Correct Dia

I have three daughters. All were born apparently normal my elder daughter aged 10 Years  is normal (not effected), younger daughter name Shafia, aged 6 years is effected (diagnosed SMA) and  third one name Rameen, who is about 4 years old also diagnosed SMA at the age of 2 years.

My second daughter Shafia aged  6 years diagnosed as spinal muscular atrophy (Type III) at the age of 2 years, based on her  abnormal EMG reports.
EMG Findings:  Motor NCVs in normal limits/ Distal motor latencies normal in nerves / Amplitude of  compound muscle action potentials are borderlines in nerves / F-waves normal / Needle EMG shows denervation pattern (fibrillation /positive sharp waves) in Rt bicep, Rt ist dorsal interosseous, Lt Hypothenar, Rt qaudricep and Lt tibialis anterior muscles.

She  was born apparently normal and begins to walk at the age of 1 year, improvement seen time to time.   The first signs of Atrophy were recognized  when she was  18 months old, feel weakness in her  shoulders and arms, difficulty in climbing stairs, difficulty in getting up from sitting on the floor and unable to run. She also not talks clear words as other children of her age.

At the age of 2.8 years she  has been tested for SMA using the exon 7/8 gene deletion SMN test. The results were negative for SMA.  
SMA PCR (Blood test Spinal Muscular Atrophy):
Final Report: Deletion of Exon 5 not detect in NAIP gene.
Deletion of Exon 7 and Exon 8 not detected in SMN1 gene.
Interpretation: The given blood sample is found to be NORMAL for NAIP and SMN1 gene.
(All other blood test and MRI are normal and no family history at all.)

Due to negative result of SMN deletion test doctors advised for muscle biopsy for her correct  diagnose. So At the age of 4 yr. 5 months her muscle biopsy performed in Neuromuscular Diagnostic Laboratory, Singapore.  
muscle biopsy:
Conclusion:   Very large grouped atrophy and fibre type grouping together provided clear evidence of chronic and severe denervation, with collateral reinnervation. In the clinical context. These findings may be compatible with an anterior horn cell disorder, such as milder forms of SMA, or with a chronic peripheral neuropathy. However, further clinical correlation and correlation with point mutation gene studies for SMA is advised. This is because the additional features of speech difficulty noted in the patient are inconsistent with SMA.

S.M.A. Point Mutation test:
Analyses:   Genomic DNA was extracted from the patient’s blood sample and screened for deletion and intragenic point mutations in the telomeric survival motor neuron gene (SMN1) by PCR amplification   followed by RFLP-bassed deletion analysis, and direct DNA  sequencing.
Result:        No deletion or intragenic  mutations of SMN1 were identified.

On view of above detail my daughter’s beginning symptoms, her EMG and the muscle biopsy findings diagnose as SMA type 3 but the SMA PCR and Point Mutation test  reports are negative for SMA.  So we confused about her correct diagnose, as children with SMA have a very slowly progressive, or non-progressive at all but my daughter condition is totally different (progressive).  She  diagnosed for SMA at the age of 2 years. At that time she can sit, stand, get up from the floor, walk independently and climb stairs with support and not need braces or a walker. She was non-progressive and also feels little balance and walking improvement during first year of diagnose (between 2 & 3 years of age)  but after 3½ year of age, her problem / Disease  observed very quick  progressive. Now she is 6 years old and in previous 2½  years  many big changes experenced gradually as under:










1) Now she can sit with  support only and  cannot  stand or walk with or without support,   As 2½  years before she can sit, stand, get up from the floor, walk independently and climb stairs with support and not need braces or a walker.

2) She has totally loses her speech ability. Present position is that she cannot speak a single word as before she can talk so many words and sentences. An observational assessment established low-facial tone, poor bilabial closure, open mouth at rest, poor approximation of articulators during speech attempts. Her blowing is week she cannot make bubbles or use vessel. She also  not drinks water or any other liquid with the straw as before she can.

3) 1 year before we observes some hearing problem on her and find severe high frequency hearing loss in the “BERA” test. She can hear little with support of hearing aid. Her hearing loss also observing progressive day by day.

4) Shape and size of muscle getting weaker day by day.

5) No Weight gain from previous 3 years. Present weight is 12 kg (diet almost average).

On appearing   so many problems together some doubt occurs about the correct diagnose of my daughter. As  SMA is a non progressive / very slow progressive diseases but in my daughter case all these problems come together and In a  short period of just 2 ½ years she get totally paralyze from a good walking condition. Mentally she looks normal (Not observing any mental loss on her). No problems with swallowing or any respiratory problems at present. Her Head, mouth size and eye sides are normal. As per my knowledge SMA only affect the muscles of body bellow the neck. The face muscles (Hearing / Speech not effected) by SMA type 3.

My another younger daughter name Rameen, aged 4 years also diagnosed as spinal muscular atrophy (Type III) at the age of 2 years, based on symptoms like feel weakness in her  shoulders and arms, difficulty in climbing stairs, difficulty in getting up from sitting on the floor and unable to run. Her abnormal EMG reports findings are almost same as my second daughter. She has been tested for SMA using the exon 7/8 gene deletion SMN test and the results were negative for SMA.

Rameen’s present condition is that she can sit, stand, get up from the floor with some support, walk independently and climb stairs with support and not need braces or a walker. She is very active and intelligent and also starts going to a normal children school from previous 7 months. Her new observing problem is difficulty in speech.  As before 3 months she can talk very well and speak very clear words and sentences but from few weeks experiencing problem and gradually unable to talk verbally and feeling difficulty in speaking sentences as well as words. Now she cannot talk clear 2/3 words sentence. This new problem also observing more progressive day by day.

As my both daughters  SMA observed (often rapidly) progressive, I have few questions related to there correct  diagnoses. As per my information SMA dose not cause hearing loss as well as the Speech problem is also not a symptom of SMA. On other side SMA is a non progressive / very slow progressive disease but in my daughters case all these problems come together. On appearing so many problems together some doubt  occurs  about the correct diagnose that either there diagnose as SMA Type 3 is correct or  possibility of  some other neuromuscular condition. Is there any possibility of “White Matter diseases”?    

You are requested to please give your valued opinion / comments as all your remarks are very important for me and my daughters’ neurologist to get the correct diagnose.  

Sorry for so much detail and thank you for your help.

Yours truly,


Faisal.