Tracheostomy in mucopolysaccharidosis type II (Hunter's Syndrome).

OBJECTIVE: Patients with mucopolysaccharidosis type II (MPS II) may develop progressive multi-level upper airway obstruction. Despite the unique challenges presented by these complex patients, tracheostomy remains an important intervention to safeguard the airway when other interventions have failed or when the airway obstruction involves multiple sites. Airway involvement is largely responsible for the significant anaesthetic risk seen in MPS II. We reviewed our tertiary unit's experience of tracheostomies in patients with MPS II. STUDY DESIGN: Retrospective study. METHODS: Case note review of MPS II patients requiring tracheostomy at our tertiary institution. The primary outcome measure used for this study was complications following tracheostomy. RESULTS: We identified 10 MPS II patients requiring tracheostomy to manage upper airway obstruction. Mean age at which tracheostomy was 11 years 2 months (range 4 years 6 months to 28 years 10 months). Tracheostomy insertion was indicated in 3 scenarios: (1) to safeguard an anticipated difficult airway prior to a planned non-ENT surgical procedure, (2) to treat refractory progressive upper airway obstruction and (3) emergency airway management. Complications recorded included infratip and suprastomal granulations, local wound infection and skin ulceration from mechanical trauma. There were no immediate postoperative complications. CONCLUSIONS: Progressive upper airway obstruction is common in children with MPS II. Tracheostomy is an effective way of managing airway obstruction when less invasive interventions are no longer adequate. Tracheostomy in these patients can be technically difficult and although the complications of tracheostomy in MPS II do not significantly differ from other patient groups, the implications and management complexity vary considerably. The impact of ERT on airway obstruction is not yet fully understood, with tracheostomies likely to remain an important airway adjunct in some patients who fail to respond to ERT, or in those patients surviving into adulthood. It is vital that a multidisciplinary team, comprising clinicians with experience in managing such patients, are involved in airway management of patients with MPS II to enable the best standard of care to be given. The significant additional implications of a tracheostomy in a patient with MPS II, in terms of safety, aftercare and potentially life-threatening complications must be discussed in detail with the patient's family and/or carers. LEVEL OF EVIDENCE: 2c.

Mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses (MPS) and mucolipidoses (ML) are progressive storage disorders that share many clinical features varying from facial dysmorphism, bone dysplasia, hepatosplenomegaly, neurological abnormalities, developmental regression, and a reduced life expectancy at the severe end of the clinical spectrum to an almost normal clinical phenotype and life span in patients with more attenuated disease. MPS and ML are transmitted in an autosomal recessive manner, except for the X-linked MPS II (Hunter syndrome). Diagnosis is initially by detecting partially degraded GAG or oligosaccharide in urine and confirmed by specific enzyme assays in serum, leukocytes, or skin fibroblasts. For the majority of disorders treatment is palliative, but there have been important advances in the use of specific enzyme replacement therapy strategies for some MPS disorders and this is an area of very rapid development. In addition, hematopoietic stem cell transplantation (HSCT) can improve outcome in carefully selected patients with MPS (especially MPS IH, Hurler syndrome), but this procedure is associated with significant risk. Gene augmentation/transfer using a variety of vectors has been successful in animal models but has not yet been successfully performed in a human patient with one of these disorders. It is important to remember that prenatal diagnosis is possible for all of these disorders.

Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of four enzymes involved in the catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative disorder, with a progressive decline in children's intellectual and physical functioning. There is currently no cure for the disorder. To date there is a paucity of research on how this disorder impacts parents psychological functioning. Specifically, research in the area has failed to employ adequate control groups to assess if the impact of this disorder on parents psychological functioning differs from parenting a child with intellectual disability (ID). The current study examined child behaviour and parental psychological functioning in 23 parents of children with MPS III and 23 parents of children with ID. Parents completed postal questionnaires about their child's behaviour and abilities and their own psychological functioning. Parents of children with MPS III reported fewer behavioural difficulties as their child aged, more severe level of intellectual disability, and similar levels of perceived social support, coping techniques, stress, anxiety and depression levels as parents of children with ID. Both groups of parents scored above the clinical cut off for anxiety and depression. Parents of children with MPS III rated themselves as significantly less future-orientated and goal directed than parents of children with ID. Services should develop support packages for parents of children with MPS III that incorporate an understanding of the unique stressors and current-difficulty approach of this population. Future research should examine gender differences between parental psychological functioning, using mixed qualitative and quantitative approaches, and utilise matched developmental level and typically developing control groups.

Orthopedic manifestations in patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in the Hunter Outcome Survey.

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare, inherited disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. As a result of this deficiency, glycosaminoglycans accumulate in lysosomes in many tissues, leading to progressive multisystemic disease. The cardiopulmonary and neurological problems associated with MPS II have received considerable attention. Orthopedic manifestations are common but not as well characterized. This study aimed to characterize the prevalence and severity of orthopedic manifestations of MPS II and to determine the relationship of these signs and symptoms with cardiovascular, pulmonary and central nervous system involvement.Orthopedic manifestations of MPS II were studied using cross-sectional data from the Hunter Outcome Survey (HOS). The HOS is a global, physician-led, multicenter observational database that collects information on the natural history of MPS II and the long-term safety and effectiveness of enzyme replacement therapy.As of January 2009, the HOS contained baseline data on joint range of motion in 124 males with MPS II. In total, 79% of patients had skeletal manifestations (median onset, 3.5 years) and 25% had abnormal gait (median onset, 5.4 years). Joint range of motion was restricted for all joints assessed (elbow, shoulder, hip, knee and ankle). Extension was the most severely affected movement: the exception to this was the shoulder. Surgery for orthopedic problems was rare. The presence of orthopedic manifestations was associated with the presence of central nervous system and pulmonary involvement, but not so clearly with cardiovascular involvement.Orthopedic interventions should be considered on an individual-patient basis. Although some orthopedic manifestations associated with MPS II may be managed routinely, a good knowledge of other concurrent organ system involvement is essential. A multidisciplinary approach is required.

Enzyme replacement therapy with imiglucerase in a Taiwanese child with type 1 Gaucher disease.

The treatment of type 1 Gaucher disease has dramatically improved with the development of enzyme replacement therapy (ERT). To date, however, imiglucerase treatment of this disease in Taiwanese pediatric patients has not been reported. A Taiwanese child with type 1 Gaucher disease was regularly treated with imiglucerase beginning October 1998. This 12-year 10-month-old boy had undergone splenectomy when he was 4 years old. He received intravenous imiglucerase 60 U/kg every 2 weeks for 78 months. No signs of pubertal development were documented at the commencement of ERT. There were no serious adverse effects. The patient had significant improvement in skeletal deformity, a dramatic decrease in liver size, markedly increased linear growth, alleviation of bone pain and bone crises, correction of anemia, and improved bone mineral density. ERT with imiglucerase improved the quality of life in this child with type 1 Gaucher disease.