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|LETTER TO EDITOR
|Year : 2014 | Volume
| Issue : 2 | Page : 210-211
Familial amyotrophic lateral sclerosis from North India: Case report and brief review
Dinkar Kulshreshtha, Ajai K. Singh, P. K. Maurya, A. K. Thacker
Department of Neurology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||02-Dec-2013|
|Date of Decision||01-Apr-2014|
|Date of Acceptance||06-Apr-2014|
|Date of Web Publication||14-May-2014|
Department of Neurology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kulshreshtha D, Singh AK, Maurya PK, Thacker AK. Familial amyotrophic lateral sclerosis from North India: Case report and brief review. Neurol India 2014;62:210-1
Amyotrophic lateral sclerosis (ALS) is predominantly a sporadic disease with only 10-15% familial cases with an autosomal dominant inheritance.  In India, first two cases with familial ALS have been reported by Nalini et al.  We present a family with ALS.
Cases 1 and 2: A 55-year-old male patient presented with progressive asymmetric weakness and wasting of upper and lower limbs of 2-year duration. Initially, he had weakness and wasting in the left upper limb followed by all four limbs over 7-8 months period. For last 6 months, he developed progressive bulbar symptoms with dysphagia, dysarthria and persistent drooling of saliva. Examination revealed dysarthria with tongue wasting and fasciculations and a brisk jaw jerk. Motor system examination revealed both upper motor neuron (UMN) and lower motor neuron (LMN) signs in cervical and lumbar segment with wasting and fasciculations with increased tone in upper limbs and brisk reflexes with a power of Grade 2-3/5 in upper limbs and 3-4/5 in lower limbs with mild asymmetry [Figure 1] and [Figure 2]. Workup for secondary causes of the motor system disorders was negative. Electrodiagnostic studies showed reduced compound motor action potentials and needle examination showed evidence of active and chronic denervation with reinnervation in the form of spontaneous activity and increased insertional activity in first dorsal interossei, biceps, triceps, paraspinal muscles and vastus lateralis on the left side, along with polyphasics, high amplitude motor unit potentials and an incomplete interference pattern. A clinical diagnosis of definite ALS based on El Escorial criteria was made. His father had expired at the age of about 72 years and in the last years; he was bedbound and was restricted to liquid feeds at home. He was not evaluated for his illness and further details could not be elicited.
The proband's son was 37-year-old and came with progressive weakness and wasting of all four limbs of 1 year duration. He had significant neck drop for 3 months. He also had a limb onset of disease with upper limb being involved more than the lower limbs with progressive development of slurred speech. Examination revealed wasting and weakness in upper and lower limbs with severe neck muscle weakness causing neck drop. He had tongue wasting and fasciculations with brisk reflexes in upper and lower limbs including a brisk jaw jerk. He underwent blood investigations including vasculitis workup, serum protein electrophoresis and thyroid profile that were normal. His nerve conductions were normal and electromyography showed evidence of neurogenic pathology in cervical, lumbar, and bulbar segments. He was also clinically diagnosed as definite ALS based on El Escorial criteria.
Familial cases of ALS have co-occurrence of ALS in first-, second- or third-degree relatives and account for 10% of ALS with usual dominant inheritance.  Both father and son in the present report were suffering from definite ALS as per the El Escorial criteria with features of LMN/UMN involvement in three regions viz. bulbar, cervical and lumbar. There was a similar illness in the proband's father though no details into his clinical symptomatology are available. To the best of our knowledge, this is the first such report from North India. Nalini et al. had earlier described two patients with clinically definite ALS from South India.  Genetic testing was not done in these patients.
The identification of mutations in the superoxide dismutase 1 (SOD1) gene in 1993 triggered the first major wave of molecular research in ALS.  SOD1 is a ubiquitously expressed protein that catalyzes the detoxification of superoxide. More than 160 mostly dominant missense mutations in SOD1 are associated with ALS. Mutant SOD1 toxicity is mediated through several mechanisms like protein misfolding and oligomerization.  Only about 20% patients with familial amyotrophic lateral sclerosis have SOD1 mutations. Several novel ALS genes have been identified over the past few years.  Chiò et al. have reported that GGGGCC hexanucleotide repeat expansion of the C9ORF72 gene was the most common mutation in their large cohort of patients with familial ALS of Italian, Sardinian, and German ancestry. These patients display prominent cognitive dysfunction and a bulbar onset. They also show the phenomena of anticipation in successive generations, as seen with repeat expansion diseases. 
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[Figure 1], [Figure 2]