Proton MR Spectroscopy of the brain in children with neuronopathic Gaucher’s disease

Razek, Ahmed Abdel Khalek Abdel; Abdalla, Ahmed; Gaber, Nahed Abdel; Fathy, Abeer; Megahed, Ahmed; Barakat, Tarek; Alsayed, Mona Abdel Latif

doi:10.1007/s00330-013-2924-9

Cited by 26 publications

(11 citation statements)

References 36 publications

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“…The Korean version of modified Barthel index (K-MBI) was measured every 2–2.5 years. Brain magnetic resonance spectroscopy (MRS) was performed every year to evaluate the changes in the metabolite values of N -acetyl-aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) in the frontal white matter and occipital cortex that are known to be affected in nGD 16 17. We also examined the metabolite of the basal ganglia and cerebellum (dentate nucleus), the areas that control exercise and equilibrium functions and where storage cell accumulation has been identified as well 18.…”

Section: Methodsmentioning

confidence: 99%

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy

et al. 2019

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BackgroundAmbroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.MethodsABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.ResultsEnhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2–8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.ConclusionsLong-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

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Section: Methodsmentioning

confidence: 99%

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy

et al. 2019

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“…For instance, functional MRI (fMRI) can detect brain abnormalities that conventional MRI cannot spot in temporal lobe epilepsy and autism [ 31 , 32 ]. Similarly, proton magnetic resonance spectroscopy (H-MRS) can detect abnormalities in cases diagnosed with neuronopathic Gaucher’s disease (NGD) [ 33 ]. Thanks to the advanced technology, the fMRI and H-MRS can also predict the severity of the disease even at an early age of which might be correlated with genotypes.…”

Section: Introductionmentioning

confidence: 99%

Calcium channelopathies and intellectual disability: a systematic review

Kessi

Chen

Peng

et al. 2021

Orphanet J Rare Dis

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Background Calcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium channelopathies (CCs) and intellectual disability (ID)/global developmental delay (GDD) has been poorly investigated. We hypothesised that CCs play a major role in the development of ID/GDD and that both gain- and loss-of-function variants of calcium channel genes can induce ID/GDD. As a result, we performed a systematic review to investigate the contribution of CCs, potential mechanisms underlying their involvement in ID/GDD, advancements in cell and animal models, treatments, brain anomalies in patients with CCs, and the existing gaps in the knowledge. We performed a systematic search in PubMed, Embase, ClinVar, OMIM, ClinGen, Gene Reviews, DECIPHER and LOVD databases to search for articles/records published before March 2021. The following search strategies were employed: ID and calcium channel, mental retardation and calcium channel, GDD and calcium channel, developmental delay and calcium channel. Main body A total of 59 reports describing 159 cases were found in PubMed, Embase, ClinVar, and LOVD databases. Variations in ten calcium channel genes including CACNA1A, CACNA1C, CACNA1I, CACNA1H, CACNA1D, CACNA2D1, CACNA2D2, CACNA1E, CACNA1F, and CACNA1G were found to be associated with ID/GDD. Most variants exhibited gain-of-function effect. Severe to profound ID/GDD was observed more for the cases with gain-of-function variants as compared to those with loss-of-function. CACNA1E, CACNA1G, CACNA1F, CACNA2D2 and CACNA1A associated with more severe phenotype. Furthermore, 157 copy number variations (CNVs) spanning calcium genes were identified in DECIPHER database. The leading genes included CACNA1C, CACNA1A, and CACNA1E. Overall, the underlying mechanisms included gain- and/ or loss-of-function, alteration in kinetics (activation, inactivation) and dominant-negative effects of truncated forms of alpha1 subunits. Forty of the identified cases featured cerebellar atrophy. We identified only a few cell and animal studies that focused on the mechanisms of ID/GDD in relation to CCs. There is a scarcity of studies on treatment options for ID/GDD both in vivo and in vitro. Conclusion Our results suggest that CCs play a major role in ID/GDD. While both gain- and loss-of-function variants are associated with ID/GDD, the mechanisms underlying their involvement need further scrutiny.

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“…Enzyme replacement therapy (ERT) is the standard of care for patients with types 1 and 3 GD and frequently ameliorates the extent of visceral, hematologic and bony manifestations [10] , [11] , [12] . It consists of long-term biweekly infusions of a recombinant analogue of the missing human enzyme glubocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide [7] .…”

Section: Discussionmentioning

confidence: 99%

Symmetric, bilateral upper and lower extremity lucent lesions in a patient with Gaucher's disease on enzyme replacement therapy

Kuhn

Makusha

Bokhari

2020

Radiology Case Reports

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We report a case of a 6-year old girl with known type 3 Gaucher's Disease on enzyme replacement therapy who developed bilateral, symmetric osteolytic lesions in her humeri and femurs. While this manifestation of Gaucher's disease has been previously documented, it is an exceedingly rare variation. We observe that this patient shares 2 commonalities with 3 other patients reported in the literature to present with this phenotype. First, the patient's L444P/L444P genotype, present in approximately 11% of all Gaucher's patients, was also seen in these other patients. Second, like the other patients, this patient was treated with enzyme replacement therapy. It is unknown whether there is a correlation between these 2 independent variables and this rare phenotype, and further investigation may be warranted.

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Proton MR Spectroscopy of the brain in children with neuronopathic Gaucher’s disease

Cited by 26 publications

References 36 publications

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy

Calcium channelopathies and intellectual disability: a systematic review

Symmetric, bilateral upper and lower extremity lucent lesions in a patient with Gaucher's disease on enzyme replacement therapy

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