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 Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر (Re: معاوية الزبير)
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نسأل الله أن يشفي حمد ابن الأخ الصديق عمار شفاء لا يغادر سقما
أعرف وأقدر كثيرا ما بذله عمار وهو مذهل وقد استحق عليه ثناء من أطباء عالميين كبار وشهادة من مستشفى حمد بالدوحة.
وأدناه ما سطره عمار عن هذا المشوار الذي نسأل الله أن يكلل بالشفاء التام لفلذة كبده حمد.
The first and only known patient alive who suffers from congenital glutamine synthetase (GS) deficiency: a journey for finding a diagnosis.
Written by
Ammar ajool
Doha Qatar
[email protected]
Tel 009745137270
Revised and reeditied by doctor kamal hassan
Consultant pediatric gastroentrology
Hamad medical corporation
Doha qatar.
The diagnosis confirmed by a (DNA) study done by
Dr. med. Johannes Häberle
Division of ####bolism
University Children's Hospital
Steinwiesstrasse 75
CH-8032 Zürich
The father of the patient is a journalist working for Aljazeera news channel in Doha Qatar wrote:
On 2/3/2007 my son Hamad was born at Hamad General Hospital in Doha, Qatar. Because we had a previous son who died in 2005 at the age of five years after a failed stem cell transplant in Jordon for mucopolysaccharidosis (MPS), we were enormously worried through out Hamad’s pregnancy. Within minutes after giving birth, my wife assured me on telephone, that the new baby was not affected by MPS Maroteaux-Lamy syndrome. She could tell the difference in the appearance between an affected child and a normal one. So my wife and I were greatly delighted that our new baby was, apparently, normal.
Unfortunately, he started to have brief seizures on day 13. He was crying relentlessly which was extremely painful for us. Various kinds of anti seizure drugs (phenobarbitone Keppra (levetiracetam) tegretol and phenytoin failed to stop it. In fact, the opposite effect happened and the seizures increased in both the frequency and the duration. The worst thing was that the baby went into more relentless crying.
As a family, and against medical opinion, we decided to stop the medications. The seizures improved but did not stop. The crying ameliorated. By the age of three months, we noted that Hamad’s development was obviously delayed and he had no eye to eye contact.
We took him to the hospital again and the Doctors found that his serum ammonia was relatively elevated (80 - 170 umol/l).They told me that there was no evidence of a urea cycle defect to justify the hyperammonemia. So they sent blood samples to Heidelberg hospital in Germany to investigate for a wider range of ####bolic diseases but all the results came back normal.
As a worried father, I went to Google for help. I spent more than 5000 (five thousand) hours on it, trying to find a solution. Immediately after putting his data on Google, I noticed that his high ammonia in the presence of low glutamine was an unusual phenomena because an elevated ammonia level is usually associated with a high glutamine level with some rare exceptions (propionic academia, methylmalonic academia). This finding surprised me and led me to do more extensive search. I found an interesting study titled (Hepatic Glutamine Synthetase Deficiency in Fatal Hyperammonemia after Lung Transplantation) http://www.annals.org/cgi/content/full/127/6/446
The author, Tuchman, built his study on the question “why was the plasma glutamine level low to normal with elevated serum ammonia in those patients”. I know that my child had neither undergone lung transplantation nor received chemotherapy. The paradox continued to exist: why did Hamad had elevated ammonia and a low glutamine levels in the blood. The doctors in both Heidelberg university (Germany) and Hamad hospitals could not explain this extra-ordinary situation.
Moreover I discovered that my son's Cerebrospinal fluid (CSF) glutamine was also low. I wondered that the low glutamine in both the plasma and CSF may indicate a systemic glutamine deficiency so I went to the WEB tracing a disease named or related to ( congenital glutamine deficiency ) . I found that there were only two cases reported in the medical literature and both died during the neonatal period
http://content.nejm.org/cgi/content/full/353/18/1926
http://content.nejm.org/cgi/content/abstract/353/18/1926
Although I gave the doctors the paper of the research of the two babies, no one supported the idea that Hamad could have this disease (congenital glutamine synthetase deficiency). I continued emphasizing on: why there is low glutamine in the presence of high ammonia. so The German doctors and others from USA. Canada, and some European and Middle eastern countries, during a medical conference in Doha in November 2007, decided to repeat the Cerebrospinal fluid (CSF) amino acid test at the Heidelberg hospital labs because they did not believe the finding of an elevated ammonia with a low glutamine. Surprisingly, the results again showed the paradox of a low glutamine and elevated ammonia.
After that I tried to explore the possibility of the other causes of hyperammonemia. We excluded the possibility of the urea splitting organism as a cause. Porto-systemic shunts were another possibility and this was suggested by a hepatic angiogram (ct with contrast). My son underwent a trial of blocking those potentially very small shunts by CT-guided injection of glue in India with a temporary response. Later he underwent right hepatectomy in Egypt with no significant improvement.
I went back to my doctors arguing that the low glutamine synthetase may be the major factor of the child's disease. I wrote to doctor Häberle who diagnosed the only two cases of (GS deficiency) in the world. He kindly accepted to do a genetic test for Hamad, my wife and myself in Zurich children’s hospital. While we were waiting for the results I was searching for enzyme replacement therapy. But in order to enhance the deficient enzyme in my son I convinced the doctors to give him dexamethasone (DEX) which is a well known inducer of glutamine synthetase. A four months trial of DEX, helped the child to avoid hospitalization and to become more active and aware of the surroundings and less irritable. Biochemically, the ammonia levels dropped significantly during dexa treatment plus antibiotics (around 42 umol/l). I think that the Dexamethasone saved Hamad’s life during those difficult times but I was aware that it was not a long-term solution because of its dangerous side effects.
I continued reading about glutamine synthetase and ammonia. An interesting finding that I also came across was an invention on the (world intellectual property organization ) wipo page, stating that the antidepressant (tianeptine) and the vaso-protector (naftazone) are selective ligands of glutamine synthetase, they are regulators. Again, I managed to convince the doctors to give him tianeptine and withdraw the dexamethasone . They agreed after they had discussed the issue with the head of the pediatric department. It was a very difficult battle to convince them to do so. Now Hamad is doing well with tianeptine. He began to interact with the surroundings. We are very optimistic. But we know that, a real change in Hamad’s brain needs many years. He needs to rebuild the eroded myelin sheath, to enhance both glutamine and glutamate production and to wash out the toxic extra cellular glutamate in his central nervous system.
We are now in the stage of tracing the enzyme replacement therapy. However even before the diagnosis was confirmed, I had received a huge encouragement from doctor Anil Dhawan, the professor of hepatology at kings collage hospital in London, who tried to convince my doctors in Doha to help my son by contacting the specialized Centre to explore the possibility of a trial of enzyme replacement.
In the next coming days, hamad will be given ( glutamine supplement ) as mono therapy, under a special protocol designed by doctor haberle who diagnosed him. We hope this helps hamad .
Also I can not exclude bone morrow transplant as a last resort for saving my child’s life, since stem cell therapy can afford away enabling hamad to produce a healthy (GS). If I decide to do a stem cell transplant for him, I will choose the ( nonmyeloablative transplant) because it is more safe due to its reduced chemo regemen. .
However now the recent DNA study on Hamad, his mother and myself has proved what I had been suggesting for about two years, that the lovely baby is having congenital glutamine synthetase deficiency.
On Wed, 10 Jun 2009 my doctors here in Doha Qatar received this e-mail from Dr.Harbele:
Dear Tawfeg
We now finished the investigations in your patient AGOL Hamad Amar with suspicion of GS deficiency: the patient is homozygous for a novel mutation in the GS gene and the parents are carriers of this. I’m confident that the mutation is disease causing because it affects an amino acid that we previously carefully investigated and now know that it is relevant for normal GS function. You will get the written report soon.
The finding is very interesting for various reasons:
1. This is the first and only known patient alive who suffers from GS deficiency. As you know the only 2 other patients described with GS deficiency died as newborns.
2. You write the patient suffers from chronic encephalopathy and seizures and has severe changes on cerebral MRI. Knowing the diagnosis and the very low glutamine levels substitution of glutamine should be considered as treatment for the patient. This I regard as not dangerous because the patient has a normal urea cycle and should not get any problem with the substitution of glutamine. However, this should be discussed with the family (who I did not yet inform on the result of the mutation analysis). From what I know (because the father was in contact with me in parallel with you) I expect the family to agree to the compassionate use of glutamine in the child. This should then be done in a standardised and scientific way and we should discuss how to proceed. I would be very happy to plan the compassionate use together with you, we should define the dose of glutamine (starting and maintenance dose), the intervals to check amino acids in plasma and urine and endpoints of our trial (frequency of seizures, neurodevelopment etc.)
3. It would be great if we could improve the clinical situation of the patient and hereby proof the principle of treating moderate GS deficiency.
Please let me know your thoughts on this.
Best regards,
Johannes
**********************************************************************
PD Dr. med. Johannes Häberle
Division of ####bolism
University Children's Hospital
Steinwiesstrasse 75
CH-8032 Zürich
……………………………………………………………………………………………………………………………………………………………………………………………
I remember that morning. Those were historic moments in my life. The feeling of a great victory was mixed with joy. Now the door is opened to a new hope for Hamad’s treatment. At that those moments I gazed to my child reminding his suffering through out the tow years without proper diagnosis and correct medications. I promised him to continue having my full support without limitations. The Doctors here were so surprised. They spoke to me in very encouraging words.
What is (GS) deficiency?
It is a painful, destructive disease. The manifestation varies greatly between the only three documented cases in the medical literature. However in Hamad, as it is considered a moderate deficiency, the cells of the body are not able to produce the sufficient enzyme (glutamine synthetase also called glutamate-ammonia-ligase). This enzyme is involved in the ####bolism of ammonia and glutamate and the production of glutamine. Without this enzyme the central nervous system can not wash out the toxic ammonia. Ammonia is washed out by the urea cycle enzymes in the various organs of the body except in the brain where the main detoxifier of the ammonia is the enzyme glutamine synthetase. Hamad is not able to produce proper and enough amount of this vital substance because of the defective (GS) gene. There for, mainly his central nervous system is affected. But in the more severe forms of this disease, as reported in the two cases by haberle et al, many of the body organs may be affected and severe brain malformations occur. In Hamad case , the brain (MRI) was normal till the age of seven month, when hypomyelination started to be obvious. At the age of eleven month, thinned corpus callosum was noticed.
Important lessons:
I do need to say that a journey of two years in the hospitals and the pediatric intensive care units were not easy with a child repeatedly connected to the mechanical ventilator for long periods. When Hamad was 7 month old, the doctors gave the child Midazolam. After days they came to me saying that the child is affected by one of the worst central nervous system diseases called burst suppression. They were very clear in saying that the condition is evident by the EEG video recording and that it is incurable and the prognosis is extremely poor. They advised me to consider stopping the life support equipment. I totally refused to discuss ending my child’s life.
I did some search again in the internet to get more information about burst suppression. I remember that midnight I was quite devastated, tired and exhausted but I suddenly became full of energy when I found articles describing burst suppression induced by midazolam. I went to the doctors with the papers next morning .They stopped the midazolam and soon afterwards the burst suppression disappeared. That was well documented in the hospital’s records both clinically and by ( EEG ).
The child is now at home improving and his mother deals smartly with his tracheostomy and gastrostomy tube feeding
I wrote this story hoping that it will be read by the families as well as doctors so that both sides realize the importance of good listening and communication.
To the parents, I say that if they work hard they can find solutions for their children’s health problems. Parents should share the responsibility with the doctors. A doctor usually deals with thousands of conditions but parents deal with one case. Community support groups in the internet can be extremely helpful. However, even if there is no such a groups, like our case, the internet is still rich with many good information sites. So our son Hamad is the only living child with GS deficiency, and he is defending himself courageously.
To the doctors I say: please give the parents the chance and listen carefully to what they say as long as those parents are following the rules of the orthodox of medicine in their search. My story demonstrates the fact that the patient with one of the rarest diseases in medicine has been diagnosed by some one from out side the medical community. Actually this some one was his loving father.
Ammar ajool
Doha Qatar
Tel 009745137270
Revised and reeditied by doctor kamal hassan
Consultant pediatric gastroentrolog
Hamad medical corporation
Doha qatar.
Thanks for:
PD Dr. med. Johannes Häberle
Division of ####bolism
University Children's Hospital
Steinwiesstrasse 75
CH-8032 Zürich
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| العنوان |
الكاتب |
Date |
| صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | معاوية الزبير | 04-30-10, 09:58 PM |
 Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | سيف النصر محي الدين محمد أحمد | 04-30-10, 10:30 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عثمان كباشي | 04-30-10, 10:34 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | Tragie Mustafa | 04-30-10, 10:42 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | سلمى الشيخ سلامة | 05-01-10, 00:01 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | Adil Osman | 05-01-10, 08:39 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | Adil Osman | 05-01-10, 08:48 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | الحاج حمد الحاج | 05-06-10, 07:09 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | Elsheikh Mohd Aboidris | 05-06-10, 08:02 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | MOHAMMED ELSHEIKH | 05-06-10, 08:24 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عماد موسى محمد | 05-06-10, 09:50 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عماد موسى محمد | 05-13-10, 12:25 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عماد موسى محمد | 05-13-10, 06:50 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عبد الفتاح زوما | 05-13-10, 09:06 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عماد موسى محمد | 05-14-10, 06:00 PM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | محمد سنى دفع الله | 05-15-10, 08:14 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | معاوية الزبير | 05-16-10, 03:29 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | علي الكرار هاشم | 05-16-10, 07:12 AM |
| Re: صحفي سوداني يذهل الأطباء بتشخيص مرض ابنه النادر | عماد موسى محمد | 05-16-10, 11:51 AM |
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