Effects Of Enzyme Replacement Therapy Research Articles

Is it necessary to correct the intestinal microbiota disorders in chronic pancreatitis?

The frequency of intestinal microbiota disorders in patients with chronic pancreatitis (CP) is extremely high and can reach 97%. The bacterial overgrowth syndrome (SIBO) and the syndrome of increased epithelial permeability (SPEP), developing against the background of excretory insufficiency of the pancreas, affect the severity of the clinical picture of the disease, reduce the effectiveness of enzyme replacement therapy and generally contribute to the further progression of CP.The article presents a modern view on the mechanisms of the formation of SIBO and SPEP in CP. There is their aggravating effect on the course of the disease and the aggravation of disorders of the digestive and absorption processes that accompany them is shown and analyzed in the article.For decontamination of conditionally pathogenic and pathogenic flora, increasing the number and metabolic activity of indigenous microflora in patients with CP, the use of a non-absorbable broad-spectrum antibiotic rifaximin is effective. In order to restore the barrier function of the gastrointestinal mucosa, the drug of choice is rebamipid, a universal cytoprotector that affects all three levels of epithelial tissue protection (preepithelial, epithelial and subepithelial).Conclusion. CP is characterized by the complexity of its etiology and pathogenesis. Bacterial factors, in particular, SIBO and SPEP, play an essential role in the development of inflammatory changes in the pancreas. In the complex therapy of CP, it is advisable to take measures aimed at correcting disorders of the intestinal microbiota.

Fabry Disease and the Effectiveness of Enzyme Replacement Therapy (ERT) in Left Ventricular Hypertrophy (LVH) Improvement: A Review and Meta-Analysis.

Background: Fabry disease is an inherited lysosomal storage disease affecting multiple organs with complications, including cardiomyopathy such as left ventricular hypertrophy (LVH). Enzyme replacement therapy (ERT) has been the main treatment for Fabry patients since 2001. However, the indications of ERT are not clearly defined. We performed a meta-analysis according to previous studies to review the benefit of ERT for LVH improvement in Fabry patients.Methods: We performed a literature search from the National Center for Biotechnology Information (NCBI) and PubMed database without restriction of years for systematic review purposes. We performed a systematic review of clinical cohort studies and trials using a pooled analysis of proportions. We calculated the pooled proportions and the confidence intervals (CI) for left ventricular mass index (LVMI) for both ERT treatment and ERT treatment-naïve groups. The results for before ERT treatment and after ERT treatment are also investigated.Results: A total of 5 cohort studies and 2 randomized controlled trials (RCTs), involving a total of 552 participants (267 on ERT treatment versus 285 on naïve treatment), met the inclusion criteria. The pooled proportions analysis showed that the difference in means of LVMI between the ERT treatment group and the ERT treatment-naïve group was -0.149 [95% CI: -0.431, 0.132]. Effect differences favored the ERT treatment group over the ERT treatment-naïve group (p = 0.034). Another analysis included 3 cohort studies and 1 RCT with 442 participants (228 on before ERT and 214 on 4 years after ERT). The pooled proportions analysis showed that the difference in means of LVMI between the before ERT treatment group and the after ERT treatment group was -0.448 [95% CI: -0.787, -0.108]. It favored the 4 years after ERT group over the before ERT group (p = 0.037).Conclusions: Based on the currently available data, our meta-analysis showed that there are beneficial effects on LVH improvement with ERT in Fabry disease patients. It is better to start ERT as soon as we have diagnoses in female carriers and atypically affected males. Further research is needed to investigate the role of ERT in LVH improvement.

Evaluation of endocrine functions before and after enzyme replacement therapy in children with mucopolysaccharidosis

There is a scarcity of data concerning endocrine function and the effects of enzyme replacement therapy (ERT) on growth and other endocrine functions in patients with mucopolysaccharidosis (MPS). This study retrospectively evaluated height increase, bone mineral density (BMD), and other endocrine functions in MPS patients who received ERT for at least two years in our clinic. The clinical findings, hormonal analysis (TSH, fT4, ACTH, cortisol, FSH, LH, testosterone, estradiol, prolactin, GH, IGF-1, IGFBP-3), and BMD measurements of 10 MPS patients, aged 0-18 years, before and after ERT were recorded and compared retrospectively. Four patients were MPS Type-2, five were MPS Type-4, and one was MPS Type-6. Nine of the patients were male, and one was female. The mean treatment onset age was 7.6 years. The mean ± standard deviation of the patients' height SDS was -4.61±3.01 before treatment and -5.65±2.42 after treatment. While the mean BMD Z-score of the patients was -2.33±1.77 before treatment, it was -0.94±1.52 after treatment. Apart from growth retardation (one of the most prominent disease features), no severe dysfunction was detected in other endocrine organs in our patients with MPS. Severe short stature was evident at the time of diagnosis in MPS patients, and their height SDS worsened, despite ERT. However, osteoporotic BMD Z-scores at diagnosis improved after ERT. No serious dysfunction was seen in other endocrine organs.

New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside.

Background: There are new emerging phenotypes in Pompe disease, and studies on smooth muscle pathology are limited. Gastrointestinal (GI) manifestations are poorly understood and underreported in Pompe disease. Methods: To understand the extent and the effects of enzyme replacement therapy (ERT; alglucosidase alfa) in Pompe disease, we studied the histopathology (entire GI tract) in Pompe mice (GAAKO 6neo/6neo). To determine the disease burden in patients with late-onset Pompe disease (LOPD), we used Patient-Reported Outcomes Measurements Information System (PROMIS)-GI symptom scales and a GI-focused medical history. Results: Pompe mice showed early, extensive, and progressive glycogen accumulation throughout the GI tract. Long-term ERT (6 months) was more effective to clear the glycogen accumulation than short-term ERT (5 weeks). GI manifestations were highly prevalent and severe, presented early in life, and were not fully amenable to ERT in patients with LOPD (n = 58; age range: 18–79 years, median age: 51.55 years; 35 females; 53 on ERT). Conclusion: GI manifestations cause a significant disease burden on adults with LOPD, and should be evaluated during routine clinical visits, using quantitative tools (PROMIS-GI measures). The study also highlights the need for next generation therapies for Pompe disease that target the smooth muscles.

Dental effects of enzyme replacement therapy in case of childhood-type hypophosphatasia

BackgroundHypophosphatasia (HPP), a skeletal disease characterized by hypomineralization of bone and teeth, is caused by an ALPL gene mutation that leads to low activity of the tissue non-specific alkaline phosphatase enzyme. Although enzyme replacement therapy (ERT) was recently introduced for affected patients, no known studies have been reported regarding its dental effects related to permanent teeth and jaw bones. In the present study, we examined the dental effects of ERT in a case of childhood-type hypophosphatasia, including panoramic radiography findings used to estimate the dental age of permanent teeth and mandibular bone density. Furthermore, the effects of that therapy on the periodontal condition of the patient were evaluated by comparing periodontal pocket depth before and after initiation.Case presentationAn 11-year-1-month-old boy was referred to our clinic for consultation regarding oral management. Two primary incisors had spontaneously exfoliated at 1 year 8 months old and he had been diagnosed with childhood-type HPP at the age of 2 years 2 months. Obvious symptoms were localized in the dental region at the time of diagnosis, though later extended to other parts of the body such as bone pain. ERT was started at 11 years 7 months of age, after which bone pain disappeared, and motor functions and activities of daily living improved. We estimated dental age based on tooth development stage. The age gap between chronological and dental ages was expanded before treatment, and then showed a constant decrease after ERT initiation and finally disappeared. The index for mandibular bone density (mandibular cortical width / length from mesial buccal cusp to apex of first molar) was increased after ERT initiation. Furthermore, the periodontal condition for all teeth except those exfoliated was stable after starting therapy.ConclusionsERT resulted in improved tooth and mandibular bone mineralization, with notably good effects on teeth under formation. Acceleration of mineralization of roots associated with erupting teeth leads to stabilization of the periodontal condition. We concluded that ERT contributed to the improved dental condition seen in this patient.

MO017THERAPEUTICAL POTENTIAL OF ENZYME REPLACEMENT: NEW INSIGHTS AND PERSPECTIVES IN HUMAN ENDOTHELIAL CELLS TREATED WITH CHLOROQUINE

Background and AimsCOVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. The study aims to investigate in vitro the effect of enzyme replacement therapy (ERT) in chloroquine-induced endothelial dysfunction.MethodWe have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase-β). Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy.ResultsChloroquine significantly induced the accumulation of acid organelles (P<0.05), increased ROS levels, and decreased NO production (P<0.05), in vitro. These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P<0.05).ConclusionChloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.

Effect of enzyme replacement therapy on Fabry cardiomyopathy: evaluation of cardiac function is more useful than structural evaluation.

Effect of enzyme replacement therapy on Fabry cardiomyopathy: evaluation of cardiac function is more useful than structural evaluation.

Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series

BackgroundThis case series includes longitudinal clinical data of ten patients with Morquio A syndrome from south and southeastern parts of Turkey, which were retrospectively collected from medical records. All patients received enzyme replacement therapy (ERT). Clinical data collected included physical appearance, anthropometric data, neurological and psychological examinations, cardiovascular evaluation, pulmonary function tests, eye and ear-nose-throat examinations, endurance in the 6-min walk test and/or 3-min stair climb test, joint range of motion, and skeletal investigations (X-rays, bone mineral density).ResultsAt the time of ERT initiation, two patients were infants (1.8 and 2.1 years), five were children (3.4–7.1 years), and three were adults (16.5–39.5 years). Patients had up to 4 years follow-up. Most patients had classical Morquio A, based on genotypic and phenotypic data. Endurance was considerably reduced in all patients, but remained relatively stable or increased over time in most cases after treatment initiation. Length/height fell below normal growth curves, except in the two infants who started ERT at ≤ 2.1 years of age. All patients had skeletal and/or joint abnormalities when ERT was started. Follow-up data did not suggest improvements in skeletal abnormalities, except in one of the younger infants. Nine patients had corneal clouding, which resolved after treatment initiation in the two infants, but not in the other patients. Hepatomegaly was reported in seven patients and resolved with treatment in five of them. Other frequent findings at treatment initiation were coarse facial features (N = 9), hearing loss (N = 6), and cardiac abnormalities (N = 6). Cardiac disease deteriorated over time in three patients, but did not progress in the others.ConclusionsOverall, this case series with Morquio A patients confirms clinical trial data showing long-term stabilization of endurance after treatment initiation across ages and suggest that very early initiation of ERT optimizes growth outcomes.

Natural progression of cardiac features and long-term effects of enzyme replacement therapy in Taiwanese patients with mucopolysaccharidosis II

BackgroundCardiac abnormalities have been observed in patients with mucopolysaccharidosis type II (MPS II). The aim of this study was to investigate the cardiac features and natural progression of Taiwanese patients with MPS II, and evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function.MethodsThe medical records and echocardiograms of 48 Taiwanese patients with MPS II (median age, 6.9 years; age range, 0.1–27.9 years) were reviewed. The relationships between age and each echocardiographic parameter were analyzed.ResultsThe mean z-scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter were 1.10, 2.70, 0.95 and 1.91, respectively. Z scores > 2 were identified in 33%, 54%, 13%, and 46% for LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (MR) (56%), followed by aortic regurgitation (AR) (33%). The severity of mitral stenosis (MS), MR, aortic stenosis (AS), AR, and the existence of valvular heart disease were all positively correlated with increasing age (p < 0.01). We also compared the echocardiographic parameters between two groups: (1) 12 patients who had up to 17 years of follow-up echocardiographic data without ERT, and (2) nine patients who had up to 12 years of follow-up data with ERT. The results showed that z-score changes of LVMI significantly improved in the patients who received ERT compared to those who did not receive ERT (0.05 versus 1.52, p < 0.05). However, the severity score changes of MS, MR, AS, and AR all showed gradual progression in both groups (p > 0.05).ConclusionsHigh prevalence rates of valvular heart disease and cardiac hypertrophy were observed in the MPS II patients in this study. The existence and severity of cardiac hypertrophy and valvular heart disease in these patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS II appeared to be effective in stabilizing or reducing the progression of cardiac hypertrophy, but it only had a limited effect on valvulopathy.

Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy.

Background: Cardiovascular abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular regurgitation and stenosis and cardiac hypertrophy. Only a few studies have focused on aortic root dilatation and the long-term effects of enzyme replacement therapy (ERT) in these patients. Methods: We reviewed echocardiograms of 125 Taiwanese MPS patients (age range, 0.1 to 19.1 years; 11 with MPS I, 49 with MPS II, 25 with MPS III, 29 with MPS IVA, and 11 with MPS VI). The aortic root diameter was measured at the sinus of Valsalva. Results: Aortic root dilatation (z score >2) was observed in 47% of the MPS patients, including 66% of MPS IV, 51% of MPS II, 45% of MPS VI, 28% of MPS III, and 27% of MPS I patients. The mean aortic root diameter z score was 2.14 (n = 125). The patients with MPS IV had the most severe aortic root dilatation with a mean aortic root diameter z score of 3.03, followed by MPS II (2.12), MPS VI (2.06), MPS III (1.68), and MPS I (1.03). The aortic root diameter z score was positively correlated with increasing age (n = 125, p < 0.01). For the patients with MPS II, III, and IV, aortic root diameter z score was also positively correlated with increasing age (p < 0.01). For 16 patients who had received ERT and had follow-up echocardiographic data (range 2.0–16.2 years), the mean aortic root diameter z score change was −0.46 compared to baseline (baseline 2.49 versus follow-up 2.03, p = 0.490). Conclusions: Aortic root dilatation was common in the patients with all types of MPS, with the most severe aortic root dilatation observed in those with MPS IV. The severity of aortic root dilatation worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS appears to stabilize the progression of aortic root dilatation.

Stroke and Fabry Disease: A Review of Literature.

Fabry disease is an X-linked lysosomal storage disorder caused by a mutation in the alpha-galactosidase A (GLA) gene, leading to the deficiency of alpha-galactosidase A enzyme. The natural history of the affected patients (both males and females) includes neurovascular complications, such as cerebrovascular disease at a relatively young age. The pathophysiology behind the vascular involvement is primarily attributed to the accumulation of globotriaosylceramide and its derivatives in the vascular endothelium and vascular smooth muscle cells. MRI is the gold standard radiological investigation to detect the white matter lesions characteristic of Fabry disease's neurological involvement. More studies should focus on the utility of universally screening patients with young stroke for Fabry disease and the effectiveness of enzyme replacement therapy to prevent stroke. This review offers a synopsis of the current knowledge of the pathophysiology, neuroradiology, treatment, and prognosis of cerebrovascular disease in Fabry patients.

Оцінка ефективності замісної ферментної терапії зовнішньосекреторної недостатності підшлункової залози у хворих на цукровий діабет та хронічний панкреатит

The study of the combined course of chronic pancreatitis and diabetes mellitus present a particular interest. The purpose of the study was to determine the effectiveness of correction of exocrine pancreatic insufficiency of the pancreas in patients with chronic pancreatitis and diabetes mellitus types 1 and 2 with using of different forms and doses of polyenzyme drugs. Material and methods. 126 patients with diabetes mellitus and chronic pancreatitis were examined. The patients were divided into 2 groups: 1 group included 62 patients with type 1 diabetes mellitus, and 2 group comprised 64 patients with type 2 diabetes. All surveyed patients underwent general clinical, anthropometric, instrumental and laboratory methods of investigation. Patients of both groups were divided into subgroups depending on the method of correction of exocrine pancreatic insufficiency, namely 1.1 and 2.1 subgroups received tableted polyenzyme preparation with minimal lipase activity of 10000 IU as enzyme therapy, and 1.2 and 2.2 subgroups received mini-tableted polyenzyme preparation with minimal lipase activity of 25000 IU. Results and discussion. The use of mini-tableted polyenzyme preparation with minimal lipase activity of 25000 IU according to the results of C13-mixed triglyceride and C13-amylase breath tests was an effective method for the correction of exocrine insufficiency of the pancreas in patients with chronic pancreatitis and diabetes mellitus types 1 and 2. We detected a statistically significant increase of the maximally concentration of 13CO2 between 150 and 210 minutes of the study (up to 9.2±0.4% 1.2 subgroup and up to 9.7±0.5% in patients 2.2 subgroup), as well as the total concentration of 13CO2 in at the end of 360 minutes of the study (up to 19.7±0.6% and up to 27.3±1.1%) according to the results of C13-mixed triglyceride breath tests, p&lt;0,05. Conclusion. The use of a mini-tableted polyenzyme preparation with a minimum lipase activity of 25000 IU was a more effective method for correction of exocrine pancreatic insufficiency in patients with chronic pancreatitis and type 1 and 2 diabetes mellitus, than using a tableted polyenzyme preparation in a dose of 20000 IU per main meal. The study results showed that using C13-mixed triglyceride and C13-amylase breath test were highly informative methods for evaluating the effectiveness of enzyme replacement therapy in exocrine pancreatic insufficiency in patients with chronic pancreatitis and type 1 and 2 diabetes. The use of a mini-tablet polyenzyme drug in patients with chronic pancreatitis and type 1 and 2 diabetes mellitus is an effective means to normalize the manifestations of malabsorption in terms of α1-antitrypsin clearance

Cardiac manifestations and effects of enzyme replacement therapy for over 10 years in adults with the attenuated form of mucopolysaccharidosis type I

BackgroundMucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme α-L-iduronidase. Cardiac manifestations such as valvular heart disease are associated with poor prognosis. There have been only a few reports on the effect of long-term enzyme replacement therapy (ERT) for adult patients with the attenuated form of MPS I (Scheie syndrome) and cardiac involvement. MethodsWe retrospectively reviewed four adult patients of Scheie syndrome for which ERT was performed in our hospital. We investigated the findings of electrocardiography and echocardiography for the four patients performed before and 10 years after the initiation of ERT to evaluate the efficacy for ERT in Scheie syndrome. ResultsThe ages of the patients at the initiation of ERT ranged from 26 to 46 years. The mean follow-up period was 129 months (121 to 134 months). Two patients underwent valve replacement surgery before the initiation of ERT. One patient had gradual progressive aortic valve stenosis and mitral valve stenosis during the course of ERT, and double valve replacement was finally performed. The patient who had started ERT at the youngest age did not develop significant cardiovascular disease. Regarding clinical courses with ERT for a period of 10 years, all four patients survived and they showed relatively stable cardiac conditions although two patients developed sick sinus syndrome after the valvular surgery. ConclusionsValvular disease in patients with Scheie syndrome occur at a young age. In a limited number of the four patients, ERT might contribute the stability of cardiac condition.

AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.06 Long-term effects of enzyme replacement therapy in an elderly cohort of late-onset Pompe disease patients

First longitudinal studies showed that enzyme replacement therapy (ERT) effects in late-onset Pompe disease (LOPD) seem to peak at 2-3 y often followed by a secondary decline. We aimed to examine long-term ERT effects in an elderly cohort of LOPD. Main inclusion criteria were age at diagnosis and onset of ERT > 50 y and ERT duration > 7 y. Outcome parameters included MRC sum-score (% of max.), 6-minute walk test 6MWT (% predicted), Quick Motor Function Test QMFT (% of max.), forced vital capacity FVC sitting and supine (% predicted), CK levels, and IgG antibody titers against alglucidase alfa. Six patients (3 f/3 m) qualified for the study, all were ambulatory at time of diagnosis. The median age at onset was 49 y (range 40-64), age at diagnosis and start of ERT 63 y (52-69), and age at last outcome 72.5 y (59-80). The median ERT duration was 8 y (7-12). Two patients became wheelchair-dependent. Two females were still able to walk unassisted and did not need noninvasive ventilation at the end of follow-up. There was no association between clinical outcome and genetic data, skeletal muscle histology, residual enzyme activity, and antibody titers. Peak antibody titers ranged from 0 to high with highest titers in best responders. Patients with lower ERT dosages had higher antibody titers. At least 50% of patients initially benefited from ERT. All patients showed a decline in FVC sitting during long-term follow-up, whereas 33% had a stabilization or improvement of FVC supine. 33% showed a stabilization or improvement of muscle strength. In contrast, QMFT deteriorated in 83% over time. However, 6MWT improved in 67% during a median ERT period of 8 y. CK levels continuously decreased in all patients. Best long-term results were seen in 6MWT, FVC supine and MRC sum-scores. Better ERT effects on FVC supine vs. sitting might hint to a preferential long-term effect on diaphragm muscles. In conclusion, ERT effects were heterogeneous but in general beneficial in elderly LOPD patients.

Effects of agalsidase-β administration on vascular function and blood pressure in familial Anderson–Fabry disease

Fabry is an X-linked disorder of glycosphingolipid metabolism that is caused by variants of the GLA gene that codes for α-galactosidase A, leading to lysosomal accumulation of globotriaosylceramide in many cell types. As a result, affected patients manifest with an increased risk of developing ischemic stroke, peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. The protective effects of enzyme replacement therapy (ERT), the milestone in Fabry disease treatment, against globotriaosylceramide (GL-3) accumulation and Fabry disease progression are well known. However, the mechanism of action of ERT is not well understood. Since GL-3 also accumulates in the vascular endothelium, we investigated the effects of agalsidase-β, a recombinant human α-Gal enzyme approved for the treatment of Fabry disease. In this study, vascular function and blood pressure in four adult siblings affected by Fabry disease were evaluated upon agalsidase-β. In all patients, agalsidase-β infusion improves flow-mediated dilation and augmentation index. These changes occurred after the first infusion and were then maintained for the whole period of observation, i.e., 1 year, with more pronounced additional increments in flow-mediated dilation after the second agalsidase-β infusion. Blood pressure was also maintained at optimal levels in all of the patients for the whole period of observation. Our findings show that agalsidase-β administration can improve vascular function in patients suffering from Fabry disease. Changes in flow-mediated dilation and augmentation index persisted for the whole period of observation (1 year), thus suggesting that early substitutive therapy should be promoted in order to protect the cardiovascular system.

Effects of Enzyme Replacement Therapy for Primary Teeth in a Patient with Infantile Hypophosphatasia

Hypophosphatasia (HPP) is a skeletal disorder characterized by hypomineralization of bone, with early exfoliation of primary teeth. Alkaline phosphatase enzyme replacement therapy (ERT) has been shown to improve bone hypomineralization for patients with HPP, although its dental effects are unknown. A 20-month-old Japanese boy diagnosed with infantile HPP was referred to our clinic because of early exfoliation of primary teeth. The patient had been followed by a pediatrician since the age of 3 months, due to slow weight gain. At the age of 12 months, primary incisors showed sudden exfoliation; at the age of 19 months, a diagnosis of HPP was made based on bone and dental manifestations. ERT was initiated at the age of 21 months. The patient demonstrated stable periodontal conditions of primary molars that erupted after initiation of ERT, due to improved alveolar bone and tooth mineralization. Thus, ERT may improve both dental and systemic conditions.

The role of alkaline phosphatase (alp) and γ-glutamyltransferase (ggt) enzymes activities in monitoring the effect of enzyme replacement therapy in children with gaucher disease

To assess the role of γ-Glutamyltransferase (GGT) and alkaline phosphatase (ALP) in the diagnosis of Gaucher disease (GD) and monitoring the response of liver and bone to the treatment with enzyme replacement therapy (ERT).A case-control study was done on 67 children age range from 3-10 years who had Gaucher disease recruited from the Pediatric Department and Unit of rare disease at Al Imamain Al-Kathemeaain medical city,Gastroenterology and Hepatology Teaching Hospital, Children Welfare Hospital Consultation Clinic and Central Child’s Teaching Hospital. The activity of Alkaline Phosphatase (ALP) and γ- GlutamylTransferase (GGT) enzymes were measured in the samples of 67 Gaucher patients who were categorized as newly diagnosed untreated patients (n=9), patients receiving ERT for 3-5 months (n=18) 6-12 months (n=20) and patients receiving ERT for more than one year (n=20) and compared with twenty age-matched control subjects. The data indicated that the levels of both ALP and GGT in GD patients (216.82 ± 64.51, 35.94 ± 7.11; respectively) were significantly higher than those of controls (163.17 ± 49.34, 28.33 ± 3.36; respectively). Levels of ALP showed to return to levels comparable to those of controls after more than one year of treatment, while GGT levels become comparable to controls’ levels within 6-12 months. Negative significant (p&lt;0.05) correlations were obtained between the levels of ALP and GGT activities with the duration of receiving ERT. Receiver Operating Characteristic (ROC) curve results revealed that GGTshowed a higher area under the curve (AUC), sensitivity, and specificity than ALP activities in all studied groups and subgroups.The possibility of using ALP and GGT as supportive diagnostic markers and as powerful markers for the monitoring of the liver and bone improvement with the administration of ERT.

Dilated Cerebral Arteriopathy in Classical Pompe Disease: A Novel Finding

BackgroundIn Pompe disease, glycogen deposition results in an augmentation of blood flow and abnormal remodeling, with resultant weakening of the arterial walls, which may result in pathologic dilatation of the cerebral arteries. This complication is rare in patients with late-onset Pompe disease, but it has not been well-described in infantile-onset Pompe disease. The effect of enzyme replacement therapy on this process is not known. MethodsWe examined clinical and imaging data on two patients who exhibit cerebrovascular arteriopathy: a 14-year-old boy with infantile-onset Pompe disease on enzyme replacement therapy and a 23-year-old woman with late-onset Pompe disease who was also receiving enzyme replacement therapy. ResultsOur 14-year-old patient exhibits cerebrovascular arteriopathy, primarily proximal and vertebrobasilar, while the 23-year-old patient has a more diffuse pattern. The 14-year-old patient is unique because cerebral dolichoectasias have not been described in infantile-onset Pompe disease. The 23-year-old patient is notable given the age and history of enzyme replacement therapy since age 15 years. ConclusionsDilative cerebral arteriopathy in infantile-onset Pompe disease is novel and similarly atypical is the diffuse vascular dilation seen in our young patient with late-onset Pompe disease, both receiving enzyme replacement therapy. We should be cognizant of the risk of cerebrovascular disease in Pompe disease regardless of the disease variant and enzyme replacement therapy status.

Effect of enzyme replacement therapy on the innate and adaptative immune response in patients with Fabry disease: Preliminary results

La enfermedad relacionada con el depósito de IgG4 es una entidad caracterizada por lesiones tumefactas, infiltrado denso linfoplasmocítico con positividad inmunohistoquímica para IgG4, fibrosis estoriforme y, frecuentemente, niveles séricos elevados de IgG4. Puede cursar con afectación multisistémica; sin embargo, la afectación miocárdica, objetivada mediante pruebas de imagen, no ha sido descrita en la literatura médica. Se presenta el caso clínico de un varón afecto de enfermedad relacionada con IgG4 con posible afectación miocárdica, detectada a través de cardiorresonancia magnética, que plantea el diagnóstico diferencial con otras enfermedades como la sarcoidosis y la enfermedad de Fabry, cuyo diagnóstico diferencial es de gran importancia por su repercusión terapéutica.IgG4-related disease is characterized by mass lesions, a dense lymphoplasmacytic infiltrate with immunohistochemical positivity for IgG4, storiform fibrosis and, frequently, elevated serum IgG4 levels. It can be multisystemic; however, myocardial involvement, which is objectively determined by imaging tests, has not been described in the medical literature. We report the case of a man with IgG4-related disease with possible myocardial involvement, detected by cardiac magnetic resonance. This raises the question of a differential diagnosis with other diseases such as sarcoidosis and Fabry disease, the differential diagnosis of which is of great importance due to its therapeutic impact.

Effects of enzyme replacement therapy on bone density in late onset Pompe disease

To assess the prostate cancer (CaP) detection rates of contrast-enhanced, transrectal subharmonic ultrasound imaging (SHI).This IRB-approved study enrolled 55 subjects. The initial 5 subjects were studied for SHI optimization, while the remaining 50 were evaluated with contrast-enhanced sonography using continuous SHI, color, and power Doppler as well as conventional grayscale, continuous color, and power Doppler and SHI combined with maximum flash replenishment. A maximum of 6 directed biopsy cores were obtained from sites of greatest asymmetrical enhancement, followed by spatially distributed cores in a double sextant distribution. Subharmonic time-intensity parameters, including time to peak intensity, peak intensity, and estimated perfusion were also evaluated for each directed biopsy core. Receiver operating characteristic curve analysis and conditional logistic regression were employed to assess the benefit of each modality and the quantitative SHI parameters.Cancer was detected in 22 of 50 subjects. Among subjects with clinically significant CaP (n = 11), targeted cores were more likely to be positive (odds ratio 1.39, P = .02). The majority of patients detected by SHI demonstrated significant CaP (5/8); SHI remained an independent marker of malignancy in a multivariate logistic regression model (P = .027). Receiver operating characteristic curve analysis of imaging findings compared to biopsy results yielded diagnostic accuracies ranging from 0.59 to 0.80 for all imaging modalities with the highest being for quantitative subharmonic perfusion estimates.This first-in-humans study provides a preliminary estimate of the diagnostic accuracy of SHI for detection of clinically significant CaP (up to 80%).