scholarly journals Upper Limb Pathology in Children with Mucopolysaccharidoses

2021 ◽  
Vol 27 (2) ◽  
pp. 34-43
Author(s):  
V. M. Kenis ◽  
E. V. Melchenko ◽  
T. V. Markova ◽  
Ali Al Kaissi ◽  
A. V. Sapogovskiy ◽  
...  
Keyword(s):  
Upper Limb ◽  
Clinical Manifestations ◽  
Self Care ◽  
Case Series ◽  
Upper Extremities ◽  
Fine Motor ◽  
Shoulder Abduction ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Metacarpal Bones

Background. Despite the success in the treatment of children with mucopolysaccharidoses (MPS) as a result of the widespread of  enzyme  replacement  therapy  and  hematopoietic  stem  cells  transplantation,  orthopedic  manifestations  continue  to  be a  significant  problem,  while  the  pathology  of  the  upper  limbs  in  children  with  MPS  is  not  sufficiently  represented  in  the literature. The aim of this studywas to analyze orthopedic and neurological manifestations in the upper extremities of children with  mucopolysaccharidosis  based  on  a  sequential  case  series. Materials  and  Methods. We  carried  out  a  comprehensive analysis of clinical and radiological involvement of the upper extremities in 49 patients with MPS. Results. The most common complaints reated to the upper extremities were difficulties in the daily activities (dressing, self-care, playing), impairment of the fine motor skills, and muscle weakness. The most frequent clinical manifestations related to the upper extremities were limited active shoulder abduction, impaired hand grip, flexion contractures of the elbow joint, ulnar deviation of the hand. All patients with MPS types I, II, and VI had limited active and passive extension and flexion of the metacarpophalangeal and interphalangeal joints. In patients with MPS IV, hypermobility of the hand joints prevailed. We noticed minimal presence of typical clinical manifestations related to compression of the median nerve secific for carpal tunnel syndrome. The majority of patients showed a decrease in tendon and periosteal reflexes. The most pronounced decrease in muscle strength was observed in to extensors (elbow, fingers) and shoulder abductors, which may contribute to the predominant formation of a flexion pattern of contractures. On radiographs of the hand, the “melting sugar” symptom and shortening of the metacarpal bones were observed in most patients. Conclusion.Clinical and radiological manifestations related to the upper extremities take  place  in  all  types  of  the  mPS,  and  lead  to  functional  disorders  that  complicate  daily  life  and  self-care.  Upper  limb pathology in children with MPS requires earlier detection and more active treatment after comprehensive risk assessment.

scholarly journals Clinical and event-based outcomes of patients with mucopolysaccharidosis VI receiving enzyme replacement therapy in Turkey: a case series

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aslı İnci ◽  
İlyas Okur ◽  
Leyla Tümer ◽  
Gürsel Biberoğlu ◽  
Murat Öktem ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Respiratory Tract Infections ◽  
Clinical Manifestations ◽  
Case Series ◽  
Enzyme Replacement ◽  
Mps Vi ◽  
Cardiac Valve Disease ◽  
Tract Infections ◽  
Event Based

Abstract Background The objective of this study was to describe clinical manifestations and events of patients with mucopolysaccharidosis (MPS) VI in Turkey who are treated with galsulfase enzyme replacement therapy (ERT). Clinical data of 14 children with MPS VI who were followed up at the Department of Pediatrics of the Gazi University Faculty of Medicine in Ankara, Turkey were retrospectively collected from the patients’ medical records. Patients were selected based on availability of a pre-ERT baseline and follow-up clinical data for a similar period of time (1.9–3.2 years). Event data (occurrence of acute clinical events, onset of chronic events, surgeries) collected during hospital visits and telemedicine were available for up to 10 years after initiation of ERT (2.5–10 years). Results Age at initiation of ERT ranged from 2.8 to 15.8 years (mean age 7.5 years). All patients presented with reduced endurance and skeletal abnormalities (dysostosis multiplex) on radiography. Other common clinical manifestations were cardiac valve disease (N = 13), short stature (N = 11), cranial abnormalities on MRI (N = 10), spinal abnormalities on MRI (N = 7), and mild cognitive impairment (N = 6). School attendance was generally poor, and several patients had urinary incontinence. After 1.9 to 3.2 years of ERT, most patients showed improvements in endurance in the 6-min walk test and 3-min stair climb tests; the frequency of urinary incontinence decreased. ERT did not seem to prevent progression of cardiac valve disease, eye disorders, hearing loss, or bone disease. Long-term event-based data showed a high incidence of respiratory tract infections, adenotonsillectomy/adenoidectomy, reduced sleep quality, sleep apnea, and depression before initiation of ERT. The number of events tended to remain stable or decrease in all patients over 2.5–10 years follow-up. However, the nature of the events shifted over time, with a reduction in the frequency of respiratory tract infections and sleep problems and an increase in ophthalmologic events, ear tube insertions, and depression. Conclusions This case series shows the high disease burden of the MPS VI population in Turkey and provides a unique insight into their clinical journey based on real-life clinical and event-based data collected before and after initiation of ERT.

scholarly journals Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5130-5139 ◽  
Author(s):  
Ilaria Visigalli ◽  
Stefania Delai ◽  
Letterio S. Politi ◽  
Carmela Di Domenico ◽  
Federica Cerri ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Manifestations ◽  
Cardiac Insufficiency ◽  
Type I ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I ◽  
Hsc Transplantation

AbstractType I mucopolysaccharidosis (MPS I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase, which results in glycosaminoglycan accumulation in tissues. Clinical manifestations include skeletal dysplasia, joint stiffness, visual and auditory defects, cardiac insufficiency, hepatosplenomegaly, and mental retardation (the last being present exclusively in the severe Hurler variant). The available treatments, enzyme-replacement therapy and hematopoietic stem cell (HSC) transplantation, can ameliorate most disease manifestations, but their outcome on skeletal and brain disease could be further improved. We demonstrate here that HSC gene therapy, based on lentiviral vectors, completely corrects disease manifestations in the mouse model. Of note, the therapeutic benefit provided by gene therapy on critical MPS I manifestations, such as neurologic and skeletal disease, greatly exceeds that exerted by HSC transplantation, the standard of care treatment for Hurler patients. Interestingly, therapeutic efficacy of HSC gene therapy is strictly dependent on the achievement of supranormal enzyme activity in the hematopoietic system of transplanted mice, which allows enzyme delivery to the brain and skeleton for disease correction. Overall, our data provide evidence of an efficacious treatment for MPS I Hurler patients, warranting future development toward clinical testing.

scholarly journals Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 189
Author(s):  
Christiane S. Hampe ◽  
Jacob Wesley ◽  
Troy C. Lund ◽  
Paul J. Orchard ◽  
Lynda E. Polgreen ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Common Disease ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Hurler Syndrome ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Disease ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.

scholarly journals The impact of contemporary treatments on the perioperative care of children with mucopolysaccharidoses: A case series and review of the literature.

2019 ◽  
Author(s):  
Grant Stuart ◽  
Carolyne Pehora ◽  
Gail Wong
Keyword(s):  
Difficult Airway ◽  
Perioperative Care ◽  
Case Series ◽  
Anesthetic Techniques ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Operative Care ◽  
Difficult Airways ◽  
The Impact ◽  
Mps I

Abstract Background: Patients with mucopolysaccharidosis (MPS) present significant perioperative challenges. We aimed to document the perioperative care of children with MPS undergoing anesthesia and to describe the impact of hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT) on the anesthetic management of these patients. Methods: We performed a retrospective chart review of patients with MPS anesthetised for surgical or investigative procedures at the Hospital for Sick Children in Toronto between January 2000 and December 2014. Data on MPS treatment, co-morbidities, anesthetic techniques, airway management, post-operative care and perioperative complications were collected. Results: 66 children with MPS underwent 332 anesthetics for 345 procedures. The overall rate of difficult airway was 42%. Of 29 patients with MPS I (Hurler syndrome), 66% were treated with HSCT and 34% with ERT. In those treated with HSCT, 19% had difficult airways, compared with 67% in patients who received neither treatment. 90% of patients with MPS II (Hunter syndrome) had difficult airways. ERT did not improve airway difficulty in MPS I or II patients. 32% of all anesthetics were conducted without airway instrumentation. Direct laryngoscopy, was used in 26% of all anesthetics, the laryngeal mask airway in 26%, fibreoptic bronchoscope in 7%, and video laryngoscope in 5%.Conclusions: Patients with MPS I who have had HSCT are less likely to have a difficult airway compared with those not treated with HSCT. ERT in MPS I and II patients did not alter the incidence of difficult airway. A third of MPS patients underwent anesthesia for diagnostic imaging or minor interventional radiology procedures without airway instrumentation.

scholarly journals Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jane E. Potter ◽  
Gemma Petts ◽  
Arunabha Ghosh ◽  
Fiona J. White ◽  
Jane L. Kinsella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Multimodal Therapy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Venous Access ◽  
Cell Transplant ◽  
New Paradigm ◽  
Hematopoietic Stem ◽  
Wolman Disease ◽  
Enzyme Replacement

Abstract Background Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. Results We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT—multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition. Conclusion We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.

The case for skin camouflage in the management of upper limb scarring – A case series

Hand Therapy ◽  
2021 ◽  
pp. 175899832110078
Author(s):  
Laura Adamson ◽  
Anna Selby
Keyword(s):  
Upper Limb ◽  
Case Series ◽  
Primary Objective ◽  
Self Confidence ◽  
Published Evidence ◽  
Case Series Study ◽  
Visual Impact ◽  
Series Study ◽  
Increasing Function

Introduction For some people the appearance of their hands is as important as function. Upper limb scarring can cause some patients distress. Skin camouflage is an intervention that can be used to reduce the visual impact of a scar but there is limited published evidence for its use for hand scarring. Methods This is a case series study with a primary objective to determine whether skin camouflage reduces distress in patients with an upper limb scar and to evaluate this new service. Patients experiencing distress from an upper limb scar were recruited from a hand therapy outpatient clinic. The intervention delivered was a one hour skin camouflage session. Photographs of the upper limb pre and post skin camouflage intervention were taken. The patient-rated Michigan Hand Questionnaire (MHQ) and Derriford Appearance Scale (DAS24) were completed before treatment, at 1 week and 1 month after treatment. Results Six participants reporting distress from an upper limb scar received skin camouflage intervention. Only three out of six participants completed all follow-up. All three showed improvement in at least two domains of the MHQ (function and aesthetics) at one month post treatment. Increased confidence during functional and work-based activities was also reported on the DAS24. Participants reported increased engagement in daily activities as a result of being able to camouflage their scars. Conclusions This small case series shows that skin camouflage intervention may be beneficial for some patients who are experiencing distress related to an upper limb scar by increasing function and self-confidence.

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

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sebile Kılavuz ◽  
Sibel Basaran ◽  
Deniz Kor ◽  
Fatma Derya Bulut ◽  
Sevcan Erdem ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Clinical Data ◽  
Treatment Initiation ◽  
Case Series ◽  
Enzyme Replacement ◽  
Morquio A ◽  
Over Time ◽  
Morquio A Syndrome

Abstract Background This 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). Results At 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. Conclusions Overall, 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.

scholarly journals A Novel Retensioning Technique for Arthroscopic Repair of PASTA Lesions: A Clinical and Radiologic Outcome Study of 24 Shoulders

2021 ◽  
Vol 9 (3) ◽  
pp. 232596712098688
Author(s):  
Su Cheol Kim ◽  
Jong Ho Jung ◽  
Sang Min Lee ◽  
Jae Chul Yoo
Keyword(s):  
Constant Score ◽  
Case Series ◽  
Tendon Healing ◽  
Shoulder Abduction ◽  
Level Of Evidence ◽  
Simple Shoulder Test ◽  
Shoulder Range Of Motion ◽  
Functional Scores ◽  
The Mean

Background: There is no consensus on the ideal treatment for partial articular supraspinatus tendon avulsion (PASTA) lesions without tendon damage. Purpose: To introduce a novel “retensioning technique” for arthroscopic PASTA repair and to assess the clinical and radiologic outcomes of this technique. Study Design: Case series; Level of evidence, 4. Methods: A retrospective analysis was performed on 24 patients whose PASTA lesion was treated using the retensioning technique between January 2011 and December 2015. The mean ± SD patient age was 57.6 ± 7.0 years (range, 43-71 years), and the mean follow-up period was 57.6 ± 23.4 months (range, 24.0-93.7 months). Sutures were placed at the edge of the PASTA lesion, tensioned, and fixed to lateral-row anchors. After surgery, shoulder range of motion (ROM) and functional scores (visual analog scale [VAS] for pain, VAS for function, American Shoulder and Elbow Surgeons [ASES] score, Constant score, Simple Shoulder Test, and Korean Shoulder Score) were evaluated at regular outpatient visits; at 6 months postoperatively, repair integrity was evaluated using magnetic resonance imaging (MRI). Results: At 12 months postoperatively, all ROM variables were improved compared with preoperative values, and shoulder abduction was improved significantly (136.00° vs 107.08°; P = .009). At final follow-up (>24 months), the VAS pain, VAS function, and ASES scores improved, from 6.39, 4.26, and 40.09 to 1.00, 8.26, and 85.96, respectively (all P < .001). At 6 months postoperatively, 21 of the 24 patients (87.5%) underwent follow-up MRI; the postoperative repair integrity was Sugaya type 1 or 2 for all of these patients, and 13 patients showed complete improvement of the lesion compared with preoperatively. Conclusion: The retensioning technique showed improved ROM and pain and functional scores as well as good tendon healing on MRI scans at 6-month follow-up in the majority of patients. Thus, the retensioning technique appears to be reliable procedure for the PASTA lesion.

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