Storage Diseases and Inborn Errors in Metabolism
Robert J. MacKay
Inherited Myoclonus of Peruvian Paso Foals
Inherited myoclonus was described in two Peruvian Paso foals that demonstrated myoclonic contractions of the musculature in response to auditory or tactile stimuli.1 These contractions were sustained with repeated stimulation.
One foal could not stand without assistance, and the other had a “bunny-hopping” gait in the pelvic limbs. Analeptic drugs and tranquilizers were ineffective for controlling this condition. Inherited myoclonus was associated with a specific deficiency of spinal glycine receptors, which are responsible for synaptic inhibition in the CNS. Glycine is a major inhibitory transmitter providing reciprocal inhibition via type Ia afferent fibers and interneurons, as well as recurrent inhibition on motor neurons via Renshaw cells.Congenital Encephalomyelopathy in Quarter Horses
Congenital encephalomyelopathy has been described in Quarter Horse foals.2 The condition occurred in three foals born to two different mares and three unrelated stallions. Signs were present at birth and included recumbency and coarse tremors of the pelvic limbs. When the foals were assisted to stand, the hindquarters bounced off the ground. Thoracic limb function appeared normal; however, patellar reflexes were exaggerated. The affected foals were bright, alert, and responsive and had intact pain perception. They had no gross CNS lesions. Microscopic lesions included spongiform degeneration and axonal swelling of the spinocerebellar spinothalamic tracts within the medulla and spinal cord.
Lavender Foal Disease (Coat Color Dilution Lethal)
Lavender foal syndrome is an autosomal recessive disorder of Arabian foals that has been recognized for many years but reported only as recently as the mid-2000s.3,4 Lavender foal syndrome is characterized by a dilute coat color, episodes of opisthotonos, hyperresponsiveness to touch, limb paddling, and rapid, uncontrolled eye movements.
Affected foals are unable to assume sternal recumbency or stand. Despite the incapacitating neurologic signs, animals with lavender foal syndrome are able to vocalize and usually have a strong suckle response. The important feature of this condition that distinguishes it from neonatal encephalopathy and other causes of neonatal neurologic dysfunction is the dilute hair color. In a few cases, the color is the striking iridescent silver to pale lavender hue, as suggested by the name. Coat color dilution lethal may be a more appropriate name, however, because many affected foals exhibit other dilute coat colors, including pewter (pale slate gray) and pale chestnut (pink), and because complications from neurologic abnormalities invariably lead to death or necessitate euthanasia by approximately 72 hours. Abnormal findings at necropsy are nonspecific and minimal. A single base pair deletion in the MYO5A gene is responsible for lavender foal syndrome.5,6 This deletion results in a frame shift and truncation of the protein at a premature stop codon 12 amino acids beyond the deletion. Loss of MYO5A disrupts melanosome trafficking and endoplasmic reticulum transport in cerebellar Purkinje cells, thus leading to the clinical signs of cerebellar seizures. Reported allelic frequencies are 5.2% among Egyptian Arabian horses in the United States,6 1.62% among European Arabian horses, and 0% among European Thoroughbred and Standardbred horses. Testing for the MYO5A gene mutation is available commercially and is performed on plucked mane and tail hairs.Overo Lethal White Syndrome
Overo lethal white syndrome is an inherited syndrome of American Paint foals from parents with the frame overo coat pattern.7,8 Affected foals are totally or almost totally white and die within days from complications of intestinal aganglionosis.7 Aganglionosis is characterized by a complete lack of submucosal and myenteric ganglia from the distal small to large intestine. Foals with vero lethal white syndrome are homozygous (designated OO) for a dinucleotide mutation, which causes an isoleucine-to-lysine substitution at codon 118 in the gene for endothelin receptor B.9,10 Although heterozygotes for the lys118 mutation (nO) are mostly frame overos, the mutation is also found at lower frequency in other white patterned horses, including tobianos and solid pattern breeding stock.11 The mutation is not usually found in breeds without white pattern variants, although overo lethal white syndrome was reported in the offspring of a registered Quarter Horse. Genetic testing is the only reliable method for detecting carriers. Plucked mane or tail hairs are submitted to commercial laboratories for testing.
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