Use of IDEAL-IQ in Quantifying Femoral Bone Marrow Involvement in Gaucher Disease.

OBJECTIVE: To quantitatively measure femoral bone marrow involvement in patients with Gaucher disease (GD) by using fat fraction (FF) derived from the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) technique. METHODS: Bilateral femora of 23 patients with type 1 GD receiving low-dose imiglucerase treatment were prospectively scanned using structural magnetic resonance imaging sequences and an IDEAL-IQ sequence. Femoral bone marrow involvement was evaluated by both semiquantification (bone marrow burden [BMB] score based on magnetic resonance imaging structural images) and quantification (FF derived from IDEAL-IQ) methods. These patients were further divided into subgroups according to whether they underwent splenectomy or had bone complications. The interreader agreement of measurements and the correlation between FF and clinical status were statistically analyzed. RESULTS: In patients with GD, both BMB and FF evaluation of femora showed good interreader concordance (intraclass correlation coefficient = 0.98 and 0.99, respectively), and FF highly correlated with BMB score ( P < 0.001). The longer the duration of disease, the lower the FF ( P = 0.026). Femoral FF was lower in subgroups with splenectomy or bone complications than those without splenectomy or bone complications (0.47 ± 0.08 vs 0.60 ± 0.15, 0.51 ± 0.10 vs 0.61 ± 0.17, respectively, both P < 0.05). CONCLUSION: Femoral FF derived from IDEAL-IQ could be used to quantify femoral bone marrow involvement in patients with GD, and low bone marrow FF may predict worse outcomes of GD patients in this small-scale study.

Gaucher: A Systematic Review on Oral and Radiological Aspects.

Background and Objectives: Gaucher disease (GD) is a lysosomal storage disorder with the genetic autosomal recessive transmission. Bone involvement is a prevalent finding in Gaucher disease. It causes deformity and limits daily activities and the quality of life. In 75% of patients, there is bone involvement. This review aims to evaluate the principal findings in the jaw by a Cone-beam computed tomography (CBTC) and X-ray orthopantomography; Materials and Methods: PubMed, Web of Science, Lilacs and Scopus were systematically searched until 31 December 2022. In addition, a manual search was performed using the bibliography of selected articles and a Google Scholar search. Clinical studies were selected that considered principal radiographic findings in radiography in a group of patients affected by GD. Results: Out of 5079 papers, four studies were included. The main findings are generalized rarefaction and enlarged narrow space, anodontia. Conclusions: The exact mechanism of bone manifestation is probably due to the infiltration of Gaucher cells in the bone marrow and, consequently, the destruction of bone architecture. All long bones are a potential means of skeletal manifestation. The jaw is more affected than the maxilla, and the principal features are cortical thinning, osteosclerosis, pseudocystic lesions, mental demineralization, flattening in the head of the condyle, effacement of anatomical structures, thickening of maxillary sinus mucosa. The dentist plays a crucial role in diagnosing and treating these patients. Sometimes the diagnosis can be made by a simple panoramic radiograph. All long bones are affected, and the mandible is particularly involved.

Fat fraction quantification of bone marrow in the lumbar spine using the LiverLab assessment tool in healthy adult volunteers and patients with Gaucher disease.

BACKGROUND: Magnetic Resonance Imaging is used for evaluation of bone in Gaucher disease (GD), but a widely available quantitative scoring method remains elusive. AIMS: The study purpose was to assess the reproducibility of the LiverLab tool for assessing bone marrow fat fraction (FF) and determine whether it could differentiate GD patients from healthy subjects. METHODS: Ten healthy volunteers and 18 GD patients were prospectively recruited. FF was calculated at L3, L4 and L5. GD patient bone marrow burden (BMB) score assessed by one observer. Inter and intra-rater agreement assessed with Bland-Altman data plots. Differences in FF between healthy volunteers versus GD patients and between subjects treated versus not treated assessed using two-sample t-tests. In GD patients, the relationship between FF, BMB and glucosylsphingosine was determined using the Pearson's correlation coefficient. RESULTS: Healthy volunteer mean FF was 0.36, standard deviation (SD) 0.10 (range 0.20-0.57). Intra and inter-rater SD were both 0.02. GD patient mean FF was 0.40, SD 0.13 (range 0.09-0.57). No statistical difference was shown between healthy volunteers and GD patients (P = 0.447) or between GD patients whether on enzyme replacement therapy or not (P = 0.090). No significant correlation between mean FF and total BMB (r = -0.525, P = 0.253) or between FF and glucosylsphingosine levels (r = 0.287, P = 0.248). CONCLUSION: Excellent reproducibility of LiverLab FF measurements across studies and observers is comparable to Dixon quantitative chemical shift imaging (QCSI). Lack of statistical difference between GD patients and controls may be explained by limited patient numbers, active treatment or mild disease severity in untreated patients.

Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease.

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA. Purpose To assess the utility of DXA and radiographic femoral cortical thickness measurements as predictors of fragility fracture in patients with GD with long-term follow-up (up to 30 years). Materials and Methods Patients with GD age 16 years and older with a detailed medical history, at least one bone image (DXA and/or radiographs), and minimum 2 years follow-up were retrospectively identified using three merged UK-based registries (Gaucherite study, enrollment 2015-2017; Clinical Bone Registry, enrollment 2003-2006; and Mortality Registry, enrollment 1993-2019). Cortical thickness index (CTI) and canal-to-calcar ratio (CCR) were measured by two independent observers, and inter- and intraobserver reliability was calculated. The fracture-predictive value of DXA, CTI, CCR, and cutoff values were calculated using receiver operating characteristic curves. Statistical differences were assessed using univariable and multivariable analysis. Results Bone imaging in 247 patients (123 men, 124 women; baseline median age, 39 years; IQR, 27-50 years) was reviewed. The median follow-up period was 11 years (IQR, 7-19 years; range, 2-30 years). Thirty-five patients had fractures before or at first bone imaging, 23 patients had fractures after first bone imaging, and 189 patients remained fracture-free. Inter- and intraobserver reproducibility for CTI/CCR measurements was substantial (range, 0.96-0.98). In the 212 patients with no baseline fracture, CTI (cutoff, ≤0.50) predicted future fractures with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.84, 0.99; sensitivity, 92%; specificity, 96%) than DXA T-score at total hip (AUC, 0.78; 95% CI: 0.51, 0.91; sensitivity, 64%; specificity, 93%), femoral neck (AUC, 0.73; 95% CI: 0.50, 0.86; sensitivity, 64%; specificity, 73%), lumbar spine (AUC, 0.69; 95% CI: 0.49, 0.82; sensitivity, 57%; specificity, 63%), and forearm (AUC, 0.78; 95% CI: 0.59, 0.89; sensitivity, 70%; specificity, 70%). Conclusion Radiographic cortical thickness index of 0.50 or less was a reliable independent predictor of fracture risk in Gaucher disease. Clinical trial registration no. NCT03240653 © RSNA, 2022 Supplemental material is available for this article.

Pre- and post-therapeutic evaluation of liver and spleen in type I and type III Gaucher's disease using diffusion tensor imaging.

PURPOSE: To assess the role of diffusion tensor imaging in assessing liver and splenic parenchymal infiltration in Gaucher's disease (G.D.) type I and III before and after therapy. METHODS: A prospective study was conducted upon 28 consecutive patients with G.D. type I and III and 28 age and sex-matched controls. They underwent an MRI and DTI of the liver and spleen. Mean diffusivity (M.D.) and fractional anisotropy (F.A.) values of the liver and spleen were evaluated before and after treatment and compared with control. RESULTS: There was a statistically significant difference in the M.D. value of the liver and spleen between untreated patients and controls and between control and treated patients and in the M.D. value of the liver and spleen between untreated and treated patients. There is a statistically significant difference in the F.A. value of the liver and spleen between untreated patients and controls and in the F.A. value of the liver and spleen between untreated and treated patients. Hemoglobin level was positively correlated with the M.D. value of the spleen. Clinical score was negatively correlated with M.D. value of the spleen and was positively correlated with F.A. values of the liver and F.A. values of the spleen. Spleen volume was negatively correlated with M.D. values of the spleen. CONCLUSION: Significant difference in M.D. and F.A. values of liver and splenic parenchyma in p atients with type I and III G.D. and controls, and between untreated and treated patients. The M.D. and F.A. values were well correlated with some biomarkers of disease activity.

A Rare Pitfall in Bone Mineral Densitometry: Gaucher Disease.

ABSTRACT: We report a rare case of type 3 Gaucher disease presenting with calcified mesenteric lymph nodes that interfere with bone mineral densitometric measurements.

Neuroimaging in Glucocerebrosidase-Associated Parkinsonism: A Systematic Review.

BACKGROUND: Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting carriers of GBA mutations/variants (GBA-NMC) constitute a potential PD preclinical population, whereas PD patients carrying some GBA mutations/variants (GBA-PD) have a higher risk of a more aggressive disease course. Different neuroimaging techniques are emerging as potential biomarkers in PD and have been used to study GBA-associated parkinsonism. OBJECTIVE: The aim is to critically review studies applying neuroimaging to GBA-associated parkinsonism. METHODS: Literature search was performed using PubMed and EMBASE databases (last search February 7, 2022). Studies reporting neuroimaging findings in GBA-PD, GD with and without parkinsonism, and GBA-NMC were included. RESULTS: Thirty-five studies were included. In longitudinal studies, GBA-PD patients show a more aggressive disease than iPD at both structural magnetic resonance imaging and 123-fluoropropylcarbomethoxyiodophenylnortropane single-photon emission computed tomography. Fluorodeoxyglucose-positron emission tomography and brain perfusion studies reported a greater cortical involvement in GBA-PD compared to iPD. Overall, contrasting evidence is available regarding GBA-NMC for imaging and clinical findings, although subtle differences have been reported compared with healthy controls with no mutations. CONCLUSIONS: Although results must be interpreted with caution due to limitations of the studies, in line with previous clinical observations, GBA-PD showed a more aggressive disease progression in neuroimaging longitudinal studies compared to iPD. Cognitive impairment, a "clinical signature" of GBA-PD, seems to find its neuroimaging correlate in the greater cortical burden displayed by these patients as compared to iPD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical and radiological evaluation of dentomaxillofacial involvement in Type I Gaucher disease.

OBJECTIVES: This study aimed to evaluate the oral findings and dentomaxillofacial involvement of patients diagnosed with Type I Gaucher Disease (GD), and to compare these findings with the control group. METHODS: A total of 32 patients, 5 males, and 11 females in both the study (range 19-60, mean age 34.56) and control group (range 18-49, mean age 34.63) were included in the study. The file records of all patients obtained in the first evaluation were examined, and the hematological, visceral, and bone examination findings were recorded. Subsequently, oral examinations were performed for oral findings and dentomaxillofacial involvement, and radiological examinations were performed in panoramic images and cone-beam computed tomography (CBCT) images. RESULTS: There was mandible involvement in 9 (56.3%), and involvement in both jaws in 4 (25.0%) of the patients with Type I GD. According to the CBCT findings, generalized rarefaction in 10 (62.5%) patients, enlarged marrow spaces in 12 (75.0%) patients, thinning of the lamina dura in 10 (62.5%) patients, and loss in the cortical borders of the mandibular canal in 7 (43.8%) patients were among the common radiographic findings. When the control and study group were compared, in panoramic images, a significant difference was found in terms of generalized rarefaction and enlarged marrow spaces, while significant differences were found in CBCT images regarding generalized rarefaction, enlarged marrow spaces, loss in the cortical margins of the mandibular canal and widening in the periodontal ligament space. CONCLUSIONS: The roadmap for the diagnosis of Gaucher lesions in the jawbones includes a comprehensive medical history and a clinical and radiological examination. In conclusion, dentists should be familiar with the dentomaxillofacial findings of GD and be aware of possible oral and dental complications that may develop.

New correlations between ocular parameters and disease severity in Spanish patients with Gaucher's disease Type I.

BACKGROUND: Gaucher's disease is associated with a high variety of structural and functional abnormalities in the eye, which do not always affect visual acuity. The purpose of this study was to analyse ocular features in Spanish patients with Gaucher's disease type I, and to investigate their possible correlation with phenotypic and burden parameters of this entity. METHODS: This cross-sectional observational study compared parameters belonging to 18 eyes from 9 Spanish patients with Gaucher's disease Type I with 80 eyes from 40 healthy controls. Complete ophthalmological examination included choroidal and retinal thickness maps with swept source optical coherence tomography. Systemic analysis included genotype, plasmatic biomarkers, [ferritin, chemokine ligand 18 (CCL18) and chitotriosidase (ChT)] and severity scoring systems results ["Gaucher Disease Severity Score Index Type I" (GauSSI-I) and "Gaucher disease severity scoring system" (GD-DS3)]. RESULTS: Nine subjects (18 eyes) were cases (female: 55.5%, mean age 45 years; male: 44.5%, mean age 36 years) and 40 subjects (80 eyes) were controls (female: 49%, mean age 50 years; male: 51%, mean age 55 years). There were no statistically significant differences when comparing ocular parameters (visual acuity; axial length, refractive errors, corneal parameters, lens, retinal and choroidal thickness) between case and control subjects (p>0.05). A statistically significant moderate correlation was observed between lower retinal thickness and choroidal quadrants thickness and greater disease severity scores. A lower central retinal thickness also correlates with higher biological plasmatic levels, and has a statistically significant association with the most affected patient with genotype N370S/Del 55pb. Conversely, higher pachymetry involves a more severe plasmatic concentration of biomarkers. CONCLUSIONS: Our results suggest that pachymetry, and retinal and choroidal thickness, are associated with burden biomarkers and disease severity index scores in Spanish patients with Gaucher's disease Type I.

Cardiopulmonary assessment of patients diagnosed with Gaucher's disease type I.

BACKGROUND: Understanding the basis of the phenotypic variation in Gaucher's disease (GD) has proven to be challenging for efficient treatment. The current study examined cardiopulmonary characteristics of patients with GD type 1. METHODS: Twenty Caucasian subjects (8/20 female) with diagnosed GD type I (GD-S) and 20 age- and sex-matched healthy controls (C), were assessed (mean age GD-S: 32.6 ± 13.1 vs. C: 36.2 ± 10.6, p > .05) before the initiation of treatment. Standard echocardiography at rest was used to assess left ventricular ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP). Cardiopulmonary exercise testing (CPET) was performed on a recumbent ergometer using a ramp protocol. RESULTS: LVEF was similar in both groups (GD-S: 65.1 ± 5.2% vs. C: 65.2 ± 5.2%, p > .05), as well as PAPS (24.1 ± 4.2 mmHg vs. C: 25.5 ± 1.3 mmHg, p > .05). GD-S had lower weight (p < .05) and worse CPET responses compared to C, including peak values of heart rate, oxygen consumption, carbondioxide production (VCO2 ), end-tidal pressure of CO2 , and O2 pulse, as well as HR reserve after 3 min of recovery and the minute ventilation/VCO2  slope. CONCLUSIONS: Patients with GD type I have an abnormal CPET response compared to healthy controls likely due to the complex pathophysiologic process in GD that impacts multiple systems integral to the physiologic response to exercise.

Bone marrow burden score is not useful as a follow-up parameter in stable patients with type 1 Gaucher disease after 5 years of treatment.

INTRODUCTION: Gaucher disease (GD) is one of the most prevalent lysosomal disorders, with an estimated incidence of 1 in 40,000 live births worldwide. Skeletal involvement is one of the main features of GD, causing morbidity and impacting long-term quality of life in patients with type 1 GD. OBJECTIVES: To characterize bone marrow infiltration in patients with type 1 GD followed at the Gaucher Disease Referral Center of Porto Alegre, Brazil, and to assess whether the Bone Marrow Burden score (BMB) correlates with clinical or laboratory parameters. We also evaluated whether the BMB score is a suitable parameter for long-term follow-up of patients with type 1 GD. METHODS: All included patients underwent magnetic resonance imaging for BMB score calculation at baseline, 1 year, and every other year thereafter or as clinically indicated from 2012 to 2018. RESULTS: The BMB score tended to decrease during the first 5 years of treatment, at a rate of -1.08 points per year; after the 5-year mark, BMB tended to remain stable. CONCLUSIONS: The BMB score is useful for response monitoring in the first five years of treatment. We recommend that, after 5 years of treatment, MRI for BMB evaluation should only be performed in non-adherent patients or in those who develop symptoms of acute skeletal disease.

Diffusion tensor imaging of vertebral bone marrow in children with Gaucher's disease type I and III: Pre- and post-therapy.

PURPOSE: To assess diffusion tensor imaging (DTI) of the vertebral bone marrow (BM) in children with Gaucher's disease (GD) types I and III before and after therapy. METHODS: Prospective study was conducted upon 25 children with GD type I (n = 17) and III (n = 8) and 13 age and sex-matched controls underwent DTI of vertebral BM. Mean diffusivity (MD) and fractional anisotropy (FA) of vertebral BM was calculated and correlated with genotyping, chitotriosidase, hemoglobin (HB) and, platelet count. RESULTS: There was a statistically significant difference in MD and FA of BM between patients and controls (P = 0.001 and 0.02). The area under the curve (AUC) of MD and FA used to differentiate untreated patients from controls was 0.902 and 0.68 with sensitivity, specificity, and, accuracy 92%, 84.6%, and, 89.5% respectively. There was a significant difference in MD and FA of BM between untreated and treated patients (P = 0.001 and 0.02). AUC of MD and FA used to differentiate untreated from treated patients was 0.93 and 0.649 with sensitivity, specificity, and accuracy of 92%, 80%, and 86% respectively. There was a significant difference in MD and FA (P = 0.03, 0.001 respectively) of BM in GD with homozygous L444P mutation (n = 9) and other mutations (n = 14). Chiotriptase, HB and platelet count of patients was correlated with MD (r = -0.36, 0.42, -0.41) and FA (r = -0.47, -0.37, -0.46) respectively. CONCLUSION: DTI of vertebral BM can help in diagnosis and monitoring patients with GD after therapy and correlated with genotyping, and hematological biomarkers of GD.

EEG abnormalities in patients with chronic neuronopathic Gaucher disease: A retrospective review.

The clinical phenotype of Gaucher disease type 3 (GD3), a neuronopathic lysosomal storage disorder, encompasses a wide array of neurological manifestations including neuro-ophthalmological findings, developmental delay, and seizures including progressive myoclonic epilepsy. Electroencephalography (EEG) is a widely available tool used to identify abnormalities in cerebral function, as well as epileptiform abnormalities indicating an increased risk of seizures. We characterized the EEG findings in GD3, reviewing 67 patients with 293 EEGs collected over nearly 50 years. Over 93% of patients had some form of EEG abnormality, most consisting of background slowing (90%), followed by interictal epileptiform discharges (IEDs) (54%), and photoparoxysmal responses (25%). The seven patients without background slowing were all under age 14 (mean 6.7 years). There was a history of seizures in 37% of this cohort; only 30% of these had IEDs on EEG. Conversely, only 56% of patients with IEDs had a history of seizures. These observed EEG abnormalities document an important aspect of the natural history of GD3 and could potentially assist in identifying neurological involvement in a patient with subtle clinical findings. Additionally, this comprehensive description of longitudinal EEG data provides essential baseline data for understanding central nervous system involvement in neuronopathic GD.

Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

99mTc-MDP Bone Scintigraphy in Gaucher Disease.

In this case report, we present the bone scintigraphic findings of a 9-year-old boy with Gaucher disease who has a history of fractures to evaluate the extent of his osseous lesions. Gaucher disease is a genetic deficiency of lysosomal enzyme glucocerebrosidase, which results in the accumulation of glucocerebroside in the macrophages in the reticuloendothelial cells of the spleen, liver, and bone marrow. Most patients with type 1 Gaucher disease present a clinical or radiographic evidence of infiltrative bone disease. Lipid-filled macrophages called Gaucher cells infiltrate the bone marrow, leading to medullary expansion, diffuse osteoporosis, ischemic necrosis, and fractures.

Enhanced vertebra to disk ratio as a new semi-quantitative imaging biomarker for Gaucher disease patients.

PURPOSE: Gaucher disease (GD) is an inherited lysosomal storage disorder. The Vertebral Disk Ratio (VDR) is a semi-quantitative imaging biomarker designed to diagnose and monitor GD. Computed from standard T1 MRI images, the VDR is derived from 2D segmentations. This study aimed to evaluate the 3D version of VDR, namely eVDR, and analyze the performances of two eVDR-derived response criteria for GD patients. METHODS: Three datasets were used: 8 longitudinal GD patients, 13 non-GD patients, and 2 longitudinal GD patients with known Bone Marrow Burden (BMB) scores. Two eVDR-derived response criteria were tested: 1) a parametric version (PeVDR) averaging all eVDR measures recorded for the 5 lumbar vertebrae; and 2) a non-parametric version (NPeVDR), considering all eVDR measures as independent and evaluating therapeutic response in a paired fashion. Analyses included assessment of reader variability in eVDR (3D) versus VDR (2D) and comparison with BMB response criteria. RESULTS: The repeatability of eVDR (3D) versus VDR (2D) demonstrated no difference in mean values but a lower variance (p < 0.004). The PeVDR intra-reader variability had a standard deviation < 0.1 with a coefficient of variation < 5%; the inter-reader variability featured a Limit of Agreement < 5% and a Bias < 3%. Observational comparison of eVDR and BMB scoring and sensitivity indicated a correlation between PeVDR and BMB, with an improved sensitivity with the NPeVDR version. CONCLUSIONS: Based on a standard MRI sequence, the eVDR imaging biomarker and its derived response criteria improved GD assessments and could help assessing other bone marrow diseases.

Acoustic radiation force impulse point shear wave elastography of the liver and spleen in patients with Gaucher disease type 1: Correlations with clinical data and markers of disease severity.

PURPOSE: To evaluate the feasibility of acoustic radiation force impulse point shear wave elastography (ARFI-pSWE) of the liver and spleen in patients with Gaucher disease type 1 (GD1), and to assess correlations between organ stiffness and clinico-radiologic data, particularly the GD1 Severity Scoring System (GD-DS3). MATERIALS AND METHODS: We retrospectively evaluated the results of ARFI-pSWE as measures of liver and spleen stiffness in 57 patients with GD1. The feasibility of the method was assessed. Correlations between elastography data and clinical data related to the metabolic syndrome, laboratory tests, and GD1-related clinico-radiologic data (bone marrow burden score, GD-DS3) were assessed. RESULTS: ARFI-pSWE provided reliable results (i.e. standard deviation <30% of the mean value between the measurements) in 50/57 patients. Significant liver fibrosis was present in 35/50 patients (70%). Liver stiffness significantly correlated with GD-DS3 score (p = .03), and number of fulfilled criteria of metabolic syndrome (p = .03). Spleen stiffness significantly correlated with age (p = .021), body mass index (p = .002), number of fulfilled criteria of metabolic syndrome (p = .02), and several laboratory parameters (alanine aminotransferase, gamma glutamyltranspeptidase, triglycerides, cholesterol), and nearly significantly with GD-DS3 score (p = .059). CONCLUSION: ARFI-pSWE is a useful tool for a more detailed assessment of disease severity in patients with GD1, which adds relevant information to the standard clinical scores. Thus, elastography might allow for extended therapy monitoring, especially in patients with significant liver fibrosis. Spleen elastography showed promising results; thus, its role should be further investigated.

Gaucher disease status and treatment assessment: pilot study using magnetic resonance spectroscopy bone marrow fat fractions in pediatric patients.

OBJECTIVE: To assess magnetic resonance spectroscopy (MRS) bone marrow fat fractions' ability to discern between untreated Gaucher disease patients and healthy controls based on assessment of bone marrow infiltration and evaluate response to enzyme replacement therapy (ERT) on serial imaging. METHODS: This retrospective case-controlled study compared conventional MRI and bone marrow MRS findings in six pediatric and young adult Gaucher disease patients with age- and sex-matched controls, examining femoral neck and lumbar spine bone marrow fat fractions and bone marrow burden (BMB) scores. Separate analysis of six patients with serial imaging on ERT was performed with analysis of fat fractions, BMB scores, organ volumes, and serum chitotriosidase. RESULTS: Untreated patients had significantly lower femoral and lumbar spine fat fractions than controls (0.32 versus 0.67, p = 0.041 and 0.17 versus 0.34, p = 0.041, respectively). Total BMB scores were significantly higher in patients (8.0 versus 3.5, p = 0.015). In patients on ERT with average follow-up of 3.5 years, femoral neck fat fraction was the sole significant predictor of treatment duration (R square: 0.804, p < 0.001) when adjusted for age. Femoral neck fat fraction also correlated with lumbar spine fat fraction, liver volume and chitotriosidase (p < 0.05). MRS test-retest reliability was excellent (Pearson correlations: 0.96, 0.99; p-values <0.001). BMB inter-rater reliability was good overall with an intra-class correlation coefficient of 0.79 for total score, although lumbar spine score reliability was poor at 0.45. CONCLUSION: MRS-derived bone marrow fat fractions appear capable of detecting Gaucher disease severity and monitoring treatment-related changes as a predictor of ERT duration in pediatric and young adult patients.

Longitudinal Positron Emission Tomography of Dopamine Synthesis in Subjects with GBA1 Mutations.

Mutations in GBA1, the gene mutated in Gaucher disease, are a common genetic risk factor for Parkinson disease, although the penetrance is low. We performed [18 F]-fluorodopa positron emission tomography studies of 57 homozygous and heterozygous GBA1 mutation carriers (15 with parkinsonism) and 98 controls looking for early indications of dopamine loss using voxelwise analyses to identify group differences in striatal [18 F]-fluorodopa uptake (Ki ). Forty-eight subjects were followed longitudinally. Cross-sectional and longitudinal comparisons of Ki and Ki change found significant effects of Parkinson disease. However, at baseline and over time, striatal [18 F]-fluorodopa uptake in mutation carriers without parkinsonism did not significantly differ from controls. ANN NEUROL 2020;87:652-657.