Large animal Neurology Ch. 31 - Congenital, familial, and genetic disorders

Question 1

What is Citrullinemia?

Answer 1

An acutely fatal cerebrospinal neurologic disorder affecting Holstein-Friesian calves due to a deficiency of arginosuccinate synthetase (AS)

Caused by a point mutation in the gene coding for AS, leading to elevated plasma citrulline and ammonia levels.

Question 2

What are the clinical signs of Citrullinemia in affected calves?

Answer 2

Dullness, facial twitching, blindness, head pressing, aimless walking, tremor, stupor, seizures, opisthotonus

Signs typically develop within 1-7 days of age and lead to death within several hours to 4-5 days.

Question 3

What is the normal range of plasma citrulline concentration?

Answer 3

0.19 to 0.07 mmol/L

Affected calves show elevated concentrations of 2.25 to 1.64 mmol/L.

Question 4

What is the genetic basis of Citrullinemia?

Answer 4

A point mutation in the gene coding for arginosuccinate synthetase

This results in a deficiency of this urea cycle enzyme.

Question 5

What is Maple Syrup Urine Disease?

Answer 5

An aminoaciduria affecting newborn calves of the Polled Shorthorn and Polled Hereford breeds

Characterized by accumulation of branched-chain amino acids due to a deficiency of mitochondrial branched-chain alpha-keto acid dehydrogenase.

Question 6

What are the clinical signs of Maple Syrup Urine Disease?

Answer 6

Progressive dullness, ataxia, difficulty rising, paddling of limbs, terminal recumbency, opisthotonus

Often results in death by 1 week of age.

Question 7

What is the mode of inheritance for Maple Syrup Urine Disease?

Answer 7

Autosomal recessive disorder

Caused by mutations in genes coding for the branched-chain alpha-keto acid dehydrogenase (BCKD) complex.

Question 8

What syndrome was identified in newborn Gelbvieh-cross calves?

Answer 8

Status spongiosus of white matter

Characterised by diffuse, moderately severe, bilaterally symmetrical, status spongiosus with Alzheimer type-II cells throughout the white matter of the brain

Question 9

What causes cerebellar hypoplasia?

Answer 9

Congenital viral infections and toxins during fetal development

Some breeds have been suspected of having a hereditary form, likely autosomal recessive. Often associated with other defects such as hydranencephaly and arthrogryposis.

Question 10

What are the signs of congenital cerebellar hypoplasia in calves?

Answer 10

Stable signs of cerebellar dysfunction, such as ataxia and head tremor

Signs may abate with time.

Question 11

What is cerebellar abiotrophy?

Answer 11

A presumed deficiency of a vital, trophic (nutritive) substance in cells (cerebellar neurons in this instance), which results in the degeneration and depletion of cerebellar pyramidal (Purkinje) and granular cells that may be regarded as premature apoptosis.

Typically affects Arabian foals, Gotland ponies, and Yorkshire piglets.

Question 12

What is the typical age of onset for cerebellar abiotrophy in Arabian foals?

Answer 12

Between 1 and 6 months of age

Rarely observed at birth.

Question 13

What are the histological findings in cerebellar abiotrophy?

Answer 13

Degenerative Purkinje and granular cells, swollen Purkinje axons

The cerebellum typically becomes small, often less than 8% of total brain weight.

Question 14

What is the outlook for animals affected by cerebellar abiotrophy?

Answer 14

Grave for moderately to severely affected animals

Some with late onset and mild signs may recover.

Question 15

What is the genetic basis for cerebellar abiotrophy in Arabian horses?

Answer 15

Compromised expression of the candidate gene MutY homolog (MUTYH)

Involves autosomal recessive inheritance.

Question 16

What are the signs of bovine familial convulsions and ataxia?

Answer 16

Calves are born recumbent and unable to rise, then demonstrate one or several convulsive episodes usually in the first few days of life. After standing, or
when first observed at days to weeks of age, a wide-base posture, ataxia, and a mild intention tremor are seen in calves that survive several of these episodes.
Signs abate, and by 12–15 months the convulsive episodes rarely occur such that by 2 years of age survivors are clinically normal.

Question 17

What is the typical outcome for calves with late onset and mild signs of the disorder?

Answer 17

Some can recover to an acceptable state

Some affected sheep and ponies have survived for many years.

Question 18

Which breeds of calves are commonly affected by bovine familial convulsions and ataxia?

Answer 18

Aberdeen Angus, Angus cross, Polled Hereford, Charolais

Affected at birth or by a few months of age.

Question 19

What is the maximum percentage of calves in a herd that may be affected by this disorder?

Answer 19

Up to 30%

Affected calves may show waxing and waning signs of cerebellar disease.

Question 20

What is the primary clinical feature of ovine cerebellar cortical degeneration (daft lamb disease)?

Answer 20

Difficulty rising and wide-based, ataxic movement

Affected lambs may die without significant nursing care.

Question 21

What differentiates DLD-A from DLD-B in daft lamb disease?

Answer 21

DLD-A shows histologic cerebellar lesions; DLD-B does not

Question 22

What congenital syndrome is characterized by agenesis of the caudal cerebellar vermis?

Answer 22

Dandy-Walker syndrome

Can involve cystic dilation of the caudal ventricular system.

Question 23

What are the signs associated with Arnold-Chiari malformation in calves?

Answer 23

Maldeveloped cerebellum and elongated cerebellar tonsils protruding through the foramen magnum

Often associated with other malformations like hydrocephalus.

Question 24

What are the clinical signs of congenital myoclonia in Hereford calves?

Answer 24

Inability to stand, hyperesthesia, muscle tremor, myoclonia, periods of tetanic spasms

The gestational period is shortened compared to unaffected calves. Calves remain bright and alert but recumbent from birth.

Question 25

What genetic mutation is associated with congenital myoclonia in Hereford calves?

Answer 25

Nonsense mutation in the gene for the αlpha-1 subunit of the inhibitory glycine receptor ## Footnote Leads to a significant reduction in spinal cord glycine receptor levels by 80-90%, also resulting in overexpression of cerebral γ-aminobutyric acid receptor function.

Question 26

What clinical feature characterizes lavender foal syndrome?

Answer 26

Episodes of tetanic muscle contractions with opisthotonus ## Footnote The coat color is an iridescent silver to pale lavender. Foals are bright but recumbent from birth.

Question 27

What is the genetic basis of spinal dysmyelination in American Brown Swiss calves?

Answer 27

Mutation in the SPAST gene ## Footnote Resembles hereditary spastic paraplegia in humans.

Question 28

What breeds can be affected by Congenital Tremor Syndrome?

Answer 28

Saddleback pigs, Landrace pigs, Jersey calves, Shorthorn calves, Angus-Shorthorn calves ## Footnote Symptoms include tremors of limbs and head at birth.

Question 29

What is the typical progression of symptoms in animals affected by Congenital Tremor Syndrome?

Answer 29

Signs are usually not progressive; animals may improve over weeks to months ## Footnote Affected neonates may have difficulty gaining weight.

Question 30

True or False: Affected animals in Congenital Tremor Syndrome typically show weakness.

Answer 30

False ## Footnote Ataxia is present, but usually without weakness.

Question 31

What is the primary symptom observed in animals affected by congenital tremor?

Answer 31

Fine to jerky tremor, usually of the limbs, trunk, and head ## Footnote Affected animals may also exhibit a base-wide stance and a hypometric or rocking-horse gait.

Question 32

What are the common names associated with congenital tremor in different species?

Answer 32

* Shaking Piglets * Dancing Pig Disease in pigs * Hairy Shaker Disease in lambs * Jittery Calves

Question 33

What is Hog cholera/swine fever, and what syndrome does it cause in piglets?

Answer 33

A disease caused by a Pestivirus that causes congenital tremor in piglets, often with additional systemic and nervous syndromes ## Footnote It is especially associated with cerebellar disease.

Question 34

What is Type-A congenital tremor in pigs associated with?

Answer 34

Variations of cerebellar hypoplasia and cerebrospinal hypomyelinogenesis found at necropsy

Question 35

What is Campus Syndrome in Pietrain piglets characterized by?

Answer 35

High-frequency tremor while standing that resolves with recumbency + difficulty walking ## Footnote This condition is likely inherited but lacks evidence of neural or muscular lesions.

Question 36

What is Border Disease, and what are its clinical expressions?

Answer 36

* Hypomyelination * Barren ewes * Abortions * Stillbirths * Birth of small and weak lambs

Question 37

Which virus is associated with Border Disease?

Answer 37

Border disease virus, a Pestivirus

Question 38

What are the clinical signs of congenital tremor in Holstein-Friesian calves?

Answer 38

* Congenital tremor * Occasional tetany * Degrees of incoordination * Absent menace response * Nystagmus

Question 39

What are the lesions associated with congenital tremor syndrome in calves?

Answer 39

* Hypomyelination * Status spongiosus * Myelin vacuolation * Alzheimer type II astrogliosis

Question 40

What type of lesions have been observed in congenital tremor syndrome in Eland Antelope and Santa Gertrudis calves?

Answer 40

Degrees of hypomyelinogenesis and cerebellar hypoplasia

Question 41

What is the typical clinical presentation of encephalopathy in neonatal Swaledale lambs?

Answer 41

Rapid onset of dullness, seizures, seizures, and death by 3-14 days of age

Question 42

What are the notable histopathological findings in encephalopathy of neonatal Swaledale lambs?

Answer 42

* Neuropil rarefaction * Capillary proliferation * Astrocyte necrosis or depletion * Adjacent white matter shows vacuolation and variable astrocyte activation * Lesions prominent in the tegmentum, olives, and thalamus

Question 43

What congenital brain malformations are associated with forebrain malformations in calves?

Answer 43

* Agenesis of the corpus callosum * Holoprosencephaly * Anencephaly

Question 44

What is the recommended approach for treating seizures in foals?

Answer 44

Consider maintenance anticonvulsant therapy if multiple generalized seizures occur over several days ## Footnote Generally self-resolves by a few months of age

Question 45

What is narcolepsy, and what are its types in humans?

Answer 45

* Narcolepsy Type-1 (NT-1) * Narcolepsy Type-2 (NT-2)

Question 46

What is the characteristic feature of narcolepsy with cataplexy in foals?

Answer 46

Paroxysms of collapse and excessive daytime sleepiness

Question 47

Which breeds of foals have been observed to exhibit narcolepsy with cataplexy?

Answer 47

* Suffolk foals * Miniature Horse foals * Morgan foals * Shetland ponies * Welsh ponies * Appaloosa foals

Question 48

Describe the typical syndrome of narcolepsy with cataplexy in foals

Answer 48

* Stable pattern of sleepiness and recumbency depending on environmental stimuli * Normal inter-ictal period * An attack may progress from buckling at the knees without falling to sudden and total collapse and areflexia, usually with the maintenance of some eye and facial responses and normal cardiorespiratory function * Each recumbent episode may last up to hours ## Footnote Persists for life

Question 49

What is the syndrome that develops in Appaloosa foals related to sleepiness?

Answer 49

Inherited narcolepsy with cataplexy (NT-1) ## Footnote The syndrome typically leads to a stable pattern of sleepiness and recumbency, persisting for life.

Question 50

What are the characteristics of a typical cataplectic attack in foals?

Answer 50

Buckling at the knees, sudden collapse, areflexia, maintenance of some eye and facial responses, normal cardiopulmonary function ## Footnote Episodes may last up to hours if undisturbed.

Question 51

How is narcolepsy with cataplexy diagnosed in animals?

Answer 51

Observing rapid eye movements, absence of spinal reflexes during recumbency, excessive daytime somnolence ## Footnote A clinical diagnosis is needed to conform to human criteria.

Question 52

What is a key biochemical defect associated with narcolepsy?

Answer 52

Abnormal levels and activities of hypocretins (orexins) ## Footnote These neuropeptides are involved in sleep and arousal states.

Question 53

What is juvenile onset narcolepsy without cataplexy?

Answer 53

Persistent excessive daytime sleepiness with paroxysmal sleep attacks but no loss of muscle tone ## Footnote This condition has been observed in Warmblood, Icelandic, and Thoroughbred foals.

Question 54

What characterizes sporadic idiopathic hypersomnia in adult animals?

Answer 54

Excessive daytime sleepiness with sleep attacks occurring while standing, without profound loss of muscle tone ## Footnote This syndrome is multifactorial in etiology.

Question 55

Define hydrocephalus.

Answer 55

Increased CSF volume within the cranium, specifically enlargement of the ventricular system ## Footnote It can be congenital or acquired, often associated with other brain malformations.

Question 56

What is hydrocephalus ex vacuo?

Answer 56

Hydrocephalus occurring with pre- or postnatal loss of brain tissue ## Footnote This condition may result from obstruction of CSF drainage.

Question 57

What are the clinical signs of hydrocephalus in animals?

Answer 57

Failure to thrive, somnolence, aimless activity, poor suck reflex, poor swallowing, central blindness ## Footnote Signs can be subtle even with minimal cerebral mantle.

Question 58

What is hydranencephaly?

Answer 58

Presence of fluid-filled cavities within the brain lined by astrocytic processes ## Footnote It is often associated with secondary hydrocephalus ex vacuo.

Question 59

What are the clinical signs of hydranencephaly?

Answer 59

Somnolence, central blindness, and signs from accompanying congenital cerebellar dysfunction ## Footnote These signs are particularly evident in calves.

Question 60

What is the primary condition observed in Limousin cattle encephalopathy?

Answer 60

Widespread degenerative lesions in white matter regions of the brain ## Footnote Signs include hypermetric ataxia, peripheral blindness, and weight loss.

Question 61

What distinguishes Simmental cattle encephalomyelopathy from Limousin cattle encephalopathy?

Answer 61

Simmental encephalomyelopathy involves necrosis in brainstem and spinal cord gray matter without lesions in cerebral white matter ## Footnote Symptoms progress to marked ataxia and recumbency.

Question 62

What is a suspected cause of encephalomyelopathy in Angus calves?

Answer 62

Multifocal, symmetrical, necrotizing encephalomyelopathy ## Footnote Symptoms include ataxia, nystagmus, and seizures.

Question 63

What are lysosomal storage diseases?

Answer 63

Rare diseases from inborn errors or acquired defects in metabolic enzyme pathways ## Footnote They often result in the accumulation of undigested substrates within lysosomes.

Question 64

What are common signs of lysosomal storage diseases in animals?

Answer 64

Aimless wandering, seizures, aggressiveness, central and peripheral blindness ## Footnote Onset may be at birth or heralded by mild signs of ill thrift.

Question 65

How are many lysosomal storage diseases inherited?

Answer 65

Autosomal recessive mode of inheritance ## Footnote Genetic testing can help identify these conditions.

Question 66

What mode of inheritance is often represented by inherited diseases?

Answer 66

Autosomal recessive mode of inheritance ## Footnote This pattern is commonly seen in genetic disorders.

Question 67

What testing method is used to reduce the frequency of certain inherited phenotypes?

Answer 67

Testing for abnormal protein expression followed by a nonbreeding/slaughter policy ## Footnote This method helps in controlling genetic disorders in breeding populations.

Question 68

What is a characteristic of toxin-induced lysosomal storage diseases?

Answer 68

They provide insight into metabolic pathways involved in inherited and acquired disorders ## Footnote They help explain individual susceptibility to toxicities.

Question 69

What are congenital anomalies in portal circulation associated with?

Answer 69

Failure of the liver to complete metabolic and detoxifying tasks, leading to systemic signs of liver failure ## Footnote These signs include ill-thrift and variable signs of hepatoencephalopathy.

Question 70

What syndrome affects Suffolk lambs in the USA and is characterized by worsening ataxia?

Answer 70

Neuroaxonal dystrophy ## Footnote It progresses to tetraparesis and is associated with accumulations of spheroids in the brain.

Question 71

What is a notable behavior of affected Romney lambs with neuroaxonal dystrophy?

Answer 71

They adopt a much crouched posture for a prolonged time before and after voiding urine ## Footnote This behavior may be due to extensor weakness and pelvic proprioceptive functional deficit.

Question 72

What is associated with equine neuroaxonal dystrophy?

Answer 72

An induced vitamin E-deficient state ## Footnote It may have a genetic basis

Question 73

What complicates the diagnosis of genetic diseases in Merino sheep?

Answer 73

Clinically and pathologically distinguishing genetic diseases from toxic, metabolic, and infectious disorders ## Footnote This results in progressive ataxia.

Question 74

What is a characteristic of Progressive Ataxia of Charolais Cattle?

Answer 74

Affected cattle show difficulty rising and dragging of toes, progressing to stiffness and ataxia ## Footnote Signs typically appear in cattle aged 6-24 months.

Question 75

What histologic lesions are classical in Progressive Ataxia of Charolais Cattle?

Answer 75

Demyelination and production of multifocal, acellular, pale eosinophilic plaques ## Footnote These are prominent in the cerebellar peduncles and medulla oblongata.

Question 76

What genetic mutation is associated with Progressive Ataxia of Charolais Cattle?

Answer 76

Single nucleotide polymorphism in the K1F1C gene ## Footnote This mutation leads to a functional knockout affecting myelin integrity.

Question 77

What syndrome affects Brown Swiss calves and is characterized by paraparesis and ataxia?

Answer 77

Bovine progressive degenerative myeloencephalopathy (Weaver syndrome) ## Footnote Signs usually appear at 5-8 months of age.

Question 78

What is a notable association with Weaver syndrome in Brown Swiss calves?

Answer 78

Positive association between the disease and milk production ## Footnote This highlights a possible link between genetics and productivity.

Question 79

What mutation is detected in Tyrolean gray calves related to degenerative axonopathy?

Answer 79

Mutation in the bovine MFN2 gene ## Footnote This disease is similar to Charcot-Marie-Tooth disease-2A2 in humans.

Question 80

What clinical signs are observed in Tyrolean gray calves affected by Demetz syndrome?

Answer 80

Progressive ataxia and paraparesis starting at 4-6 weeks of age ## Footnote Symptoms can lead to recumbency before one year of age.

Question 81

What histopathological changes are present in calves with citrullonemia?

Answer 81

Diffuse cerebrospinal edema is evident as fine, spongy neuropil, with astrocytic swelling and some neuronal degeneration

Question 82

What does the gene RELN code for?

Answer 82

Reelin (RELN) is suspected to play a critical role in neuronal migration and layer formation, and is suspected to be deleted in Churra sheep with lissencephaly and cerebellar hypoplasia

Question 83

What is the pathogenesis of daft lamb disease?

Answer 83

Likely inherited as an autosomal recessive trait, however environmental factors not totally excluded

Question 84

What histopathological changes are found in calves with congenital myoclonia?

Answer 84

Degrees of vacuolation of the brainstem and spinal cord (status spongiosus), prominent in white matter. Some have no consistent lesions.