Similarities and differences between Gaucher disease and acid sphingomyelinase deficiency: An algorithm to support the diagnosis

Cappellini, Maria Domenica; Motta, Irene; Barbato, Antonio; Giuffrida, Gaetano; Manna, Raffaele; Carubbi, Francesca; Giona, Fiorina

doi:10.1016/j.ejim.2022.11.028

Cited by 3 publications

(3 citation statements)

References 23 publications

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“…A few of signs and symptoms of Gaucher disease are also found in Acid Sphingomyelinase Deficiency (ASMD) or Niemann Pick A/B disease [ 10 ]. It is caused by mutations in the SMPD1 gene coding for acid sphingomyelinase (ASM), which is necessary for sphingomyelin metabolism into ceramide and phosphocholine.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Niemann Pick A/B is rarer than GD, with an estimated incidence between 1:100,000 and 1:264,000 in the general population [ 14 ]. Therefore, the presence of several clinical manifestations peculiar to both disorders should alert clinicians to think not only of Gaucher disease but also ASMD [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, molecular markers, such as, glucosphingosine (Lyso-Gb1) and chitotriosidase in Gaucher disease, and lysosphingomyelin (Lyso-SM) and lysosphingomyelin 509 (Lyso-SM-509), have also been found to be elevated in ASMD [ 17 ]. Several algorithms for pediatric metabolists and physicians involved in diagnosis and treatment of LSD have provided simple, convenient, and sensitive tools for diagnosing late-onset forms of GD and ASMDthat show the possible overlap in clinical presentation [ 10 , 16 , 18 ]. In this study, we present for the first time the results of the enzymatic activity of both glucocerebrosidase and acid sphingomyelinase in 627 patients with an initial clinical suspicion of Gaucher disease from hematology, internal medicine, and pediatric centers throughout Italy.…”

Section: Introductionmentioning

confidence: 99%

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Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis

Giacomarra,

Colomba,

Francofonte

et al. 2024

JCM

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Background: Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis. For this reason, in patients with an initial clinical suspicion of Gaucher disease, we aimed to carry out a parallel screening of acid sphingomyelinase and glucocerebrosidase. Methods: Peripheral blood samples of 627 patients were collected, and enzymatic activity analysis was performed on both glucocerebrosidase and acid sphingomyelinase. The specific gene was studied in samples with null or reduced enzymatic activity. Specific molecular biomarkers helped to achieve the correct diagnosis. Results: In 98.7% of patients, normal values of glucocerebrosidase activity excluded Gaucher disease. In 8 of 627 patients (1.3%), the glucocerebrosidase enzymatic activity assay was below the normal range, so genetic GBA1 analysis confirmed the enzymatic defect. Three patients (0.5%) had normal glucocerebrosidase activity, so they were not affected by Gaucher disease, and showed decreased acid sphingomyelinase activity. SMPD1 gene mutations responsible for Acid Sphingomyelinase Deficiency were found. The levels of specific biomarkers found in these patients further strengthened the genetic data. Conclusions: Our results suggest that in the presence of typical signs and symptoms of Gaucher disease, Acid Sphingomyelinase Deficiency should be considered. For this reason, the presence of hepatosplenomegaly, thrombocytopenia, leukocytopenia, and anemia should alert clinicians to analyze both enzymes by a combined screening. Today, enzyme replacement therapy is available for the treatment of both pathologies; therefore, prompt diagnosis is essential for patients to start accurate treatment and to avoid diagnostic delay.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis

Giacomarra,

Colomba,

Francofonte

et al. 2024

JCM

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Unexplained splenomegaly as a diagnostic marker for a rare but severe disease with an innovative and highly effective new treatment option: A case report

Van Baelen,

Verhulst,

Eyskens

2024

Molecular Genetics and Metabolism Reports

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Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review

Barbato,

Vergatti,

Giaquinto

et al. 2024

JBMR Plus

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Introduction The skeletal anomalies represent a characteristic feature of Gaucher disease type 1 (GD1). We evaluated the impact of an integrated therapy with Enzyme Replacement Therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. Methods From January 1st,2015 to February 28th, 2019, all GD1 patients referring to Federico II University were enrolled and treated with the integrated therapy. The bone turnover markers (BTMs) and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). Results We enrolled 25 GD1 patients, all showing 25OHD levels <50 nmol/l (hypovitaminosis D) at T0. The response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis and 7 BMD Z-score ≤ -2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared to those without bone anomalies. During the 2-years follow-up no new bone anomalies occurred. At T24, the BMD remained stable in the entire study cohort and in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Conclusion In GD1 patients, hypovitaminosis D is prevalent. The response to cholecalciferol treatment is effective but different to healthy subjects and to patients with metabolic bone disorders. The integrated therapy including ERT, cholecalciferol, and bone diet guarantee the bone health.

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Similarities and differences between Gaucher disease and acid sphingomyelinase deficiency: An algorithm to support the diagnosis

Cited by 3 publications

References 23 publications

Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis

Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis

Unexplained splenomegaly as a diagnostic marker for a rare but severe disease with an innovative and highly effective new treatment option: A case report

Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review

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