Alpha-mannosidosis

What is alpha-mannosidosis?

Every cell in your body has structures called lysosomes, which is where the cell breaks down the waste products from cellular activity.  The lysosome is often referred to as the cell’s recycling center because it processes this waste material into substances that the cell can utilize.  Lysosomes break down this unwanted matter using enzymes, which are highly specialized proteins.  These enzymes are essential for breaking down the waste products.

Luke is missing an enzyme called alpha-mannosidase, which means his cells are not able to break down sugar waste products.  Because the sugars are not broken down, over time the waste builds up in the lysosomes, and the lysosomes grow.  This growth of the lysosomes causes the cells not to function correctly, affecting the cells differently and leading to a variety of seemingly unrelated symptoms.  Because the lysosomes store these waste products, the class of disorder is known as a “Lysosome storage disorder”.

How did Luke get it?

Alpha-mannosidosis is an inherited genetic disorder.  Both of Luke’s parents (Robin and Kevin) are carriers of a single copy of the defective gene, but they are not affected by the disorder.  Luke received both copies of the defective gene (one from each parent) meaning he does not have the right gene (MAN2B1) for his body to produce the alpha-mannosidase enzyme.  

How common is it?

It is extremely rare.  The occurrence is somewhere between 1 and 2 in 1,000,000 people.  As far as we know, Luke is one of 3 cases in Canada and the lab that tested this has not seen a case for 15-20 years.  This means that most of the doctors we are dealing with have not seen this condition before.  We have had some contact with other families who have children with alpha-mannosidosis, in England, Canada the US and New Zealand. 

What are the effects of Alpha-mannosidosis?

The disorder affects every cell in Luke’s body, so the symptoms are varied and affect many aspects of Luke’s health and development.  Different cells respond to the build up of waste product in the lysosomes in different ways.  The disorder is progressive, so the effects become more severe over time.  Because there are so few cases and the progression is different for every case, we don’t know what the rate of this progression will be for Luke.  The most important effects on Luke are:

  • Hearing:

The cells in Luke’s hearing centres are impacted, and he has a moderate-severe hearing loss.  He wears hearing aids to help with this.

  • Ear Fluid:

Luke is susceptible to fluid build up in his ears, which further impacts his hearing.  He has had 4 surgeries to implant tubes in his ears to help drain the fluid, which has helped significantly.

  • Blood:

Luke has reduced numbers of white blood cells, meaning he has a weakened immune system.  He is more susceptible to infections and gets colds and infections more often, and for longer than normal.

  • Bones:

Luke’s bones build up more quickly, and so he has a bigger head, forehead, prominent sternum and thicker bones throughout his body.  He is also at risk for osteoporosis, which we will need to monitor.

  • Muscles:

Luke’s muscles are weaker and have lower muscle tone, meaning he is not as athletic as his peers.  He has some gross-motor, co-ordination and balance issues, and gets tired easily.  His fine-motor skills are also affected, making it harder to hold a pencil, cut with scissors and perform other fine motor activities.

  • Joints:

There is a build up of material in the joints, as well as destruction of cartilage over time.  In later years, the joints become painful and arthritic and Luke may need a wheelchair for mobility.

  • Brain:

The cells in the brain are also affected.  The cerebellum is affected, affecting balance and co-ordination.  Luke will also have some degree of mental impairment, which will affect his learning and require extra support at school.

  • Life expectancy

People with alpha-manosidosis, have a reduced life expectancy.  Some children with the severe form die in infancy, while those with a milder form live well into adulthood. 

Is it treatable?

There is no cure at this time; treatment is limited to reducing or controlling the symptoms. Because the condition is so rare, there is not a lot of information on this condition, or the treatment.  Currently there are two ideas for potential treatments:

  •  Enzyme replacement therapy:

The missing enzyme is artificially manufactured and then intravenously introduced into the body, eventually getting to the cells and allowing the cells to break down the waste products.  This therapy has been developed for some other lysosome storage disorders, but has thus far only been tested on mice for alpha-mannosidosis.  At present, it appears that this therapy is many years away for treating alpha-mannosidosis.  It is also not clear that the enzyme would be able to reach the cells in the bones or the brain, since the enzymes are very large molecules.

  • Bone marrow transplants:

This is currently the only therapy that has been tried for treating alpha-mannosidosis, and we are aware of only 24 patients worldwide that have had it done to treat alpha-mannosidosis.  Blood is manufactured in the bone marrow, and the purpose of this treatment is to replace Luke’s bone marrow, with bone marrow from a donor, capable of producing the alpha-mannosidase enzyme.  Luke’s bone marrow would be destroyed with chemotherapy and/or radiation therapy, and then  bone marrow from a donor would be implanted (like a blood transfusion) to take the place of Luke’s bone marrow.  The donor’s bone marrow would then start making blood cells with the missing enzyme, allowing Luke’s body to break down the waste products in his cells.  It appears there has been some success with this treatment, but it is a very invasive and risky procedure.  We are in contact with a number of families that have had this procedure and are discussing the outcomes that they have experienced.

What can we do?

We are getting excellent care at BC Children’s hospital.  We are seeing many doctors from many different departments to discuss various options for treatment of the disorder and the symptoms. Luke will need extra support at school, which we are applying for through his school.  The most important thing is to understand what Luke has, and how it affects him, and being sensitive to the special needs he might have.  He is still the happy, loveable boy we all know, and we don’t want this to change the way he is treated, or how people act with him.

29 Responses to Alpha-mannosidosis

  1. Aunt Cynthia says:

    Thank you for letting us know. This must be a very difficult time for all of you but, I know that both you (Robin) and Kevin are extremely strong people. You have each other and of course, your two wonderful boys. The family will support you, just let us know what we can do for you! Take care and please, keep us informed.

    Aunt Cynthia & Uncle Trevor

  2. Matz Family (Manchester) says:

    Hi Kevin & Robin,
    Just heard about Luke from my folks. Our thoughts are with you and your family.
    Please keep us informed.
    Gavin, Jodie (& Mica)

  3. Deepest prayers and a cornucopia of all good Karma to each and everyone in your wonderful family. Steven

  4. Pam Ritchey says:

    Amazing! I signed up for Google Alerts of Alpha Mannosidosis so I could receive updates on new discoveries, and they sent me a link to your site.
    I’m grandmother to two young girls who had BMTs for AM. I was with my daughter and her husband throughout most of the hospitalization and isolation times at Columbus, Ohio, Children’s Hospital.
    I’ve done a lot of research on Alpha Mannosidosis and written a few newspaper articles about it.
    The girls were diagnosed as having a mild form of the severe infantile type and are four and five years post BMT now with few problems.
    I’d love to hear from you and put you in contact with my daughter in PA.

    • Thanks Pam – We’d love to get in touch with you and your daughter’s family. How are things going for the girls since the bone marrow transplant?

      • Pam Ritchey says:

        Kevin, Great to see your post! The girls are doing good. Christina had her BMT when she was three; Kayla was less than two. I have lots of info and the articles I’ve written for the newspapers that I’d love to send to you.
        Could you please send me your email address?

      • Whitney Webb says:

        Hello. My name is Whitney and my daughter was just diagnosed with AM last week. I’m trying to find information on it and the success of doing BMT for AM but I’m not finding a lot of information. I would lik to get into contact with families that have undergone the BMT. Please reply back so I can get into contact with someone that shares the same diagnosis. thanks whitney

  5. Heather Strack says:

    We are rooting for you and your family. Luke is a very special young man surrounded by endless love and devotion. We will be praying for your successes.
    Keep smiling Luke

    Love the Strack’s

  6. Diana Pringle says:

    Chris let Dave and I know what was happening with Luke and your family!!! I finally got around to looking at your website for Luke!!! Just signed up for updates as well. Too bad we’re in PG or else could help out in some way. Of course we’ll be praying for you!!! Will continue to monitor this journey you’ve had to take and hopefully we’ll see each other at some point over the next while!!!! Love ya, Diana

  7. Janice Manfron says:

    I just heard about Luke and the road he has ahead of him. I picture his smiling face when I think of him, he is a very special boy. He always had a special place in my heart during his years at preschool and will continue to do so. If any of you need anything at all please contact me. I am in the neighbourhood close by if you need “any” extra support. Thinking of you all and best wishes in the coming days.
    Love,
    Janice

  8. Sandi Robertson says:

    Cheryll let me know about Luke today and I’ve had a read through your very informative website. I’m so glad you’ve had some fun, family times this summer before this intense BMT journey begins. I’ve thought a lot about Luke this summer, especially on his birthday, which looked like fun. I’ll miss seeing him on Sept 7th, but will be thinking about him, and send you all my caring thoughts.
    Take Care, Sandi

  9. Mary Andreola says:

    My thoughts and prayers are with you all.

  10. Clare Duffett (Scheppening) says:

    Hi Kevin. I was so moved when I read about your little boy and can’t imagine what you guys are going through right now. The journey you have been on looks really hectic and I’m sure the next few weeks will be pretty difficult too. I will really pray for Luke (and Andrew) especially as he undergoes the bone marrow transplant next week and pray that you guys will know God’s incredible peace. I will definitely be checking your blog and will keep praying for an amazing miracle!
    Sending lots of love, Clare, Gus, Joseph and Rachel xx

  11. Kathy Shepard says:

    Hi! Our son (Matt) had a Bone Marrow Transplant in January 97. He was six then and we just celebrated his 20th birthday! We live in Pittsburgh and traveled to Minnesota for the transplant. It is very hard when most doctors have never heard of such a disease – so I wish you the same path that Matt took (somehow always being in the right place at the right time). The night before he went in for his work-up week (which is what it sounds like you’re going through now) he got a mohawk haircut and as I read your email – it sent chills up my spine and it seemed like yesterday. I will follow Luke’s story and keep you all in my prayers!

  12. Helen Scott ( Bennett) says:

    Thinking and praying for you all at this time. We hope and pray that God will guide the whole medical team involved in Luke’s care. We are also thinking of you all during this hard time of decisions. Hoping that all goes well with whatever you decide.

    Rhett, Helen , Emma and Matthew

  13. Alisa Duffett (Hide) says:

    Hi Kevin – and your incredibly strong family
    I have just picked up on your blog via a friend on FB, and had no idea of what was all going on with you. I do hope for you all much strength and patience at this particular time with both your boys. “There are years that ask questions, and years that give answers”.
    Your family will be in my thoughts and will check back regularly to see how things are going.

  14. Elizabeth Bongolan says:

    Jan Fretter – sent us the link this am. Andrew, Luke, Mom and Dad – we are praying for all God’s mercies to be showered on you today – and we will continue to pray for you… love, Elizabeth – (Smith-Bongolan)

  15. Parveen Mann says:

    Hi Robin
    Thank you for sharing this with us and allowing us to support you and your family. James, Taren, Asha and I are all sending good vibes to Luke.

    Saw this quote a few years ago and I hope it provides some encouragement for you all:

    What lies behind us and what lies before us
    are tiny matters compared to what lies within us.
    ~Ralph Waldo Emerson

    Parveen

  16. Kirsten, Dave & Kathryn says:

    Sending you support & good wishes. We’d love to drop dinner by for you on exceptionally busy days; so drop a line when it would be of help. It’s something that lightens the load for you & is easy for us to do; so please don’t hesitate to take us up on it. Also, let us know if you need transport or care for Andrew when you’re busy with Luke’s schedule.
    Kirsten, Dave & Kathryn

  17. Julie Bosch (nee Hide) says:

    Hi Kevin and fam

    Just heard from Alisa, my sister, about Luke and seen your most informative website as to what your family is going through. Our thoughts and prayers are with you. Be strong in the Lord and lean hard on him. So good to hear about the super medical treatment that has been available to you.

    love Julie, Dave, Kerryn, Matthew, Nathan and Stephen

  18. David Knight says:

    Hi
    Kevin’s mom directed me to the website. It is a hard thing to have a child with a such a rare disorder and I hope that there will be an improvement as a result of the transplant. May God be with you, your family and particularly Luke.
    David Knight, South Africa.

  19. Hilary says:

    Your son Luke looks like such an amazing boy! Thank you for sharing his story. We have a son who is 1 year old and will be getting tested for a similar condition. He has hydrocephalus and is impacted in similar ways as what you describe here with his development. We live in Ontario.

  20. June Ditson says:

    Greetings from Abbotsford,
    Robin, we heard of your family’s struggle from Jan on FB, and it took a while for me to realize it was your little boy. I am praying for you all as you walk this journey, that you will know the peace of God that transcends all understanding. Good news that his enzymes are so much higher!
    love
    June

  21. Bev Krieger says:

    Hi Robin and Kevin,

    I was at Chris and Jen’s for Thanksgiving and heard about Luke. Kurt told me the results of the BMT last week. I am so thankful that his enzyme levels are so high. I pray that each step of the way will bring even more amazing results. He is such a handsome little boy. I will be praying for you.

    Love,
    Bev Krieger

  22. Sarah Ali says:

    Hello Kevin Chaplin,

    I want to say thank you for the information you have shared here, and I wish good health to you, Luke and your family. I know the journey you have all been through.

    My son Yusuf, who was born in March 2008, was diagnosed with Alpha-Mannosidosis on 2nd October 2009 at Milton Keynes Genral Hospital, after lengthy tests and appointments. He was then put through more appointments and testing at Great Ormond Street Hospital for Children in Central London, this is the only Hospital in Britain that will treat Alpha-Mannosidosis.

    Then, on 28th November 2010 he went in for his 1st BMT, they used an un-related cord blood donor, it failed. Yusuf rejected the cells, after 9 weeks and 2 days he came home sick and needed so many medicines and has to have milk through the night on a pump. This is still the case now. We are so disapointed and downhearted, but Yusuf still has a smile which my husband and I treasure so much.

    We are going to try again, this time I will be the donor. I couldn’t before because, unplanned I fell pregnent with our 6th child, this was upsetting for me because I let my son down.

    I want to give you this informaiton because this time round Great Ormond Street Hospital are going to do the Bone Marrow asperant (my spelling may not be correct) differently. Even the chemopherapy drugs have changed.

    What will happen is Yusuf will go into hospital in October sometime, dates are not yet confirmed, he will begin his chemopherapy. I will then be given a drug known as GCSF, this boosts cell growth in the bone marrow helping the cells spread from marrow into my blood. I will have this drug each day for 5 consecutive days. Then I beleive it will be on the 6 th day I will be taken to another hospital where I will be hooked up to a blood transfusion machine. An IV line will be placed into each of my arms, then, from one arm blood passes into machine, it then takes the cells, then passes the used blood back into my other arm. Bone Marrow is then collected without having surgery to remove it! It is then, the marrow has what it needs done to the cells, bagged then passed into Yusuf’s hickman line which will be fitted the day after he first arrives at GOSH. This treatment will be a related live blood (bone marrow) cell donor. This treatment should work better for Yusuf.

    I hope I have explained it easily. I don’t know if Yusuf would actually be cured or if this only helps a little. He already has bone abnormalities, hearing loss, weak joints, infections, face, skull and forehead are prominent. He has shown symptoms since birth.

    Im sorry if this message is a bit long, I wanted to give you the information so it can be passed onto other families as I dont know how to create a web page, Im not very good at computers.

    Thank you for sharing Luke’s story, it has been very helpful and informative.
    Sending good health and best wishes to you all. Sarah, Milton Keynes, United Kingdom.

  23. Anne Denneen says:

    We stumbled upon your site a few months ago and have been inspired by Luke’s story. My son Liam is going through BMT (day +13) now for MPS II. We are hoping and praying for results like Luke’s. Liam’s sister was his donor. Would love to hear from you personally. Feel free to email. -Anne

  24. Lynn bulmer says:

    Hello my son has just been diagnosed with this, any other information would’ve greatly appreciated

  25. Whitney Webb says:

    I found your site very helpful. My daughter was just diagnosed with this disorder yesterday so I’m trying my hardest to gain knowledge of it. I would like to hear more about everything and if he ever got the BMT. My daughter is 4 and she has been progressing in her speech and I just want her to keep progressing and not start regressing. We live in Texas but are willing to travel wherever to get we the treatment she needs. Thanks!

  26. wk72408 says:

    Hello! I got a notification with your comment about your son recently getting diagnosed. My name is Whitney, and my daughter, Ryleigh was recently diagnosed about 3 months ago and we are currently getting ready to have a bone marrow transplant. I know how scared and overwhelmed I was when I first found out about my daughter so I would like to help you also with any information. You can contact me at whitney_webb@att.net and we can set something up to talk on the phone if you would like. Also my daughter has a website, http://www.ryleighfightsback.webs.com and a Facebook page, http://www.facebook.com/ryleighfightsback. Can’t wait to here from you!
    Best Regards,
    Whitney

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