Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

Application of Seasonal Auto-regressive Integrated Moving Average Model in Forecasting the Incidence of Hand-foot-mouth Disease in Wuhan,China

Outbreaks of hand-foot-mouth disease（HFMD） have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average（ARIMA） model for time series analysis was designed in this study. Eighty-four-month（from January 2009 to December 2015） retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination（R^2）, normalized Bayesian Information Criterion（BIC） and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as（1,0,1）（0,1,1）12, with the largest coefficient of determination（R^2=0.743） and lowest normalized BIC（BIC=3.645） value. The residuals of the model also showed non-significant autocorrelations（P_（Box-Ljung（Q））=0.299）. The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.

Effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease

Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of 116 children with hand-foot-mouth disease who were treated in this hospital between September 2016 and February 2018 were selected as the study subjects and divided into the control group (n=58) and the Potassium Sodium Dehydroandrograpolide Succinate group (n=58) by random number table method. Control group received symptomatic + interferon therapy, and Potassium Sodium Dehydroandrograpolide Succinate group received symptomatic + interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy, and they were treated for 1 week. The differences in the serum contents of inflammatory factors, adhesion molecules and humoral immunity indexes were compared between the two groups before and after treatment. Results:Before treatment, serum levels of inflammatory factors, adhesion molecules and humoral immunity indexes were not significantly different between the two groups. After 1 week of treatment, serum inflammatory factors IL-1β, IL-10, PCT and hs-CRP levels of Potassium Sodium Dehydroandrograpolide Succinate group were lower than those of control group;serum adhesion molecules CD44, ICAM-1 and VCAM-1 levels were lower than those of control group;serum humoral immunity indexes IgA, IgG, C3 and C4 levels were lower than those of control group. Conclusion: Interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy can effectively reduce the systemic inflammatory response and improve the humoral immune function in children with hand-foot-mouth disease.

Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application

Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were randomly divided into control group(n=30),treatment group(n=30)and control group(n=30).The control group was treated with routine western medicine,the treatment group 1 was treated with oral antelope horn powder on the basis of control group,the second group was treated with auricular point application on the basis of treatment group 1,and the time of symptom relief and clinical cure were observed in each group.Related immune function and related inflammatory factors,serum neuron-specific enolase(NSE),safety index.Results:In treatment group 1,the time of herpes regression,antipyretic,antispasmodic time and clinical cure time were shorter than those of control group,and the time of treatment 2 group was shorter than that of group 1(P<0.05).The levels of CD3,CD4 and CD8 were increased after treatment in the three groups,especially in the treatment group(P<0.05),and the levels of TNF-毩αand IL-2,IL-6,IL-10 were decreased after treatment in the three groups,especially in the treatment group(P<0.05).NSE decreased after treatment in three groups,especially in treatment group 2(P<0.05).Conclusion:The application of antelope horn powder combined with auricular point application can obviously improve the severe hand,foot and mouth disease,and the clinical curative effect is definite.It is worth popularizing and applying in clinical practice.

Correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease complicated by encephalitis

Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were diagnosed with hand-foot-mouth disease in Yulin Third Hospital between May 2015 and February 2017 were selected, children who were combined with central nervous system were selected as severe group, and children who were not combined with central nervous system were selected as mild group;children who received physical examination during the same period were selected as the control group. Serum was collected to determine the contents of NSE, S100β and inflammatory response mediators, and peripheral blood was collected to determine the contents of T cell subsets and NK cells.Results: Serum NSE and S100β levels of severe group and mild group were significantly higher than those of control group, and serum NSE and S100β levels of severe group were significantly higher than those of mild group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group and mild group were significantly higher than those of control group while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of control group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group were significantly higher than those of mild group and positively correlated with NSE and S100β levels while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of mild group and negatively correlated with NSE and S100β levels.Conclusion: The increase of serum NSE and S100β levels in children with HFMD complicated by encephalitis is closely related to inflammatory response activation and immune response disorder.

陕西省蒲城县2009至2013年手足口病流行特征分析

目的：分析陕西省手足口病高发区蒲城县手足口病的流行和发展趋势，为制定预防控制策略提供科学依据。方法用描述性流行病学方法对蒲城县2009至2013年手足口病疫情资料进行分析。结果蒲城县2009至2013年累计报告手足口病8712例，年均报告发病率223．78/10万。每年4至7月和9至11月为手足口病高发季节，发病数分别占发病总数的59．52％和29．81％；儿童0～5岁为高发年龄，发病数占发病总数的96．14％。男性年均报告发病率为271．22/10万，女性为195．29/10万，男性发病率高于女性。实验室诊断病例中肠道病毒71型感染占77．19％。中部台塬区发病率为252．01/10万，高于北部山原沟壑区和南部平原区。不同地区间病原学差异无统计学意义（确切概率P＝0．564）。结论蒲城县手足口病具有明显的季节性高发特点，5岁以下儿童为手足口病高危人群，应持续重点加强农村地区的健康教育和卫生宣传，引导群众及早就医，并坚持隔离，从而达到有效控制疫情。

Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease

It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn&#x02019;s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.

Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

Graft-versus-host disease after liver transplantation:A comprehensive literature review

AIM： To determine the factors affecting mortality in pa- tients who developed graft-versus-host disease （GvHD） after liver transplantation （LT）. METHODS： We performed a review of studies of GvHD following LT published in the English literature and ac- cessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phras- es, 88 articles were identified. Of these, 62 articles con- raining most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association （P 〈 0.05） were then sub- jected to multivariate analyses using a Cox proportional- hazards model. RESULTS： The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years （range： 8 mo to 74 years）, who met the inclusion criteria for the present study. Deaths occurred in 59 （67.8%） patients, whereas 28 （32.2%） survived after a mean follow-up period of 280.8 ± 316.2 d （range： 27-2285 d）. Among the most frequent symptoms were rash （94.2%）, fever （66.6%）, diarrhea （54%）, and pancytopenia （54%）. The average time period between LT and first symptom on- set was 60.6 ± 190.1 d （range： 2-1865 d）. The Kaplan- Meier analysis revealed that pancytopenia （42.8% vs 59.3%, P = 0.03）, diarrhea （39.2% vs 61.0%, P = 0.04）, age difference between the recipient and the donor （14.6 ± 3.1 years vs 22.6 ± 2.7 years, P 〈 0.0001）, and time From first symptom occurrence to diagnosis or treatment （13.3 ± 2.6 mo vs 15.0 ± 2.3 mo, P 〈 0.0001） were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, de- termined that an age difference between the recipient and donor was an independent risk Factor （P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7）. CONCLUSION： This study showed that an age differ- ence between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.

Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis

The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportinand the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH. More defined studies are required to improve our understanding of these effects.

Clinical applications of hepatocyte transplantation

The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with lifethreatening liver diseases dying while on the waiting list. The use of cell transplantation for liver disease is an attempt to correct metabolic defects, or to support liver function as a bridge to liver transplantation and, as such, has raised a number of expectations. Most of the available studies briefly reported here focus on adult hepatocyte transplantation (HT), and the results are neither reproducible nor comparable, because the means of infusion, amount of injected cells and clinical variability differ among the studies. To better understand the specif ic role of HT in the management of end-stage liver disease, it is important that controlled studies, designed on the principles of evidence-based medicine, be done in order to guarantee the reproducibility of results.

Quality of ulcer healing in gastrointestinal tract:Its pathophysiology and clinical relevance

In this paper, we review the concept of quality of ulcer healing （QOUH） in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease （PUD） has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori （H. pylorl~, which is also the cause of ulcer recur- rence. However, H. pylori-negative ulcers are pres- ent in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macro- phages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer re- currence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a defi- ciency and/or an imbalance of endogenous growth fac- tors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn＇s disease and ulcer- ative colitis.

Prophylaxis of chronic kidney disease after liver transplantation-experience from west China

AIM： TO evaluate the prophylaxis of chronic kidney dis- ease （CKD） after liver transplantation （LT） with low-dose calcineurin inhibitor （CNI） and mycophenolate mofetil （MMF）.

Human immunodeficiency virus infection and the liver

Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.

Clinical significance of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains unclear.Although OBI has been well documented in human immunodeficiency virus(HIV) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIV setting.

Clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in China

BACKGROUND： Hand-foot-mouth disease has become a major public health issue in children in China. In the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with NPE caused by enterovirus 71.METHODS： The study was conducted in 2 pediatric intensive care units （PICUs） over a 2-month period. Clinical records were reviewed of critically ill children with severe encephalitis associated with NPE caused by EV71 who were admitted to PICUs during the period of May to June 2008 in Fuyang.RESULTS： We reviewed the complete records of 36 children, of whom 23 （63.9%） were male and 13 （36.1%） female. Their age ranged from 4 to 48 months, with an average of 15.8 months. All children except one were under 3 years of age. The overall mortality in these children was 19.4%. The average duration of critical life threatening signs and symptoms was 2.1 days （12 hours-5 days）. Nervous system diseases included brainstem encephalitis in 27 children （75%）, brainstem encephalitis associated with myelitis in 6 children （16.7%）, and general encephalitis in 3 chidren （8.3%）, respectively. In 12 patients of NPE （33.3%） pink or bloody bubble sputum and asymmetric pulmonary edema or hemorrhage was the primary manifestation but no typical exanthema was observed. Five children died of acute onset of NPE and / or pulmonary hemorrhage with rapid progression of cardiopulmonary failure within hours after admission. Therapeutic management consisted of mechanical ventilation and administration of mannitol, methylprednisolone, intravenous immunoglobulin （IVIG） and vasoactive drugs, associated with the need of fluid volume resuscitation in 9 （25%） of the 36 children.CONCLUSION： In children less than 3 years of age found to be affected by severe EV71 encephalitis associated with NPE, one fifth may die. The major organ systems infected by severe EV71 include the central nervous system, the respiratory system, and the cardiovascular system. Early diagnosis and evaluation, respiratory support, treatment of intracranial hypertension, and mainttenance of function of the cardiovascular system are the most important therapeutic measures.

Relationship between Serum TSH Level with Obesity and NAFLD in Euthyroid Subjects

To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects,1322 subjects were sub-jected to a questionnaire survey and physical examination.Fasting blood samples were collected to test serum TSH,plasma glucose and lipids.Fatty liver was diagnosed by type B ultrasonography.The rela-tionship between serum TSH level and body mass index (BMI),percentage of body fat and NAFLD was analyzed.The results showed that serum TSH level was significantly higher in females than in males at the same group,and it was significantly higher in overweight group than in control group.Levels of body weight,BMI,waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women.However,plasma lipids showed no significant differences.In males all the parameters showed no significant differences between two groups.Serum TSH was sig-nificantly correlated with body weight,BMI,waist circumference and percentage of body fat after ad-justment for age in females.Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH.Serum TSH level was significantly higher in non-alcoholic fatty liver group than in normal group in females.Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD.Taken together the data suggest that se-rum TSH in normal range is significantly correlated with BMI and percentage of body fat in females.And the change of TSH level would not influence the prevalence of NAFLD.

Tracheobronchial nodules and pulmonary infiltrates in a patient with Crohn's disease

Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.

Imaging of gaucher disease

Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of the enzyme glucocerebrosidase.This leads to he-matologic,visceral and skeletal maifestions.Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly.The normal bone marrow is re-placed by the accumulating substrate leading to many of the hematologic signs including anemia.The visceral and skeletal manifestations can be visualized with vari-ous imaging modalities including radiography,com-puted tomography,magnetic resonance imaging(MRI)and radionuclide scanning.Prior to the development of enzyme replacement therapy,treatment was only sup-portive.However,once intravenous enzyme replace-ment therapy became available in the 1990s it quickly became the standard of care.Enzyme replacement therapy leads to improvement in all manifestations.Thevisceral and hematologic manifestations respond more quickly usually within a few months or years.The skel-etal manifestations take much longer,usually several years,to show improvement.In recent years newer treatment strategies,such as substrate reduction thera-py,have been under investigation.Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.