Hi Tatyana-

Welcome to LAL-D Aware.  I'm a genetic counselor in the USA, and I worked with enzyme replacement therapy for several lysosomal storage conditions, including CESD. 

We followed two patients who received Kanuma for over a year, and I know several other patients receiving Kanuma. It is well tolerated, normalized cholesterol  levels and decreased liver enzymes for our patients, and even appeared to reverse some liver disease.  Enzyme replacement therapy (ERT) also helps people feel better in general. It is too early to say for Kanuma, but for other lysosomal storage diseases with long term treatment data available, it helped children grow better so they reached normal stature like their parents, and prevented many of the more serious complications. It also helps alleviate gastrointestinal symptoms which can be severe for some patients.

Most patients see an elevation in serum cholesterol soon after starting Kanuma when the trapped cholesterol is initially freed from the liver, and then in a few weeks cholesterol levels normalize.

If your son was symptomatic when he was a toddler do not postpone starting enzyme replacement therapy, since this is a progressive condition and it is important to prevent disease progression before serious complications or liver failure occur. There is no downside to enzyme therapy other than that it is expensive or in the rare instances when a patient has a hypersensitivity reaction (allergic like reaction) but this is more common with the infantile form when patients have zero working enzyme activity.  For CESD, most people have some residual enzyme activity and so their bodies do not recognize the enzyme as a foreign antigen as the infants sometimes do. 

The infusions take some adjusting to at first but soon become very routine. For small children it helps to have a port placed so that venous access is easy and painless, and so the children are not afraid to have the treatment.  Children can walk around, play and eat while receiving the infusions.

As for special diet, low fat diet is probably a good idea, but will not really impact the disease. For infants a special formula called MCT is recommended but for children normal diet is fine.

If you have other children they have a 1 in 4 chance of also having LAL-D so should be tested. If you will have more children you may wish to talk with a genetic counselor. 

Please do not hesitate to let me know if you have any questions or would like additional information.  I'm sure you will hear from patients about their experiences soon!

I hope your son is on the way to recovery, and feeling fine.

Best wishes,

Donna

Dear Tatyana-

it must be so frustrating that most doctors do not know CESD very well if at all.

I will do my best to answer your questions, but it could help to know more about Vanya. Did Vanya have genetic testing or only the enzyme test? Do you know the changes in his LIPA gene? Do you know the his enzyme activity results? 

CESD is progressive in all patients but the rate depends on the DNA mutations and the amount of enzyme activity. People with essentially no enzyme activity have severe symptoms, but it is not always easy to predict (for example if there is more enzyme activity but it does not get to the right part of the cell where it is active).  

The most common mutation in Europeans is called E8SJM-1 (exon 8 splice junction mutation, also called  c.894G>A  or p. del S275_Q298. We have a lot of names for the same change in the gene)! E8SJM has been seen in Eastern European patients, so it may be the mutation in your family. This is a mild mutation because it has about 10% of normal enzyme activity, but can still have a fairly severe childhood onset with high cholesterol, enlarged liver and spleen, anemia, low platelets, bruising, nosebleeds, respiratory infections, vomiting and diarrhea. So no picnic (to say the least). Children with this genotype can have liver fibrosis at an early age, but may not develop more serious liver disease (cirrhosis or liver failure) or heart problems until adulthood. There were only about twenty or so children reported who had two copies of E8SJM-1 so information is limited . Some patients with one copy of E8SJM and a different second mutation had serious liver disease, and heart problems.  

Patients with two copies of E8SJM are likely to survive to adulthood. For patients who do not have two copies of E8SJM,  some patients have a rapidly progressive infantile form, with almost no enzyme activity, but Vanya does not have this form, because they do not survive past the first year of life. Some people with CESD require a liver transplantation or die in childhood, often by the early teens to early twenties. Some people survive until their 40s or 50s and one patient survived to be 82 years old. If you know the mutations and or enzyme activity, I may be able to tell you if another similar patient was reported. I hope Vanya two copies of E8SJM so he will likely live a long life. 

Enzyme replacement therapy with Kanuma is still new, but so far very effective. I'm optimistic that it will stop the disease from progressing, so hopefully Vanya will get Kanuma and live a normal healthy, happy life, other than spending an hour twice a month getting the enzyme therapy. This becomes very routine after the first few times.   

I am at the word limit so will send more in part 2!

Part 2-

Regarding your question about waiting to start Kanuma, this is not an easy question to answer. Even if I knew the mutations, I would be hesitant to gamble with his health. There was a baby reported who had a stroke at age two years. We do not have long-term data to say with certainty that Kanuma can prevent this, but we know that it normalizes cholesterol which should decrease risk of a vascular event. I would do everything possible as soon as possible. If he is not feeling well, Kanuma could give him a healthy happy childhood instead of having to go through so much illness.  Does Vanya have symptoms? Vomiting, nose bleeds, respiratory infections or frequent diarrhea? Kanuma can make these symptoms go away often  after only a few months. Children with CESD can have delayed puberty and short stature. Although there is no long-term data for Kanuma, other lysosomal storage diseases with delayed puberty and short stature had prevention of these with enzyme replacement therapy, so probably Kanuma will do the same for CESD. If you can travel to another country where you can get ERT , I would do so.  I'm sure it's not so easy...

Until he can get Kanuma, I have seen patients do much better if they take a cholesterol lowering medication called actigall (ursodiol) and welchol (colesevelam). These are not so expensive, so I hope Vanya can take these until you can get him on Kanuma. Lipid lowering medications do not help as much with liver disease, and statins may add to the liver problems, but the bile acids actigall and welchol may be your best options until he can receive Kanuma.  

As for the next pregnancy, if Vanya's mutations are known, prenatal testing is very accurate. Prenatal testing can also be done on enzyme activity  through amniocentesis or chorionic villus sampling, but there can be overlap between enzyme activity for carriers and and unaffected people with two working copies of the gene so few labs offer this. If a person has one working copy of the LIPA gene and one non-working copy that has a mutation they will never develop symptoms but may still have lower than average enzyme activity. If the mutations are known you can also have preimplantation genetic diagnosis, In vitro fertilization is done and two cells of the embryos are tested and only unaffected embryos are implanted. In experienced centers this is very accurate.

Sorry to write such a long response. Your questions are very important and you must be extremely worried. Please be optimistic that Vanya will get better, and once receiving enzyme replacement therapy can live a long, healthy life. We had a patient in her mid fifties who was diagnosed as a child, so it is very possible that he will be okay. 

If you want to let me know about Vanya's DNA mutations, enzyme activity, symptoms or if you have any more questions, please feel free to email me here. I will send you my contact information as well in case you would like to talk.  

Donna

Dear Tatyana, my Name is Gabi. Thanks for jour Interest of me.

My English is not so good, but I hope you understand me.

I`m 54 Jears old and Im very sick. For to Years ago I become Kanuma. Kanuma gives me Live (Life) With that are my pains not so strong. My eat is a diät . I eat a lot of Bananas, My body dont like " long - chains fat"!!! I cook with Coconut oil. These eating is expensive. But it helps.I live in Germany. Here is this disage very rare and many Doctors dont no this Disage. I cant work with that and I havent Money to live a good Live(Life). Also I must look of them and I havent help. Sometimes i wish, Im dead...

your Boy have a big Chance!!! With Kanuma you gets him help. Please look to become this Kanuma very reguarly!!! Show, to eat and gives him not so many eat with "long -chain fats"... A little bit its okay!I wish you and your Family all the best. A fine Christmas-time and a happy new Jear ;)