The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here?

Weinreb, Neal J.; Göker-Alpan, Özlem; Kishnani, Priya S.; Longo, Nicola; Burrow, T.; Bernat, John A.; Gupta, Punita; Henderson, Nadene; Pedro, Hélio; Prada, Carlos E.; Vats, Divya; Pathak, Rashmi; Wright, Ekaterina; Fıçıcıoğlu, Can

doi:10.1016/j.ymgme.2022.03.001

Cited by 29 publications

(56 citation statements)

References 178 publications

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Section: Discussionmentioning

confidence: 99%

“…The phenotypic heterogeneity of GD presents many challenges in patient diagnosis and management [ 32 ]. While the clinical benefits of treatment with ERT and/or SRT have been well documented in mouse models [ 33 ] and treatment naïve patients [ 13 , 34 , 35 , 36 , 37 ], considerable variation in the clinical response to treatment exists [ 32 ]. In one study, a comparison of lyso-Gb 1 levels in patients on long-term ERT showed considerable inter- and intra-individual variability with higher concentrations of lyso-Gb 1 observed in patients treated with imiglucerase in comparison to velaglucerase alfa [ 14 ] and with a steeper and faster decrease of lyso-Gb 1 levels in those treated with velaglucerase alfa [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a change in treatment should warrant a physical examination, complete blood count (hemoglobin and platelets), and lyso-Gb 1 analysis. For pediatric patients with type 3 GD, additional neurological and ophthalmological investigations are recommended [ 32 ]. The initial assessment and monitoring guidelines for adults with type 1 GD are in line with the aforementioned pediatric recommendations aside from biomarker monitoring which have not been update to include lyso-Gb 1 analysis; measurement of non-specific analytes CHITO, angiotensin converting enzyme, and tartrate resistant acid phosphatase are still recommended [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Gayed

Jung

Huggins

et al. 2022

IJMS

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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-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 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-Gb1. 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-Gb1. 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-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Gayed

Jung

Huggins

et al. 2022

IJMS

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“…Symptoms for GD allow us to screen and confirm the disease by the measurement of GCase activity and by variant identification in GBA1 . Additionally, biomarkers, such as chitriosidase activity, CCL18/PARC concentration, or glucosylsphingosine concentration, are available for diagnosis and for monitoring the response to therapy [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson’s Disease

Frutos

Almeida

Murillo-Saich

et al. 2022

IJMS

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Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography–mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

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“…Early identi cation is crucial to improving the ultimate outcomes because early treatment can prevent the development of irreversible complications. (2,10) Bone involvement is variable and macrophages lled with lipid material known as Gaucher's cells are a cardinal feature of the disease. Diagnosis can also be con rmed by mutation analysis.…”

Section: Introductionmentioning

confidence: 99%

Gaucher Disease in 20-Month-Old Ethiopian Boy with a Massive Splenomegaly and Failure to Grow: Challenges in Case Management

Hassen

abubeker

Tufa

et al. 2022

Preprint

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Background: Gaucher disease is an autosomal recessive lipid storage disorder caused by genetic mutations in the GBA gene. Symptoms are variable, range from asymptomatic to perinatal lethality, and can occur at any age. Case report: This report details a case of a 20-month-old male born in Harar and referred to Hiwot Fana Specialized University Hospital, Harar, Ethiopia for evaluation of severe acute malnutrition, hepatosplenomegaly, and Developmental regression since the age of 8 months. He was well known for receiving blood transfusions due to anemia with persistent thrombocytopenia multiple times. On clinical examination, there was no dimorphism but had pallor, multiple lymphadenopathies with enlarged Liver, and a massive spleen. His assessment showed anemia was associated with marked thrombocytopenia. Bone marrow biopsy revealed Gaucher cells, confirmatory test for Gaucher disease, B-glucocerebrosidase activity results showed low activity and mutation detected in homozygous condition c. 1448 T>C p. (Leu483Pro). Over a year his abdomen became progressively distended, and he began to have breathing problems. Unfortunately, while seeking donated medical treatment, he died suddenly in the hospital after serious bleeding mainly due to a delayed diagnosis and a lack of supplies of medicines. This case was presented to demonstrate the challenges in diagnosing and treating Gaucher disease, especially in a resource-constrained environment like ours Conclusions: This case demonstrates the need to include this disease in the differential diagnosis when dealing with unexplained thrombocytopenia, anemia, hepatomegaly, and splenomegaly

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The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here?

Cited by 29 publications

References 178 publications

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson’s Disease

Gaucher Disease in 20-Month-Old Ethiopian Boy with a Massive Splenomegaly and Failure to Grow: Challenges in Case Management

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