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Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome.

ABSTRACT: BACKGROUND:It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood-brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT. METHODS:In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children's clinical characteristics, their siblings' cognitive development, and their parents' educational levels. RESULTS:The patients' intelligence scores ranged from normal to mentally delayed (range test scores 52-131). In 90%, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings' test scores (median for patients?=?104, median for siblings?=?88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms. CONCLUSION:Our study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully.

SUBMITTER: Ebbink BJ

PROVIDER: S-EPMC4754322 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome.

Ebbink Berendine J BJ Brands Marion M G MM van den Hout Johanna M P JM Lequin Maarten H MH Coebergh van den Braak Robert R J RR van de Weitgraven Rianne L RL Plug Iris I Aarsen Femke K FK van der Ploeg Ans T AT

Journal of inherited metabolic disease 20151008 2

<h4>Background</h4>It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood-brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT.<h4>Methods</h4>In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning a ...[more]

PMID: 26450354

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Project description:BackgroundResearch about pediatric patients' perspective on mucopolysaccharidosis type VI (MPS VI) and its impact on daily life is limited. We aimed to identify the disease concepts of interest that most impact function and day-to-day life of pediatric patients with MPS VI, and to consider clinical outcome assessments (COAs) that may potentially measure meaningful improvements in these concepts.MethodsPotential focus group participants were identified by the National MPS Society (USA) and invited to participate if they self-reported a clinician-provided diagnosis of MPS VI and were 4 to 18 years, receiving enzyme replacement therapy (ERT), and available to attend a 1-day focus group with their caregiver in Dallas, TX, USA. The focus group consisted of a series of polling and open-ended concept elicitation questions and a cognitive debriefing session. The discussion was audio recorded, transcribed verbatim, and analyzed to identify disease concepts of interest and functional impacts most relevant to participants.ResultsOverall, caregivers (n = 9) and patients with MPS VI (n = 9) endorsed that although their children/they receive ERT, residual symptoms exist and impact health-related quality of life. The key disease concepts of interest identified were impaired mobility, upper extremity and fine motor deficits, pain, and fatigue. Pain was unanimously reported by all patients across many areas of the body and impacted daily activity. Key disease concepts were mapped to a selection of pediatric COAs including generic measures such as PROMIS®, PODCI, CHAQ, and PedsQL™. Caregivers endorsed the relevance of PODCI and PROMIS Upper Extremity, Mobility, and Pain items and all patients completed the NIH Toolbox Pegboard Dexterity Test. Additional COAs that aligned with the disease concepts included range of motion, the 2- and 6-min walk tests, timed stair climbs, Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition, grip strength, pain visual analog scale, and the Faces Pain Scale-Revised.ConclusionAn MPS VI focus group of pediatric patients and their caregivers identified impaired mobility, upper extremity and fine motor deficits, pain, and fatigue as key disease concepts of interest. These disease concepts were mapped to existing pediatric COAs, which were provided to the group for endorsement of their relevance.

Project description:A long-term follow-up was made of 12 elbows operated upon between 1971 and 1986, with more than 20 years' follow-up, in nine males and three females, age at the time of surgery between 10 and 19 years . Eight right and four left elbows were involved, and there were three aetiological causes. Seven cases were sequelae of elbow fractures, of which five were supracondylar and two were of the olecranon. There were four cases of juvenile rheumatoid arthritis and one was post-osteomyelitis. The surgical technique involved a modification made by Vainio of MacAusland's technique (wider resection of the osseous ends and total covering of the bloody surfaces) [5, 9]. After extirpating the tissue blocking the joint, we proceeded to remodel the distal humerus in a wide V shape, the proximal end of the ulnar and, if necessary, the radial head. The proximal end of the ulna was sectioned transversely. All surgery was carried out sub-periosteally. Then, an interposition material was placed in one piece and sutured over the distal humerus and cut ends of the ulna and radius. The articular ends were brought together, and the capsule was closed using equidistant stitching, as is the skin. A small compression bandage was applied, and the arm was immobilised with a collar and cuff sling, with the forearm flexed to slightly less than a right angle. In ten cases, the interposition material was fascia lata grafts; in one case, skin graft and in one case, Gelfoam graft. Early rehabilitation began when post-operative pain allowed. Follow-up ranged from 25 to 32 years. Pre-surgical movement ranged between 90 degrees and 120 degrees of flexion and 30 degrees and 90 degrees of extension. Post-operative range varied between 90 degrees and 150 degrees of flexion. The five cases of full pre-operative ankylosis achieved between 90 degrees and 150 degrees of flexion and between 0 degrees and 70 degrees of extension. The total range of motion at the latest follow-up varied from 35 degrees to 150 degrees . Patients who were able to perform flexion of 120 degrees or more were considered to be excellent, those between 90 degrees and 119 degrees were graded good, from 60 degrees to 89 degrees fair and those 59 degrees or less poor. The ability to attain a hand to mouth position requires a mobility of 120 degrees . We obtained excellent results in two patients, good results in three, fair results in four and poor results in three. The fascia lata was used in 83% of cases, obtaining excellent to good results in five patients (41%). Elbow interposition arthroplasty has its indications in children and adolescents where arthrodesis or total joint replacement cannot be performed.

Project description:IntroductionThe classic ketogenic diet (cKD) is an isocaloric, high fat, low-carbohydrate diet that induces the production of ketone bodies. High consumption of dietary fatty acids, particularly long-chain saturated fatty acids, could impair nutritional status and increase cardiovascular risk. The purpose of this study was to evaluate the long-term effects of a 5-year cKD on body composition, resting energy expenditure, and biochemical parameters in children affected by Glucose Transporter 1 Deficiency Syndrome (GLUT1DS).MethodsThis was a prospective, multicenter, 5-year longitudinal study of children with GLUT1DS treated with a cKD. The primary outcome was to assess the change in nutritional status compared with pre-intervention, considering anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters such as glucose and lipid profiles, liver enzymes, uric acid, creatinine, and ketonemia. Assessments were conducted at pre-intervention and every 12 months of cKD interventions.ResultsKetone bodies increased significantly in children and adolescents, and remained stable at 5 years, depending on the diet. No significant differences were reported in anthropometric and body composition standards, as well as in resting energy expenditure and biochemical parameters. Bone mineral density increased significantly over time according to increasing age. Body fat percentage significantly and gradually decreased in line with the increase in body weight and the consequent growth in lean mass. As expected, we observed a negative trend in respiratory quotient, while fasting insulin and insulin resistance were found to decrease significantly after cKD initiation.ConclusionLong-term adherence to cKD showed a good safety profile on anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters, and we found no evidence of potential adverse effects on the nutritional status of children and adolescents.

Dataset Information

Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome.

Publications

Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome.

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