Clinical outcomes following hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis VI.

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy Syndrome) is one of approximately 50 known lysosomal storage disorders. MPS VI is characterized by an absence or deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) resulting in accumulation of dermatan sulfate. Prior to the availability of enzyme replacement therapy (ERT), the clinical management of MPS VI was limited to supportive care and allogeneic hematopoietic stem cell transplantation (HSCT); however, due to the rarity of this disease, little is known about the long-term outcomes of HSCT for MPS VI. The following retrospective study was performed using aggregate data gathered by the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1982 and 2007 to determine survival probability for patients with MPS VI following allogeneic HSCT. This analysis identified 45 MPS VI patients with a median age of 5 years (range, 1-22 years) at the time they received an allogeneic HSCT. Cumulative incidence (95% CI) of acute graft-vs.-host disease at 100 days was 36% (21-53%). Probability of survival was 78% (65-89%) at 100 days and 66% (52-79%) at 1 and 3 years. While these data are based upon small numbers of recipients, they represent the largest series to date and may help clinicians assess the relative risks and benefits of currently available therapies.

Mucopolysaccharidosis VI.

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 microg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 microg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided.

Clinical utility of endurance measures for evaluation of treatment in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

Increased functional capacity of major organ systems improves the quality of life and contributes to reductions in the morbidity associated with chronic debilitating diseases. Routine endurance tests can be used to gauge the progression of disease and the impact of therapeutic modalities in disorders with multiple organ system involvement such as with Mucopolysaccharidosis type VI (MPS VI). MPS VI is a progressive disorder affecting multiple organs and tissues due to the deficient activity of N-acetylgalactosamine-4-sulfatase leading to the accumulation of glycosaminoglycan (GAG) dermatan sulfate. Since 2005, enzyme replacement therapy (ERT) with human recombinant N-acetylgalactosamine-4-sulfatase (galsulfase) has been an available treatment option for MPS VI. These patients are routinely evaluated for extent of disability, disease progression and the impact of ERT. Evaluations are made by a combination of urinary GAG measurement and submaximal intensity endurance tests such as the 3-minute stair climb (3-MSC), and the 6- and 12-minute walk tests (6-MWT and 12-MWT). This review highlights the clinical validity of endurance measures as inexpensive diagnostic tools for diseases affecting multiple organ systems and evaluating the impact of therapeutic modalities, such as ERT for MPS VI.

Enzyme replacement therapy in the home setting for mucopolysaccharidosis VI: a survey of patient characteristics and physicians' early findings in the United States.

Galsulfase, a Food and Drug Administration-approved enzyme replacement therapy for mucopolysaccharidosis VI, is administered once weekly in a hospital setting as a 4-hour intravenous infusion. To improve convenience and alleviate family responsibilities associated with clinic visits, some physicians are transitioning appropriate patients to home infusion therapy. An online survey was conducted with 3 physicians treating 4 patients with mucopolysaccharidosis VI to better understand the factors motivating the transition to home infusion therapy, identify characteristics of appropriate candidates, and evaluate the potential impact on the lives of patients and their families. Survey results showed that home infusion may offer patients and their families increased flexibility of schedule and enhanced family life.

Reversed papilledema in an MPS VI patient with galsulfase (Naglazyme) therapy.

MPS VI (mucopolysaccharidosis VI, known as Maroteaux-Lamy syndrome) is a multi-systemic inherited disease, resulting from a deficiency of N-acetylgalactosamine-4-sulfatase, causing accumulation of the glycosaminoglycan (GAG) dermatan sulfate in all tissues. It is one of almost 50 lysosomal storage disorders. Ocular pathology is common in patients with MPS VI, with complications including ocular hypertension, progressive corneal clouding, optic nerve swelling (or papilledema) often associated with communicating hydrocephalus (Ashworth et al., Eye 20(5), 553-563, 2006; Goldberg et al., AJO 69(6), 969-975), and raised intracranial pressure (ICP) progressing to atrophy with loss of vision (Goodrich et al., Loss of vision in MPS VI is a consequence of increased intracranial pressure, 2002). This is the first case report of reversed papilledema and improved visual acuity in an 11-year-old MPS VI patient receiving galsulfase (Naglazyme), an enzyme-replacement therapy (ERT) of recombinant human arylsulfatase B (rhASB) (Harmatz et al., J Pediatr 148(4), 533-539, 2006).

Infectious disease outbreaks in competitive sports: a review of the literature.

Recent outbreaks of infectious diseases in athletes in competitive sports have stimulated considerable interest. The environments in which these athletes compete, practice, receive therapy for injuries, and travel, both domestically and internationally, provide varied opportunities for the transmission of infectious organisms. The purpose of this medical literature review is to identify the agents most commonly reported in the medical literature as responsible for infectious disease outbreaks in specific sports and their modes of transmission and to guide targeted prevention efforts. A literature review of English-language articles in medical publications that reported outbreaks of infectious diseases in competitive athletes was conducted in PubMed MEDLINE from 1966 through May 2005. Outbreaks that were solely food borne were excluded. Fifty-nine reports of infectious disease outbreaks in competitive sports were identified in the published medical literature. Herpes simplex virus infections appear to be common among wrestlers and rugby players, with no single strain responsible for the outbreaks. Methicillin-resistant Staphylococcus aureus was responsible for several recent outbreaks of soft tissue and skin infections among collegiate and professional athletes. The most common mode of transmission in outbreaks was direct, person-to-person (primarily skin-to-skin) contact. Blood-borne exposure was implicated in 2 confirmed outbreaks of hepatitis. Airborne and vector transmissions were rarely reported. This review provides an overview of infectious disease outbreaks thought to be either serious enough or unusual enough to report. Appropriate surveillance of the frequency of infections will allow sports medicine staff to identify outbreaks quickly and take necessary measures to contain further transmission and prevent future outbreaks.

Risk factors for injury in high school football players.

BACKGROUND: Many studies have reported the frequency and types of injuries in high school football players. However, few have assessed the relationship between player characteristics and risk of injury. PURPOSE: To describe the epidemiologic characteristics of and risk factors for injury in high school football players and to determine whether players' characteristics could be used to predict subsequent injury. STUDY DESIGN: Prospective cohort study. METHODS: This study was part of a 2-year prospective investigation (1998 to 1999) of risk factors for injury in 717 (343 in the 1998 season and 374 in the 1999 season) high school football players in the Oklahoma City, Oklahoma, School District. Player characteristics (playing experience, position, injury history) and physical parameters (body mass index, weight, height, grip strength) were measured at the beginning of each season. Logistic regression analysis was used to determine whether any of the baseline variables were associated with the odds of subsequent injury. RESULTS: The physical characteristics of players, such as body mass index and strength, were not associated with risk of injury. More playing experience and a history of injury in the previous season were significantly related to increased risk. Linemen were at the highest risk of injury, particularly knee injuries and season-ending injuries. CONCLUSIONS: Future research should focus on decreasing the risk of injury to linemen.

Risk factors for injury in middle school football players.

BACKGROUND: Little is known about the frequency of or risk factors for injuries in middle school or junior high school football players. PURPOSE: To examine the associations of player characteristics (injury history, conditioning, player position, special equipment) and physical parameters (body mass index, weight, height, grip strength) with risk of injury. STUDY DESIGN: Prospective cohort study. METHODS: We documented risk factors for injury in 646 middle school football players, 10 to 15 years of age, in the Oklahoma City, Oklahoma, school district during the 1998 and 1999 seasons. Player characteristics and physical parameters were measured at the beginning of both seasons. Logistic regression methods were used to determine whether baseline variables were associated with the odds of subsequent injury. RESULTS: More playing experience was the only variable significantly associated with the risk of injury in multivariate analyses. This association was observed regardless of the type of injury and even after indirectly controlling for time at risk of injury by restricting analyses to first-string players. Increasing age was significantly associated with the risk of fractures. CONCLUSIONS: Results suggest that physical characteristics play a minor role in risk of injury from football in this age group.

Acute macular neuroretinopathy: a review of the literature.

Acute macular neuroretinopathy (AMNR) is a rare condition that produces transient or permanent visual impairment. Typical cases have acute onset multifocal scotomas that correspond rather precisely with reddish, flat, or depressed circumscribed lesions in the macula. These lesions are wedge-shaped and generally point toward the fovea. The pathophysiology of AMNR is unclear, the causes are uncertain, and there is no specific treatment for this condition. This review summarizes the presentation, possible risk factors, and prognosis of the 41 cases of AMNR reported in the published, English-language literature from 1975 through April 2002. Possible areas for future research into the etiology of this rare condition are discussed.