Alaskan Malamute Polyneuropathy (AMPN)
Alaskan malamute polyneuropathy (AMPN) is a disorder that belongs to a wider group of disorders known as polyneuropathies. Inherited neuropathies until now have been recognized in 22 breeds of dogs and share many similarities with the Charcot-Marie-Tooth (CMT) group of diseases in humans. Charcot-Marie-Tooth is clinically characterized by muscle weakness and sensory loss. Polyneuropathy in literal translation means “many abnormalities of the nervous system”. Alaskan malamute polyneuropathy was first identified in Alaskan malamutes in Norway in the 1970’s. Since then, numerous cases have been reported in Denmark, Sweden, Finland, Norway and the USA.
Symptoms and characteristics
First symptoms of Alaskan malamute polyneuropathy usually occur in seven to 18 months old dogs. Disorder appears in both sexes. Clinical symotims are exercise intolerance, pelvic limb ataxia, loss of muscle mass, changes in voice due to an affected larynx, problems while swallowing and lack of coordination. More detailed examinations revealed decreased postural reactions, decreased or completelly absent spinal refkexes, laryngeal paresis and muscle atrophy. The severity of symptoms may vary, from mild to severe. First indications of the disorder my be subtle, dog will lay down while eating, dog does not jump up and down while excited ( such as when owner arrives home or before feeding time), slight tremor in its legs and gaint abnormalities. In affected dog, it has been noticed that symptoms appear suddendly, rather that gradually and progressivly. In some dogs, it has been reported a period of six to eight months of more severe symptoms which afterwards lessen but do not dissapear completely. Symptoms in some dogs appear so severe that euthanasia is required.
There are some other spinal or neurological problems that may cause similar symptoms and the Alaskan malamute polyneuropathy may be misdiagnosed. Until 2011, only way to diagnose AMPN was through nerve and muscle biopsies, extensive and expensive examination. This examinations would incluse muscle biopsies, electromyography and nerve conduction velocities. In 2011., a research was made which revealed a genetic mutation responsible for the disorder. Today genetic tests to reveal the carrier of the Alaskan malamute polyneuropathy are available.
Alaskan malamute polyneuropathy (AMPN) is caused by a point mutation in the NDRG1 gene. AMPN is inherited in an autosomal recessive pattern. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the polyneouropathy. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Until now, no treatment for the Alaskan malamute polyneuropathy (AMPN) has been developed, and only way to prevent it, is to breed dogs which are not carriers of the mutation. Defected genes for autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. The only way to find out if there is a chance of getting an affected puppy is genetic testing.
Bruun CS, Jäderlund KH, Berendt M, Jensen KB, Spodsberg EH, et al. (2013): A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy. PLoS ONE 8(2): e54547. doi:10.1371/journal.pone.0054547
Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, et al. (2014) An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs. PLoS Genet 10(10): e1004635. doi:10.1371/journal.pgen.1004635