Early onset sporadic ALS – phenotype of eight patients

The history and phenotype of sporadic patients suffering from amyotrophiclateral sclerosis is of major interest since this group of patients may be of major importance for the screening for genetic risk factors. We describe here eight ALS patients with an age of onset in their teens; an autosomal-dominant pattern of inheritance was excluded by their family history.

Clinical phenotype and progression of the individual disease courses have been studied over the last ten years. We report the symptomatology, typical laboratory investigations and discuss the possible underlying mechanism. Two etiological factors have so far been identified.

Mutations in the Cu/Zn superoxide dismutase (SOD) gene and the alsin gene putatively encoding a ras GTPase. These mutations, however, account for fewer than 10% of patients with familial ALS. None of our patients presented here, has one of these two known mutations.

We also examined other clinical features – predominant upper motor neuron, frontal dementia, bulbar vs. spinal onset, male vs. female, bladder disturbances (relationship to HSP/upper motor neuron disease). We assessed time course and survival and we report diseases other than ALS in the family.

We are actively studying these (and other) patients and their families (surviving parents and earlier generations) and screen them for genes

presently considered atypical for ALS (dynactin, spastin) and perform a genome-wide screen to look for genetic instability.