Enzyme Replacement Therapy In Children Research Articles

Allergic reactions to enzyme replacement therapy in children with lysosomal storage diseases and their management.

Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.

P322 A quality improvement project to assess safety of reducing pancreatic enzyme replacement therapy in children with cystic fibrosis who have restored pancreatic function as a result of CFTR modulator

P322 A quality improvement project to assess safety of reducing pancreatic enzyme replacement therapy in children with cystic fibrosis who have restored pancreatic function as a result of CFTR modulator

Plain language summary of a study looking at the long-term benefits of enzyme replacement therapy in children and teenagers with Gaucher disease type 3

What is this study about? Gaucher disease is a rare genetic condition. There are three types of Gaucher disease: type 1, type 2, and type 3 (GD3). Symptoms of GD3 include problems with the brain and spinal cord, bones, blood, enlarged liver and spleen, and slow growth. Symptoms have a great impact on the quality of life of people with GD3 and are known to cause loss of life in childhood. In Gaucher disease, people have two non-working copies of a gene called GBA, which tells the body how to make an enzyme called beta-glucosidase (which breaks down excess fats called sphingolipids). In Gaucher disease, people do not make enough beta-glucosidase enzyme, meaning sphingolipids build up inside cells, affecting many organs and systems of the body. Enzyme replacement therapy (ERT) is a treatment for Gaucher disease. Previous studies looking at ERT showed that treatment can greatly improve most symptoms and quality of life in people with Gaucher disease. How ERT may help people with GD3 is only available in small studies. What was the aim of this study? Researchers looked at long-term changes in the blood, spleen, liver, and growth in children and teenagers living with GD3 and how long they survived once they had started an ERT called imiglucerase. Researchers used data from a large global database called the International Collaborative Gaucher Group (ICGG) Gaucher Registry. The aim was to investigate if imiglucerase could improve long-term symptoms and prevent early loss of life. What were the results of this study? Low red blood cell counts (causing a condition called anaemia), low platelet (specialised blood cells that stop bleeding and bruising) counts, enlarged liver and spleen, and slow growth were the most common symptoms in people with GD3 before treatment. People with GD3 who had received imiglucerase had improved symptoms after 5 years of treatment. They also had a greater chance of living longer, with 92% of people alive after 5 years of treatment. These results show that the ERT imiglucerase helps to improve blood, spleen, liver, and growth symptoms, and most importantly that it is a life-prolonging treatment.

Experience with enzyme replacement therapy in children with late-onset Pompe disease diagnosed via newborn screening in the United States

Experience with enzyme replacement therapy in children with late-onset Pompe disease diagnosed via newborn screening in the United States

Дотримання режиму лікування і причини його порушення в дітей, хворих на муковісцидоз

Medical dietary therapy (MDT) is aimed at preventing complications related to both the chronic disease itself and complications that may develop into separate nosological forms as a result of non-compliance with such recommendations. At the same time, adherence to MDT recommendations among children is quite low, despite the adverse consequences of non-adherence to therapy. These difficulties determine the need for additional counseling by behavioral pediatricians and psychologists. Purpose - to study the degree of adherence to dietary recommendations and pancreatic enzyme replacement therapy in children with cystic fibrosis (CF) in Kyiv and the Kyiv region, and the impact on anthropometric indicators, length of hospitalization, and the probability of respiratory tract colonization by Ps. aeruginosa. Materials and methods. Interviews were conducted with 17 children with cystic CF aged 5 to 17 years, as well as their parents. Children and parents were asked to fill out the EAT-26 food attitude questionnaire. All interviewed patients were assessed for nutritional status and sputum culture. Patients were divided into 3 groups depending on the completeness of compliance with the recommendations. Results. According to the general results of the survey, only 47% of all patients are sure that they fully followed the recommendations. Children with CF who did not regularly or substandardly consume specialized food mixtures had a higher percentage of respiratory tract colonization by Ps. aeruginosa, stayed longer in the hospital, and some of them had nutritional disorders. According to the EAT-26 questionnaire and a face-to-face interview, it was established that children with CF form their attitude to eating through the prism of the perception of the diagnosis. The daily “burden of the disease” and the additional responsibilities associated with it are reflected in the patients’ answers. Conclusions. An important component of the work with children with CF is the determination of reduced adherence to diet therapy. EAT-26 testing can be useful for identifying the most significant factors that require correction in a specific child by members of a multidisciplinary team (pediatrician, nutritionist, psychologist). The research was carried out in accordance with the principles of the Declaration of Helsinki. Informed consent of the child’s parents was obtained for the research. No conflict of interests was declared by the authors.

Impact of kidney biopsy on deciding when to initiate enzyme replacement therapy in children with Fabry disease

BackgroundRecommendations on when to start enzyme replacement therapy (ERT) in children with Fabry disease (FD) differ between guidelines. In this study, kidney biopsies of a cohort of 14 untreated children and one treated child were analyzed for their morphologic changes to determine whether early initiation of ERT is indicated.MethodsAll pediatric FD patients (< 18 years old) diagnosed between 2003 and 2021 in our department who received a kidney biopsy were enrolled. Clinical symptoms; laboratory parameters regarding kidney function, such as eGFR, plasma urea, protein-creatinine, and albumin/creatinine ratio; and 14 kidney biopsies prior to ERT and one under treatment were retrospectively analyzed.ResultsA total of 14 patients were enrolled, including 9 male and 5 female children, aged 3–18 years (median age 11). Seven of the enrolled children were 10 years old or younger. Histological analysis of kidney biopsy samples revealed severe vacuolization and accumulation of inclusions in podocytes and renal tubules. The majority of cases had no FD-specific clinical or laboratory features independent of age, gender, or genotype. The youngest FD patient presenting with isolated abnormal kidney biopsy was 3 years old.ConclusionsWe demonstrate that histological lesions, typical for FD, can be observed in kidney biopsies at a very young age in patients without classical clinical symptoms or laboratory abnormalities. Thus, we recommend kidney biopsies as a possible tool for early diagnosis of renal involvement in FD. As a consequence of these early biopsy findings without a clinical correlate, an early initiation of ERT should be considered.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Home-based enzyme replacement therapy in children and adults with Pompe disease; a prospective study

BackgroundPompe disease is a lysosomal storage disease treated with life-long enzyme replacement therapy (ERT). Home-based ERT has been provided in the Netherlands since 2008 because it diminishes the burden of treatment, increases patient flexibility and autonomy, and is thus a more patient-centred approach to ERT.MethodsAll Dutch Pompe patients receiving alglucosidase alfa infusions at home were approached to participate in a questionnaire to validate the safety of home-based ERT. Prospective data on symptoms occurring during or within 48 h after infusion and retrospective data on infusion associated reactions (IARs) in the last three months were collected four times during one year.ResultsIn total, 116 out of 120 eligible patients (17 classic infantile, 2 atypical infantile, 15 childhood onset and 82 adult) filled out 423 questionnaires (response rate: 88.1%). Symptoms during or after infusion were reported 27 times in 17 patients. Fatigue was the most commonly reported health complaint (in 9.5% of patients). Four health complaints were judged to be IARs and reported to the Erasmus MC University Medical Center. None of the IARs reported in this study warranted emergency clinical care.ConclusionsOur data demonstrate that home-based ERT in Pompe disease can be safely implemented as few, mostly mild, symptoms were reported during or after infusion. Insights from this study can be used as a base for implementing home-based ERT in other countries and to further optimize patient care, as unreported mild symptoms do not pose a health risk but may still be relevant to the patient.

Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD. Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed. Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013). This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT.

Current and Future Therapeutic Approaches of Exocrine Pancreatic Insufficiency in Children with Cystic Fibrosis in the Era of Personalized Medicine.

This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1–/–) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1–/– mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.

Features of the appointment of enzyme replacement therapy in children with Cystic Fibrosis in the Russian Federation. Cross-sectional study

Relevance: Controversial issues of enzyme replacement therapy for cystic fibrosis continue to be studied, without losing relevance against the background of taking targeted drugs. Studies show that there is a large scale in the dosage of pancreatin that goes beyond the recommended values and there is no unified approach to prescribing the drug related to national and individual characteristics. Currently, there is insufficient data to substantiate consensus recommendations on enzyme therapy from the standpoint of evidence-based medicine. There is a need for scientific substantiation of the accepted therapeutic algorithm, search for optimal doses, calculation methods, correction, development of an individual approach to the appointment of pancreatin in cystic fibrosis. Objective: to study the features of pancreatin dosing in children with pancreatic insufficiency of cystic fibrosis in the Russian Federation Material and methods. 140 children (boys - 73, girls - 67) with CF aged from 1 year to 18 years (average age 8,9±5,8 years) were examined in the Department of cystic Fibrosis Scientific and Clinical Institute of Childhood of the Ministry of Health of the City of Mytishchi (clinical base of the scientific and clinical Department of cystic fibrosis). The study was conducted in 2018. The nutritional status (anthropometric indicators) of the pancreatin dose per day and for each meal was assessed using 2 calculation methods: units/kg of body weight and units/g of fat in food. Separately, these indicators were analyzed in a group of patients homozygous for the genetic variant F508del of the CFTR gene Design: cross-sectional study Results. The study showed that 67% of patients in the general group and 68% in the subgroup of patients homozygous for the genetic variant F508del of the CFTR gene received doses of pancreatin in reference values (up to 10,000 EU/kg of body weight per day). When calculating the pancreatin dose by the method per gram of fat in food, most of the patients (59%) in the general group and 47% of patients in the F508del homozygous subgroup received pancreatin doses of less than 2000 EU/g of fat, which is less than the reference values (2000-4000 EU/g). The results are consistent with the data of recent studies indicating an acceptable dosage range of pancreatin 1000-4000 EU/g of fat in food. The median daily dose of pancreatin of the subgroup with the genetic variant F508del of the CFTR gene was 1700 EU/g of fat in food, and in the general group 1500 EU/g of fat (p≥0.05), which can be attributed to the peculiarities of dosing and the need for pancreatin in the Russian pediatric population of patients with cystic fibrosis. The BMI percentile did not differ in subgroups with different doses of pancreatin when calculated by two calculation methods. The median daily dose of pancreatin in patients homozygous for the genetic variant F508del of the CFTR gene and the general group did not differ statistically. Conclusion. Most of the children in the general group and in the subgroup of homozygous F508del genetic variant received pancreatin in the range of 6000-10000 EU/kg of body weight. Most patients in the general group received less than 2000 EU/g of fat, unlike the subgroup with the F508del/F508del mutation - 2000-4000 EU/g of fat (p≥0.05). The median pancreatin of the subgroup with the F508del/F508del mutation was 1700 EU/g of fat in food, in the total group 1500 EU/g of fat (p≥0.05). High doses of pancreatin are not associated with nutritional status (BMI percentile).

The Role of Liver Function Tests in Monitoring the effect of Enzyme Replacement Therapy in Children with Gaucher Disease

Background: Gaucher disease (GD) is an autosomal recessive hereditary disease. The etiology, pathophysiology, diagnosis, and prognosis of GD in children might all be affected by a variety of biomarkers. The majority of them are linked to abnormalities caused by this lysosomal storage disorder, which is caused by a deficiency of the glucocerebrosidase enzyme that affects numerous organs including the liver, spleen, and bones. Objectives: to investigate the relevance of liver function tests in the assessment of treatment response in children with Gaucher's disease who are undergoing enzyme replacement therapy in a follow-up manner. Methods: A case-control study was performed on 67 children (girls and boys) with GD who were recruited from the Children Welfare Hospital Consultation Clinic, the Gastroenterology and Hepatology Teaching Hospital, and the Central Child's Teaching Hospital. The levels of ALT, AST, total bilirubin (TB), and total protein (TP) were assessed in the samples of 67 Gaucher children, who were classified as recently diagnosed untreated patients (n=9), patients who received ERT for 3-6 months (n=18), 6-12 months (n=20), and patients who received ERT for more than one year (n=20), and compared to twenty newly comparable age-matched controls. The practical part of the study was conducted at research laboratories in the College of Pharmacy, Al-Maaql University and the Department of Pharmacy, Al-Turath University College during the period from December 2020 to March 2021. Results: The results showed that total protein levels in patients were significantly lower than in age-matched control group. The negative significant correlations between the levels of AST, ALT, and TB with the period of receiving treatment and the positive significant correlations between the levels of total protein and the period of receiving treatment indicated that the studied parameters were significantly associated with the period of receiving ERT. The effect of ERT was also indicated by the results of the ANOVA test, which revealed significant variations in the levels of ALT, AST, total bilirubin, and total protein across the patient subgroups. Conclusions: ALT, AST, total bilirubin, and total protein have been shown to have diagnostic significance in newly diagnosed untreated children with a wide range of treatment responses, limiting their utility in treatment monitoring.

P190 Features of dosing of enzyme replacement therapy in children with cystic fibrosis in the Russian Federation: cross-sectional study

P190 Features of dosing of enzyme replacement therapy in children with cystic fibrosis in the Russian Federation: cross-sectional study

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.

Allergic Reactions at Enzyme Replacement Therapy in Children with Mucopolysaccharidosis Type II

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is rare hereditary disease caused by changes in the IDS gene and associated deficiency of lysosomal enzyme iduronate-2-sulfatase (I2S). The main treatment scheme for children with MPS II is enzyme replacement therapy (ERT) with recombinant human I2S. The major issue of ERT is development of allergic (sometimes up to severe anaphylaxis) reactions to recombinant enzymes. The article covers features of infusion-related reactions to ERT, it describes pathogenesis, diagnostic criteria management algorithm of anaphylaxis. Whereas, there is the need of further studies on allergic infusion-related reactions to ERT in children.

The role of nutrition and pancreatic enzyme replacement therapy in children with cystic fibrosis

Background Cystic fibrosis (CF) is an inherited genetic disorder with high mortality and morbidity. CF is strongly correlated with malnutrition due to higher energy losses, pancreatic insufficiency, chronic inflammation, higher resting energy expenditure, and feeding problems. Malnutrition in CF patients associated with worse survival. Thus, appropriate and prompt nutritional intervention should be addressed to reduced malnutrition in CF patients.&#x0D; Methods The literature search was performed on 9 August 2021 in four major databases such as MEDLINE, EBSCOhost, Cochrane Reviews, and Web of Sciences to find the role of nutrition and pancreatic enzyme replacement therapy in pediatrics population with cystic fibrosis.&#x0D; Recent findings In recent decades, early nutritional management and pancreatic enzyme replacement therapy (PERT) have been shown to improve CF patient’s outcomes. Nutrition should be given in higher calories compared to healthy individuals with close and regular nutritional status monitoring. High protein and fat diets are essential for CF patient’s overall survival. Adequate level of micronutrients should be ensured to avoid morbidity caused by micronutrients deficiency. Regular pancreatic insufficiency screening should be done annually in order to start PERT early. Further research focusing on body composition, growth chart, protein intake, and PERT are needed to further improve the management of CF patient.&#x0D; Conclusion Nutritional intervention and PERT play an important role in prolonging CF patient survival. Both treatments should be initiated early with nutritional status close monitoring and tailored to each individual. Collaboration with parents and children is critical to warrant that CF patients followed the dietary advice.

EP175 - One-year results of olipudase alfa enzyme replacement therapy in children with chronic visceral and neurovisceral acid sphingomyelinase deficiency

eP175 - One-year results of olipudase alfa enzyme replacement therapy in children with chronic visceral and neurovisceral acid sphingomyelinase deficiency

Development of the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement therapy (ERT) in CLN2 Disease" Based on 6 Years Treatment Experience in 48 Patients.

Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the “Hamburg Best Practice Guidelines for ICV–Enzyme Replacement Therapy (ERT) in CLN2 Disease.” Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.

Management of hypersensitivity reactions to enzyme replacement therapy in children with lysosomal storage diseases

BackgroundIntravenous recombinant enzyme replacement therapy (ERT) is currently available for 8 lysosomal diseases. Hypersensitivity reactions (HSRs) may be observed during this long-term treatment. ObjectiveTo evaluate the frequency and clinical treatment features of ERT HSRs and the management of desensitizations in children. MethodsMedical records were reviewed retrospectively for patients who received ERT. Those who had experienced HSRs to ERT were included in the study. The demographic characteristics of the patients, culprit enzyme, signs and symptoms, diagnostic tests, management of the reaction, and the protocol employed for the maintenance of ERT were recorded. ResultsDuring the study period, 54 patients received ERT in our institution. A total of 11 patients (20.4%) experienced HSR to ERT. All reactions were of immediate type. The most common symptoms were cutaneous manifestations. A total of 9 patients experienced urticaria, and 2 had anaphylaxis as initial reaction. Patients who had isolated cutaneous symptoms continued their treatments with antihistamines, corticosteroid premedication, slower infusion rate or both. Patients who had recurrent urticaria with these modalities or those who had anaphylaxis continued their ERT with desensitization (n = 8). A total of 3 patients required revisions in desensitization protocols because of recurrent anaphylaxis. ConclusionThe reactions that develop during this long-term treatment may be treated by premedication-prolonged infusion, but in some patients, desensitization protocols are necessary for the continuation of therapy. Revisions in desensitization protocols may be required.

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.