A brief history of the Forman family and their dealings with Mannosidosis
Our son and daughter, Timothy and Hollie are twins, born 14 November 1974. They were premature (about one month). There were some early indicators that it was more than just a rough start for them, but nothing really clear till they were about one year old and a number of milestones were not met on time.
After another year or two the doctors first diagnosed their condition as Mucopolysaccharidosis Hurler/Scheie. Their condition was not correctly identified as Alpha Mannosidosis until they were 15 years old and blood samples and skin fibroblast cultures were tested in Adelaide Children’s hospital.
In the early years there was a series of regular respiratory infections and ENT problems. Grommet tubes were inserted in their eardrums several times, and tonsils and adenoids removed to ease things for them. Fortunately these problems did reduce in frequency and severity over time. They both have a moderate bilateral hearing loss and use hearing aids to compensate for this.
Their mobility was slightly compromised as youngsters by a mildly unsteady walking gait, and this has become more significant over time. Tim was able to ride a bike till he was about 18 years old, but had increasing co-ordination problems and had to give it up due to frequent falls. He continued with Special Olympics and has taken part in soccer, basketball, athletics, and indoor bowls, but his co-ordination problems have made it difficult for him to continue with active sports, and he gave these up at age 23. Hollie’s mobility was badly affected by a serious arthritis problem, which started in her left hip at about 10 or 11 years of age. It was clearly a direct effect of the mannosisodis, as we were to eventually discover, though didn’t know at the time.
Within a few years of her hip pain developing, Hollie needed a wheelchair for pain relief and ease of mobility. A hip replacement was attempted at age 17 and we had great hope that her mobility would be restored, even though we expected a continuation of the unsteady gait. Unfortunately there was a serious fracture of her femur during the operation, and they were unable to complete the replacement. It seems that her bones were quite osteoporotic, probably the effect of the mannosidosis on her bone development. This fracture and its consequences were devastating for Hollie. What more was life going to dish up to her. One positive result is that she now has no pain in her hip, but the absence of the hip joint makes it too difficult for her to walk unaided, and she is now substantially reliant on her wheelchair. For a time she was able to manage with a walking frame for very short distances, but occasional pain in her knee suggests further problems and it seems safer to keep her off her feet.
We had little access to information and had no clear idea of the real nature of the disease, its progression, or the state of research, until we started to make contact with the Australian and British MPS Societies in 1997. We then made the breakthrough by finding web sites and corresponding with other mannosidosis families in that same year.
The papers on the Internet were the first we had seen which gave any indication of the progressive nature of the condition, or of the bone marrow or other potential treatments. We had regarded their condition as being quite stable for many years now, apart from Tim’s slightly increased co-ordination problems and ataxia as the years passed, and Hollie’s hip and knee problems. The impact of the volumes of information we were now receiving left us with a mixture of excitement and fear, but also hope.
Another major feature of the disorder is the intellectual disability they both have. As with most other problems, this also had a varied impact, with Tim’s being mild to moderate, and Hollie’s moderate to severe. Hollie has very limited language skills, but she has developed some good communication skills to make up for this, and we are able to communicate quite well with her through a mixture of basic language, some signing and a lot of interpretation and guesswork. She went through special schools and special units attached to regular schools, and most of her education was aimed at social skills, communication and social integration. She still lives at home with us and during the day she attends a day activity centre run by IHC, which provides vocational and day activity services for about 3000 adults with intellectual disability, and also has supported housing services for about 2000 people. She is on a waiting list to move into an IHC supported home.
Tim went through school in some integrated classes in the early years and then in special classes in later years. At about 18 years old he started work at a sheltered workshop for people with disabilities. He enjoyed that for several years but at times he found the work tiring. He now tires more easily than he used to, perhaps another effect of the condition. Later on I think he found the work, or the place, boring and wanted a new challenge.
The following year he attended a polytechnic course on Community and Vocational Life Skills, and enjoyed this very much, but all good things come to an end and he is now limited (because of a lack of other options) to attending day activity centres. He has quite good language skills but can have difficulty expressing complex ideas. Tim moved into an IHChouse a few years ago and he shares the home with three other disabled adults, with IHC staff providing support to them to help them manage their lives. He certainly likes the independence he has there, but he is quick to ring us up for assistance when he wants it – and that is usually wanting extra money to spend, or to tape a movie or wrestling programme.The diagnosis of Alpha-Mannosidosis was confirmed when tissue samples were sent to an Adelaide (Australia) hospital for testing. This was when they were about 15 years old and Tim’s co-ordination problems were increasing. Hollie also showed some slight muscle wasting on the hands and wrists. At one stage, amongst a whole new series of tests, scans, x-rays and assessments, we had a diagnosis of motor neurone disease to cope with! That was another major shock to us, though there was great relief a year later when the doctor said he had obviously got it all wrong. It is now clear that they were simply observing some of the typical features of mannosidosis, but interpreting them incorrectly. Quite clearly the doctors were also labouring under a lack of information.
Apart from Tim’s extra co-ordination problems, there does not seem to be any further deterioration for either of them since then. Hollie’s dependence on her wheelchair is regarded as being entirely a result of the failed hip replacement operation. We are confident that if her femur had not fractured, and if the operation had been a success, she would now be walking independently, though the later problems with her knee have further eliminated that possibility.
Looking back over nearly 25 years of dealing with this disease in our family, it is interesting to note that when we had no detailed information on the disease or its progression, the diagnosis had no meaning whatsoever. It was just a very long name that everyone had difficulty pronouncing. At times, perhaps, ignorance was bliss. The availability of all the information we now have has changed many things. It has left us frustrated at times that we didn’t have it sooner – especially when we think that better knowledge may have led to a more cautious approach to Hollie’s hip replacement operation, and perhaps a better outcome.
The most significant thing to deal with now, though, is the information about the state of scientific research, and the potential remedies. We will be seeking more information about bone marrow transplants, so we can consider that as an option if things get any worse for either of them. But we will watch very closely the progress towards enzyme replacement therapy and actively participate in the process of lobbying and information sharing to help speed up the development of this possible therapy, and we encourage every other affected family to do the same.
We will also take advantage of the clinical information about mannosidosis to ensure that the heath care that Tim and Hollie receive is the best there can be.
Update November 1999
As Timothy and Hollie reach their 25th birthday, a number of significant changes have occurred:
Hollie has left home and lives with 4 flatmates in a home supported by IHC. The change has been quite smooth, with mainly emotional issues for all of us to deal with. It is a tough adjustment, but a positive move, we are sure.
Tim’s hearing in his left ear has deteriorated and investigations are underway to determine the cause of this. We fear a permanent deterioration. Fortunately he is still able to hear with a more powerful hearing aid.
Tim’s balance problems are now more significant and we may need to consider mobility aids in the near future. This is hard to accept for such a cool young guy who has participated so much in life, but his limitations do not stop him maintaining enthusiasm for life in general, and a good sense of humour. He still manages a half-day a week job washing cars at his uncle’s car yard.
Bone densitometry checks for them both, show that Tim’s bones are strong but Hollie has poor mineralisation in her hip. Calcium supplements are needed to avoid the risk of fracture. Her bone density is most likely to be poor because of limited weight bearing, rather than the effects of mannosidosis if we do a comparison with Tim, but it has such very different impacts on both of them, that we cannot be sure.
The good news is that ECG tests show that everything is okay with their hearts. The detected murmurs are benign.
Apart from that, things are going well for both of them. They are well settled into a variety of day activities during the week, and enjoy social outings and other leisure activities; shopping being Hollie’s favourite, and movies and TV for Tim. Tim had a minor staring role in a video version of Titanic, being made by a local drama group for people with disabilities, and he is keen to find another part time job. Both are looking forward to what the future holds
Update January 2001
Timothy had to give up his job, as the ataxia has become a more significant problem. He has recently started to use a wheelchair for mobility, to avoid problems posed by a lack of balance and co-ordination. The tough part of watching this transition to a wheelchair has been balanced by the clear reduction in the amount of stress he has to deal with. He is now more calm and relaxed when he has to move about.
The hearing in Tim’s left ear has returned to its previous level. It is a relief that deterioration was only temporary.
Hollie is well settled into her new living situation and seems to be enjoying life and the company of her flatmates. Hollie and Timothy come home once a fortnight for a family weekend. They are pleased to see us, and also happy to return home at the end of the weekend.
After some enquiries about the possibility of bone marrow transplants, and discussions and correspondence with families who have had that procedure for their son or daughter, we have decided not to pursue that option. We accept that the benefits of BMT are less likely to occur in patients at 26 years of age. It is apparent that getting this treatment at an early age offers the best outcome.
It is also clear that enzyme replacement therapy may take many more years to arrive. Dealing with mannosidosis without any therapy will be a reality for Timothy and Hollie for the foreseeable future, but we all look forward to many more years of relatively good health and a good quality of life for both of them.
The chance to make contact with other families and swap information is so important to us. After more than 20 years of isolation we are now part of a worldwide mannosidosis family and we value the contacts and support we can get, or offer to others. We look forward to continued contacts and the day when our combined efforts lead to the development of an effective remedy for this disease. We welcome any contact from other families affected by mannosidosis and are happy to reply to you if you contact John Forman