of death. There are no approved treatments for gangliosidoses. Biomarkers for evaluating disease phenotype, disease progression, and response to therapies would serve to facilitate the design and development of potential treatment of these diseases, but such biomarkers have not been identified. Increasing evidence from animal models and human cadavers suggests inflammatory mediators in the CNS play a role in disease pathology and progression. Hypothesis: The more rapid disease progression and more severe clinical phenotype of the infantile GM1and GM2-gangliosidosis relative to juvenile forms will coincide with levels of disease specific inflammatory mediators in the CNS. Methods: CSF and serum inflammatory markers were quantified by immunoassay in 8 children with infantile forms of gangliosidoses (including patients with Tay–Sachs disease, Sandhoff disease and GM1 gangliosidosis). Findings were compared to values from 4 patients with more slowly progressing forms of gangliosidoses (i.e., late-infantile, juvenile forms) and to values of 9 children with mucopolysaccharidosis (MPS) diseases. Results: Of 188 analytes assayed, elevated inflammatory markers occurredmore often in the CSF of infantile gangliosidosis patients when compared to the more slowly progressing forms of juvenile gangliosidosis and MPS disease. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1β, TNFR2. Additional candidates for CNS and serum inflammatory markers for infantile and juvenile phenotypes were found. Conclusion: This study identified candidate biomarkers of CNS inflammatory disease in infantile and juvenile gangliosidoses that are promising as markers for evaluating CNS disease progression, distinguishing infantile and juvenile phenotypes and monitoring response to future therapeutic interventions in the gangliosidoses. (Supported by Lysosomal Disease Network, NIH U54NS065768 and Pharmacotherapy for InheritedMetabolic Diseases Fellowship training program, GenzymeSanofi.)