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. 2023 Jun 16;18(1):151.
doi: 10.1186/s13023-023-02760-z.

GAU-PED study for early diagnosis of Gaucher disease in children with splenomegaly and cytopenia

Andrea Pession  1 , Maja Di Rocco  2 , Francesco Venturelli  3 , Barbara Tappino  2 , William Morello  4 , Nicola Santoro  5 , Paola Giordano  6 , Beatrice Filippini  7 , Simona Rinieri  8 , Giovanna Russo  9 , Katia Girardi  10 , Antonio Ruggiero  11 , Eulalia Galea  12 , Roberto Antonucci  13 , Nicola Tovaglieri  14 , Fulvio Porta  15 , Immacolata Tartaglione  16 , Fiorina Giona  17 , Franca Fagioli  18 , Alberto Burlina  19 ; Pediatric Gaucher Study Group
Collaborators, Affiliations

GAU-PED study for early diagnosis of Gaucher disease in children with splenomegaly and cytopenia

Andrea Pession et al. Orphanet J Rare Dis. .

Abstract

Background: Gaucher disease (GD) diagnosis can be delayed due to non-specific symptoms and lack of awareness, leading to unnecessary procedures and irreversible complications. GAU-PED study aims to assess GD prevalence in a high-risk pediatric population and the presence, if any, of novel clinical or biochemical markers associated with GD.

Materials and methods: DBS samples were collected and tested for β-glucocerebrosidase enzyme activity for 154 patients selected through the algorithm proposed by Di Rocco et al. Patients showing β-glucocerebrosidase activity below normal values were recalled to confirm the enzyme deficiency with the gold standard essay on cellular homogenate. Patients tested positive at the gold standard analysis were evaluated through GBA1 gene sequencing.

Results: 14 out of 154 patients were diagnosed with GD, with a prevalence of 9.09% (5.06-14.78%, CI 95%). Hepatomegaly, thrombocytopenia, anemia, growth delay/deceleration, elevated serum ferritin, elevated Lyso-Gb1 and chitotriosidase were significantly associated with GD.

Conclusions: GD prevalence in a pediatric population at high-risk appeared to be higher compared to high-risk adults. Lyso-Gb1 was associated with GD diagnosis. The algorithm proposed by Di Rocco et al. can potentially improve the diagnostic accuracy of pediatric GD, allowing the prompt start of therapy, aiming to reduce irreversible complications.

Keywords: Cytopenia; Gaucher disease; Lysosomal storage disease; Splenomegaly; Thrombocytopenia.

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Conflict of interest statement

AP received honoraria from BioMarin Pharmaceutical Inc, Dicopharm, PTC Therapeutics, and Sanofi for participation at advisory boards and speaking at their sponsored meetings. MDR received travel support and honoraria from Sanofi and Takeda. WM received travel grants and honoraria from Sanofi-Genzyme for speaking at sponsored meetings. NS receives honoraria from NOVARTIS and AMGEN for participation at advisory boards and speaking at their sponsored meetings. PG received honoraria from Bayer Roche Sobi for participation at advisory board. GR receives honoraria from NOVARTIS, AMGEN, GRIFOLS and BIOVALLEY for participation at advisory boards and speaking at their sponsored meetings. FG receives honoraria from Sanofi and Takeda for participation at advisory boards and speaking at their sponsored meetings. FF receives honoraria from Jazz Pharmaceutical, Dicopharm, Bayer, Takeda and Sanofi for participation at advisory boards and speaking at their sponsored. AB receives honoraria for advisory boards and speaking at their sponsored meetings from Takeda, BioMarin Pharmaceutical Inc, PTC Therapeutics, Sanofi-Genzyme. FP received honoraria by BIOTEST, TILLOMED, JAZZ, TAKEDA, CHIESI for participations to advisory boards and sponsored meetings. FV, BT, SR, KG, AR, EG, RA, NT, BF, IT, RM, BR, AT, GM, DR, MC, SS, DO, SL, AC have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Diagnostic algorithm for childhood splenomegaly and Cytopenia [16]
Fig. 2
Fig. 2
GAU-PED study flowchart. DBS: Dried blood spot
Fig. 3
Fig. 3
β-glucocerebrosidase enzyme activity comparison between patients with and without GD. a β-glucocerebrosidase activity on DBS; b β-glucocerebrosidase activity on cellular homogenate (Z-score)
Fig. 4
Fig. 4
a Lyso-GB1 values comparison between patients with or without GD. b Chitotriosidase values comparison between patients with or without GD
See this image and copyright information in PMC

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