Molybdenum Deficiency Produces Motor Nervous Effects That Are Consistent with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS)–motor neuron disease (MND) is divisible into 6 familial and 10 sporadic syndromes (1). Familial syndromes are also recognized in animals, namely, dogs, cattle, rats, and mice. This article is concerned with the most common form of ALS, sporadic Charcot ALS (SC-ALS). This form is of particular interest because it does not occur in any animal as a complete disease; instead, each of its three parts can occur as separate syndromes in sheep, horses, and cats. It is possible that physiological differences between these animals and humans could explain this separation. In addition, an understanding of the etiology of each animal syndrome could reveal a common predisposing factor that is responsible for generating the complete disease. Molybdenum (Mo) deficiency has recently been demonstrated as the predisposing factor for two of the animal syndromes and the third has a pathogenesis that is consistent with Mo deficiency. This raises the possibility that Mo deficiency is the predisposing factor for SC-ALS. Two of the three animal syndromes referred to occur in sheep and are associated with Mo deficiency. Both produce specific motor nervous effects not known to occur in any other sporadic, adult onset, animal disorder. The first is xanthosine motor neuron syndrome (XMNS) (2). In this chronically progressive and irreversible syndrome, an asymmetric muscle weakness develops in one pelvic limb and sometime later, in the corresponding thoracic limb. The muscle weakness is accompanied by atrophy, and dysfunction is restricted to particular extensor muscles. The commonest presentation of SC-ALS is similar to this and involves asymmetric weakness and atrophy of some muscle groups in either upper or lower limb. Asymmetric muscle weakness in mammals is produced by a very precise upper motor dysfunction that can only emanate from the basal ganglia in animals, such as sheep, and from the basal ganglia and motor cortex in humans (3–5). Xanthosine ingestion during Mo deficiency is the only etiology so far demonstrated in a mammal, which can produce this type of progressive and irreversible asymmetric muscle weakness. The second Mo deficiency-associated sheep disorder is inosine motor neuron syndrome (IMNS) (6). In this chronically progressive and irreversible syndrome, a brain stem-generated bulbar muscle weakness develops together with a brain stem-generated respiratory muscle weakness. These two dysfunctions lead to difficulty in vocalizing, swallowing, and breathing, including a reduced forced vital capacity. In SC-ALS, 30% of cases present with bulbar signs and in the remaining 70% …