Wednesday, November 2, 2011

Muscle Dystrophy (MD), Duchenne Muscle Dystrophy (DMD), Limb Girdle Muscle Dystrophy (LGMD)

This article is written by a non-specialist (father of a patient) and of course meant for all those poor souls who are just been diagnosed with Muscle Dystrophy (MD) with the high CPK (Createne Phospho Kinase) presently anxious and wanted to know more on What next???

Courtesy : MDA

The first step for an individual with high CPK is to find which MD is it. So, having categorizing the Muscle Dystrophies, I shall narrate the ways to diagnose which is the dystrophy, which is a major challenge and I have succeeded in achieving the results. The central idea of this article is to pay high emphasis on the Diagnosis part. Of course, I too DO NOT have an answer to What next??? However, I shall certainly try to help those who are in dark about What could be Next?

Muscle Dystrophy (MD) is a genetic disorder related disease. It is a progressive in nature and hence the patient suffering from MD will not see dramatic changes (in degradation) in his/her health. How fast or slow it progresses will depend on which type of disease it is. It is for this reason, I would urge every individual who is "suspected of MD" but type is not known, MUST find an answer that which type of MD he/she is suffering. Many doctors and experts made fun of me by asking what will you do after knowing the MD. My humble answer to them is please and please keep yourself on this side of the table and think.... Would you not like to know how dark is the future for you...How far would like to WALK in the future? Finally, tomorrow if there is cure based on the mutation then you must know Which is the mutation.

Till today, the MDs are characterized by clinical manifestations; while the future direction is: reclassification of the MD into disorders defined not by clinical characteristics but by the specific genetic mutations. After the huge progress in genetic sciences in the past 2-3 decades the MD are now assessed at the genetic level by finding the genetic mutation. However, historically, the first documentation and detailed study was done on Duchenne Muscle Dystrophy (DMD); being the most dreaded one and found mainly in males at a tender age. It is caused due to the mutation in dystrophin gene resulting in the dystrophin deficiency. Another variant of the same type is called Becker MD (BMD).

The second major category is due to the sarcoglycans called Limb Girdle Muscle Dystrophy LGMD which further categorised to LGMD- 2C, 2D, 2E, 2F and with mutation in Calpain gene it is called LGMD-2A, while mutation in dysferlin would lead to LGMD-2B. While both DMD and LGMD belong to autosomal recessive disease; meaning neither of the parents could have these symptoms; the other type is called autosomal dominant (LGMD-1A, 1C..) where the disease is basically percolated downwards from their elders to the children. There are few more types of MDs, less known as they occur far less in number which run into 10-12 types, are again assigned due to the mutation in various genes.

The first step in diagnosis is to go for a simple CPK Test. This would certainly tell about whether the patient is suffering from some leakage of material createne from their muscles. Pray to god that your CPK should be within 100 (counts); the moment it is in few hundreds or thousands, doesnt matter how large it all means that you are into the MD domain.

Though the doctors would go for few other tests called EMG (ElectroMyoGram) test etc to rule out few other class of defects. However, the most reliable test so far (NOT ANY MORE) is the muscle biopsy test. From Indian point of view there are few Governmental hospitals/institutes (Sree Chitra Thirunal Institute, Trivandrum, Kerala, NIMHANS-Bangalore, few other..) which would do the muscle biopsy at NO cost, but few other private hospitals would charge as per their standard.

The philosophy to be followed is to rule out few major MD by muscle biopsy tests before getting into Genetic Tests. The genetic test for DMD is straight forward (can be done at CCMB, Hyderabad, INDIA) and charges are very nominal in India. However, there is no other place as of now (July-2011) in India which performs reliable genetic test for MD (Please refer to the latest development brought out in a small NOTE at the bottom).

As such, the genetic tests (any where in the world) are very expensive; to rule out one type of mutation they may charge few hundred US dollars; the cost of these tests are slowly coming down as the technology matures with faster sequencing making its headway.

Here are few places in the world who are taking up the genetic tests for MD (by no mean this is the authoritative list; also the mail-ids are only representative of persons in charge at the time of writting; by no mean an authentic information):

1. Athena Diagnostics Inc., Worcester-MA
2. Emory Genetics Laboratory, Ph No (USA): 404-778-8499

National Insitute Neurosciences, Tokyo, 187-8502
Dr. Narihiro Minami:

1. Leiden University Medical Center, Leiden, Netherlands
Prof. Bakker:

2. Prof. Sabina Gallati, PhDHead of the Division of Human Genetics
Specialist in medical genetic analysis FAMH
Dept. of Paediatrics; Inselspital; CH - 3010 Bern; Switzerland

January: 2014
Thanks to Dr. Ashwin Dalal of CDFD , India; he has helped me in tracking every laboratory in the world which takes up the gene sequencing of various muscular dystrophy; this information is distributed by none other than the most trusted research entity in USA, the NIH, the site is: Genetic Testing Registry. For example, in my case of LGMD-2A, the site gave me 27-centers across the globe which are taking up the gene sequencing for CALPAINOPATHY.