Pregnancy in patients with mucopolysaccharidosis: a case series.

The mucopolysaccharidoses (MPS disorders) are rare inherited diseases associated with multi-organ accumulation of glycosaminoglycans, leading to musculoskeletal, respiratory, cardiac, neurological, ophthalmological, otolaryngological, and gastrointestinal abnormalities. As a result of improvements in diagnosis, multi-disciplinary care, and therapies such as enzyme replacement therapy and hematopoietic stem cell transplantation, an increasing number of patients with MPS are reaching adulthood and are involved in family planning. Data on fertility and pregnancy outcome in MPS is sparse and comprises primarily isolated case reports. To address this evidence gap, we present a case series on fertility and pregnancy in eight mothers and five fathers with MPS. This case series demonstrates that women with MPS have high-risk pregnancies and deliveries secondary to their underlying disease. However, with appropriate pre-conceptual multi-disciplinary evaluation, optimization and discussion regarding potential risks, combined with regular multi-disciplinary maternal and fetal surveillance in a tertiary center, the outcome of most pregnancies in this case series seems to be favorable with all babies developing normally. Partners of fathers with MPS had uncomplicated pregnancies and deliveries. All children were healthy, with normal growth and development.

Does Strict Adherence to the Ponseti Method Improve Isolated Clubfoot Treatment Outcomes? A Two-institution Review.

BACKGROUND: Despite being recognized as the gold standard in isolated clubfoot treatment, the Ponseti casting method has yielded variable results. Few studies have directly compared common predictors of treatment failure between institutions with high versus low failure rates. QUESTIONS/PURPOSES: We asked: (1) is the provider's rigid adherence to the Ponseti method associated with a lower likelihood of unplanned clubfoot surgery, and (2) at the institution that did not adhere rigidly to Ponseti's principles, are any demographic or treatment-related factors associated with increased likelihood of unplanned clubfoot surgery? METHODS: After institutional review board approval, a consecutive series of patients with a diagnosis of isolated clubfoot who underwent treatment between January 2003 and December 2007 were identified. At Institution 1, 91 of 133 patients met the eligibility criteria and were followed for a minimum of 2 years compared with 58 of 58 patients at Institution 2. At Institution 1, 16 providers managed care using a conservative casting approach based on the Ponseti method. However, treatment was adapted by the provider(s). At Institution 2, one orthopaedic surgeon managed care with strict adherence to the Ponseti method. Surgical indications at both institutions included the presence of a persistent equinovarus foot position while standing. A chart review was used to collect data related to proportion of patients undergoing unplanned additional treatment for deformity recurrences after Ponseti casting, demographics, and treatment patterns. RESULTS: The proportion of subjects who underwent unplanned major surgical intervention was greater (odds ratio [OR], 51.1; 95% CI, 6.8-384.0; p < 0.001) at Institution 1 (60 of 131, 47%) compared with Institution 2 (two of 91, 2%). There was no difference (p = 0.200) in the proportion of patients who underwent additional casting, repeat tendo Achilles lengthening, and/or anterior tibialis tendon transfer only (minor recurrence) at Institution 1 (nine of 131, 7%) compared with Institution 2 (11 of 91, 13%). At Institution 1, an increase in the number of revision casts (multiple vs no casts, hazard ratio [HR] = 3.9; 95% CI, 2.0-7.6; p < 0.001) and an increase in the number of cast-related complications (multiple vs no complications, HR = 2.8; 95% CI, 1.2-6.7; p = 0.019) were associated with increased risk of major surgery in the multivariate analysis. CONCLUSIONS: Rigid commitment to the Ponseti method in the conservative treatment of patients with isolated clubfoot was associated with a lower risk of subsequent unplanned surgical intervention. In addition, clubfoot treatment programs that use a care model that prioritizes continuity in care and dedication to the Ponseti method may decrease the proportion of patients who undergo unplanned surgical intervention. LEVEL OF EVIDENCE: Level III, therapeutic study.

Expert Opinions on Managing Fertility and Pregnancy in Patients With Mucopolysaccharidosis

Abstract The mucopolysaccharidosis (MPS) disorders are rare genetic diseases caused by deficiencies in lysosomal enzymes involved in the degradation of glycosaminoglycans, leading to pulmonary, cardiac and neurological dysfunctions, skeletal anomalies, impaired vision, and/or hearing and shortened life spans. Whereas in the past, few individuals with MPS reached adulthood, better diagnosis, multidisciplinary care, and new therapies have led to an increasing number of adult patients with MPS. Therefore, fertility and pregnancy questions in this patient population are becoming more important. Management of fertility issues and pregnancy in patients with MPS is challenging due to the lack of documented cases and a dearth in the literature on this topic. This review presents multidisciplinary expert opinions on managing fertility and pregnancy based on case studies and clinical experience presented at a meeting of MPS specialists held in Berlin, Germany, in April 2015. An overview of the existing literature on this subject is also included.

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome).

BACKGROUND: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure. OBJECTIVE: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease. METHODS: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme(®), BioMarin Pharmaceutical Inc.), treatment naïve patients (n = 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients ≤25 years of age with 513 height measurements were used for constructing reference growth curves. RESULTS: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or ≤200 µg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) µg/mg creatinine for the patients ≤25 years of age with rapidly (n = 131) and slowly (n = 76) progressing MPS VI disease, respectively. The median growth curves for patients with ≤ and >200 µg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population. CONCLUSION: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients.

A comparative study of two types of urinary sheath.

AIM: The aim of this study was to compare the newly developed Conveen Optima urinary sheath with the established Clear Advantage urinary sheath in terms of patient satisfaction and preference. METHOD: This was a randomised, prospective, open, crossover study, in which each participant tested 10 urinary sheaths. RESULTS: Conveen Optima provided a higher feeling of security, was easier to handle and apply and was more comfortable to wear than Clear Advantage. Furthermore, Conveen Optima was easier to apply with gloves. Finally, the overall product preference for the Conveen Optima sheath was 67 per cent. CONCLUSION: The new Conveen Optima urinary sheath was found to perform better than the well-established Clear Advantage sheath. Declaration of interest This study was funded by Coloplast A/S.

Phase I trial of an all-oral combination chemotherapy regimen: topotecan and capecitabine in solid tumor patients.

The objective of this phase I study was to investigate the safety of an all-oral combination chemotherapy regimen: topotecan and capecitabine. Topotecan was administered once a day for 5 consecutive days followed by 2 days of rest and was administered again for 5 consecutive days. The starting dose of topotecan was 0.5 mg/m2/d(-1). Capecitabine was administered concurrently at an oral dose of 1800 mg/m2/d(-1) divided twice daily for 14 concurrent consecutive days. Each cycle of treatment was 21 days. Topotecan pharmacokinetic studies were performed on day 1 of cycles 1 and 2. Nineteen patients with refractory cancer were treated. Dose-limiting toxicity (thrombocytopenia, diarrhea) was observed in 2 of 3 patients at a topotecan dose of 2.0 mg/m2/d(-1). A total of 10 patients were treated at the maximum-tolerated dose of topotecan (1.5 mg/m2/d(-1)) and only 1 treatment-related grade 3 nonhematologic toxic event was demonstrated; however, grade 3 hematologic toxicity was observed in 8 of 10 patients at the maximum-tolerated dose, although no correlated clinical sequela resulted. One patient achieved a partial response and 7 achieved stable disease for 4 months or longer. Measurement of plasma topotecan showed pharmacokinetics consistent with no alteration by capecitabine. In conclusion, we recommend further investigation of oral topotecan (1.5 mg/m2/d(-1)) on days 1 to 5 of each week for 2 weeks in combination with capecitabine (180 mg/m2 twice daily) on days 1 to 14 within a 21-day cycle.