Monitoring and management
Once Hunter syndrome has been diagnosed, it is valuable to carefully monitor the extent and development of the symptoms, because of the progressive nature of the disease. 1
Monitoring is best performed by a multidisciplinary team of specialists, each focusing on their own area of expertise, but working together to create an overall assessment of the patient. 1
It may be helpful for one healthcare professional to take on the overarching support role of care coordinator to ensure the patient is receiving all the attention needed. The role of care coordinator may fall on the patient’s primary care physician or the specialist with most experience of MPS II. The majority of MPS II patients are children, but some patients are adults, therefore both paediatricians and adult primary care physicians may be involved in coordinating care (see below for more information about the multidisciplinary team involved in MPS II care and transitioning from paediatric to adult care).
It is good practice that each organ affected by Hunter syndrome is evaluated carefully and at regular intervals, to discover any decline in function that requires clinical intervention. Monitoring is best performed by a multidisciplinary team of specialists, each focusing on their own area of expertise, but working together to create an overall assessment of the patient. 1
The following information about monitoring and managing Hunter syndrome patients is based on published research, and is not intended to be an exhaustive guideline. If in doubt, please consult a qualified medical professional. 1
Physical examinations (every 6 months)
A basic physical examination should be conducted regularly on all patients, checking quantitative features such as height, weight, head circumference, blood pressure, joint stiffness and abdominal size, but also assessing pain and quality of life. This will be the first opportunity to discover clinical problems that should be further investigated. 2
Urinary GAG levels (every 6 months)
Urine samples should be collected regularly to measure the amount of GAG excretion in patients; this assessment may help to indicate the system-wide progress of the disease, and encourage more detailed physical assessment. 2
6-minute walk test (every 6 months)
The 6-minute walk test (6MWT) is a simple practical test, conducted by measuring the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. This test assesses the global and integrated response of multiple affected systems (e.g. the pulmonary and cardiovascular systems, systemic and peripheral circulation, and muscle nerves and strength). Most importantly, Hunter syndrome patients with progressive neurodegeneration will particularly struggle to maintain their performance over time. Though, this test does not interrogate any specific system, it can be used to monitor decline. 2
Hearing tests (every 6–12 months)
Hearing issues in Hunter syndrome patients can contribute to behavioural problems and learning difficulties in addition to requiring surgeries, so it is important to perform regular otological and audiological evaluations of patients. 1,2
Eye examinations (every year)
Eye tests should be carried out on Hunter syndrome patients including a vision exam to test for eyesight loss, electroretinography to determine retinal dysfunction and ophthalmoscopy to assess any pigment change or loss of field of vision. 1,2
Examinations to monitor bone and joint complications (in response to symptoms)
Joint stiffness can be initially judged by a physical examination but advanced monitoring may involve radiography of the spine and hip to check for arthropathies and spinal instability. 1,2
ECG and heart ultrasound (every 1–3 Years)
Cardiac problems are common in Hunter syndrome and can be monitored using echocardiography, 12-lead electrocardiography and Holter monitoring. 1,2
Lung function (every year)
Lung function is affected by airway obstruction, mucosal thickening, diaphragmatic muscle strength and rib deformities. Given that respiratory issues are a common cause of death, it is vital to measure lung function in Hunter syndrome patients. 1,4
Behavioural/cognitive assessments (age-appropriate/annual)
Behavioural and cognitive assessments should be combined with assessments of the auditory and respiratory systems, as non-neuronopathic symptoms of Hunter syndrome may contribute to the cognitive dysfunction of patients. Regular neurobehavioural assessments can be performed by specialist behavioural therapists to inform appropriate management. 2
A 2017 consensus paper gives recommendations for the methodology for cognitive and adaptive assessments, for example, which instrument is the most appropriate for each age group, standardising testing protocols to aid comparability, and using assessors with experience of the disease. In this way, change in cognitive ability can be more accurately tracked and understood. 3
Other neurological monitoring (age-appropriate/annual)
In the later stages of Hunter syndrome, advanced neurological symptoms such as spinal cord compression, communicating hydrocephalus and seizures may manifest. Physicians conducting basic physical examinations who notice symptoms of these underlying advanced features may refer the patient onwards for multidisciplinary and specialist management, including MRI, cervical spine flexion/extension and hand function tests. 2
Management of the disease demands that the physician be aware of the special issues surrounding the patient with Hunter syndrome and that a multidisciplinary approach should be taken
- Dr David Whiteman
Hunter syndrome is best managed with a multidisciplinary team (MDT) comprised of a number of specialists, including: 1
There are inherent risks in intubating and extubating a patient with Hunter syndrome under general anaesthesia, as the anatomical deformities complicate the procedure. It is best that the anaesthetist assesses the patient before, during and after surgery, to manage intubation difficulties or postprocedural oedemas. 1
Learn more about the management of Hunter syndrome patients by anaesthetists in Information for anaesthetists.
Cardiac valve disease is highly prevalent amongst Hunter syndrome patients, so it is good practice to regularly monitor cardiac disease progression. Assessments should also be made before any surgeries. 2
Learn more about the management of Hunter syndrome patients by cardiologists in Information for cardiologists.
An ENT specialist may be the first physician to recognise Hunter syndrome in a patient, and they have an important role in the multidisciplinary management of patients. Otological and audiological evaluations carried out annually can be used to manage the expectations of the family and other physicians of the patient’s responses, and respiratory involvement due to airway obstructions can be assessed to prepare for surgeries. 1
Learn more about the management of Hunter syndrome patients by ENT specialists in Information for ENTs.
The gastroenterologist is important in Hunter syndrome management to support with clinical issues relating to an enlarged liver (hepatomegaly) and spleen (splenomegaly), or abdominal hernias. Later in the disease, these specialists may also provide care to deal with bladder obstructions, and chronic constipation, diarrhoea and bladder dysfunction. 1 Recurrent watery diarrhoea is one of the ‘red flag’ signs of Hunter syndrome that occurs early in the disease course. 5
Geneticist and genetic counsellor
The geneticist and genetic counsellor can inform other specialists of the genotype of the mutation (although this is not necessarily related to prognosis) and educate the family on the need to screen other individuals for Hunter syndrome mutations, and the probability of finding undiagnosed Hunter syndrome children and carriers. 2
The neurologist will perform assessments on, and provide management for, Hunter syndrome patients with neuronopathic involvement, such as behavioural problems, cognitive impairment, or more advanced neuronopathic symptoms. Later in the disease, the neurologist is essential as further deterioration occurs and they collaborate with other specialists to manage multisystemic neuronopathic symptoms. 2
Learn more about the management of Hunter syndrome patients by neurologists in Information for neurologists.
Orthopaedic surgeons can perform surgeries such as decompression of the spinal cord or median nerve, instrumented fusion (to stabilise and strengthen the spine), arthroscopy, hip or knee replacement, and correction of the lower limb axis, in order to help preserve long-term mobility. 2
The paediatrician may take on the role of care coordinator. The paediatrician sees patients regularly, but they are also often the first point of contact for family members if a new issue arises. These physicians must liaise with all of the other specialists in order to refer patients in a timely manner, and therefore have a broad overview of the clinical features of Hunter syndrome 2
Hunter syndrome patients often have multiple surgical interventions for frequent otitis media and abdominal hernias, and enlarged tonsils/adenoids. Paediatric surgeons help to manage these symptoms, and consult closely with the multidisciplinary team in order to prepare for the anatomical deformities found in Hunter syndrome. 6
Learn more about the management of Hunter syndrome patients by paediatric surgeons in Information for paediatric surgeons.
Primary care physician (for adult MPS II patients)
The primary care physician may take over the role of care coordinator from the paediatrician as the patient ages, or in rare cases attenuated MPS II may be diagnosed in adulthood. A primary care physician is the first point of contact for a patient if a new issue arises. These physicians must liaise with all of the other specialists in order to refer patients in a timely manner, and therefore have a broad overview of the clinical features of Hunter syndrome.
The transition of care from paediatrician to adult primary care physician may need careful planning to avoid any interruptions in care.
Pulmonologists will manage frequent respiratory and airway problems and therefore work closely with ENT specialists to determine the nature and significance of these obstructions. 1
Learn more about the management of Hunter syndrome patients by ENT specialists in Information for ENTs.
The rheumatologist helps to manage manifestations such as claw-like hands, joint contractures and gait problems. These must be routinely assessed to help plan a physiotherapy programme, or to guide orthopaedic surgeries. 2
Learn more about the management of Hunter syndrome patients by rheumatologists in Information for rheumatologists.
Learn more about the specialist management of Hunter syndrome patients
Other supportive services within multidisciplinary care of Hunter syndrome patients include:
An audiologist can test a Hunter syndrome patient’s hearing, and subsequently fit a hearing aid, if appropriate, and consult with other physicians to manage hearing loss. 2
A behavioural therapist can assess Hunter syndrome patients to determine their neurobehavioural impairment. This could be advantageous for patients, as the behavioural therapist may be inclined to recommend therapies, or inform other physicians of the patient’s ability to cooperate, for example, during the diagnosis of respiratory obstructions. 1,2
Most Hunter syndrome patients exhibit some dental abnormality, including widely spaced, peg-shaped and hypoplastic teeth and delayed eruptions, which dentists may be able to help manage. 1
An occupational therapist will work with the other physicians to determine the difficulties that the patient will have in everyday life, and suggest and implement practical solutions. 2
Physiotherapists work with rheumatologists and the patient’s family to enact a programme of mobilisation, strength and endurance training, enhancement of fine motor skills for the hands, and gait training for the lower limbs, in patients with musculoskeletal involvement. 2
A speech therapist can offer language intervention activities, articulation therapy, and feeding and swallowing therapy, within the limits of what can be achieved due to neurobehavioural impairment. 2
Transitioning from Paediatric to Adult Care
MPS II is a multisystemic disease, hence a multidisciplinary team may be involved in patient management.2 As patients with MPS II reach adulthood, the responsibility for patient care is transferred from the paediatric to adult care team, which may involve an entirely new multidisciplinary team consisting of adult specialists that are each focused on specific symptoms, in contrast to the paediatric care team that often focuses on the overall development and growth of the patient, which can be impacted by MPS II.7,8 In paediatric care, the paediatrician or family practice physician may take on the role of coordinating care among specialists.5 The adult healthcare team also requires someone to coordinate MPS II management and also oversee the transition of care from paediatric to adult care.7,8 This could be a physician, a nurse, a social worker, or another healthcare professional;7 optimally, it would be someone with an understanding of MPS.
During the transition of care from the paediatric team to the adult team, and as the patient begins to take more responsibility over their appointments, it is important to encourage and reinforce the need for regular monitoring of the patient’s symptoms owing to the progressive nature of the disease. 8,9
The biggest problem is the transition coordination. Who is coordinating that? We need a coordinator; someone has to be responsible; someone has to organise, otherwise everyone thinks the other is doing it and nothing happens.
- Dr Christina Lampe, Director of the Centre for Rare Diseases of the Department of Child Neurology, Epileptology and Social Medicine, Center for Paediatric and Adolescent Medicine at the University Hospital of Giessen, Germany
As patients with MPS II reach adulthood, they may wish to become more independent and more involved in decisions about their care.9 Paediatric care in MPS II is family oriented, with parents and caregivers discussing disease management with physicians, whereas adult care is more independent, with patients having more autonomy over their care, and they are the ones speaking to their physicians. 7
The transition from paediatric care to adult care can be particularly challenging for patients with MPS II. Patients with MPS II are often transferred to adult physicians who are not experienced with this rare complex disease, and as they typically have a physical handicap, their family is often involved, which the adult physician may also not be used to. 7 The adolescent patients may also be experiencing problems with puberty, and there are concerns for the patient’s psychosocial needs and maturity. 7
Patient opinions matter. Listen to us.
- Heiko, an adult with MPS II
The goal of a smooth transition is for young adult patients to be guided from paediatric to adult care while maintaining routine review, preserving important clinical information, and incorporating the individual needs of the patient. 7,8 This should be from the culmination of a period of planned and coordinated transition care. 7 It may be useful for the paediatrician and adult physician to discuss the transition. 7 Adolescent patients should also be encouraged to actively discuss their needs and be given opportunities to talk without their parents or caregivers present so they feel more independent. 7 However, the parents, caregivers, and families, who have been taking care of these patients for so long, need to be considered, as it may be difficult for them to give the patient independence. 7
With the large heterogeneity of MPS patients, it is important to remember that not one guideline fits all. 7 Transition of care should be individualised to establish appropriate care plans for the young adult patient. 7,9
- Muenzer J et al. Multidisciplinary management of Hunter syndrome. Pediatrics 2009; 124(6): e1228–e1239.
- Scarpa M et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 2011; 6: 72.
- van der Lee JH et al. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: results of a consensus procedure. Mol Genet Metab 2017; 121(2): 70–79.
- Jones SA et al. Mortality and cause of death in mucopolysaccharidosis type II—a historical review based on data from the Hunter Outcome Survey (HOS). J Inherit Metab Dis 2009; 32(4): 534–543.
- Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 2012; 171(4): 631–639.
- Mendelsohn NJ et al. Importance of surgical history in diagnosing mucopolysaccharidosis type II (Hunter syndrome): Data from the Hunter Outcome Survey. Genet Med 2010; 12(12): 816–822.
- Lampe C. “Transition of Adolescents into Adulthood.” 2014. Presentation.
- Mitchell J et al. Unique medical issues in adult patients with mucopolysaccharidoses. Eur J Intern Med 2016;34:2–10.
- Stepien KM et al. Critical clinical situations in adult patients with mucopolysaccharidoses (MPS). Orphanet J Rare Dis 2020;15(1):114.