Neurogenetic Disorders

Question 1

Friedreich’s Ataxia

Answer 1

• Autosomal-recessive
• Trinucleotide repeat disorder (GAA) in gene the encodes FRATAXIN –> leads to impairment in mitochondrial functioning
• impairment in both sensory and cerebellar function

Sx:

• Staggering gait
• Frequent falling
• Other features: dysarthria, scoliosis, dimished or absent reflexes, cardiomyopathy, deafness, oculomotor abnormalities

Question 2

Neurofibromatosis Type 1 (von Recklinghausen’s disease)

Answer 2

• Autosomal dominant neurocutaneous disorder (100% penetrant, but with variable expression)
• Caused by mutations in neurofibromin gene (on chromosome 17), a tumor suppressor gene

Findings:

• cafe-au-lait spots
• Lisch nodules: pigmented iris hamartomas
• Neurofibromas in skin
• optic gliomas
• Pheochromocytomas

Question 3

Adrenoleukodystrophy

Answer 3

• Rare, genetic disorder characterized by the breakdown or loss of the myelin sheath surrounding nerve cells in the brain
• X linked recessive (males predom affected)
• Accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex because the fatty acids are not broken down by an enzyme in the normal manner
• Results in progressive dysfunction of the adrenal gland
• symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance

Question 4

Maple Syrup Urine Disease

Answer 4

• neurometabolic disorder
• Due to deficiency in branched chain keto-acid dehydrogenase, resuling in increased branched chain amino acids (leucine, isoleucine & valine)
• Well at birth, w/ poor feeding around 3-4 days
• Urine smells like maple syrup due to (+) urine ketones

If untreated, can lead to:

• brain swelling & Seizures
• Herniation
• Coma
• Death

Question 5

Urea Cycle Disorders (Hyperammonemia)

Answer 5

• Neurometabolic disorder
• Due to defect in breakdown of ammonia, resulting in elevated ammonia + metabolic alkalosis
• All AR, except OTC (X-linked)
• Neonate well for first 24-48 hours, then develops:
  
  • Lethargy, vomiting, hyperventilation, hypothermia
  • May appear septic

Question 6

Tyrosine Hydroxylase Deficiency

Answer 6

• Neurotransmitter disorder
• Autosomal recessive
• Symptoms include: oculogyric crises (crossed-eyes), parkinsonian symptoms, tremor, hypokinesia, truncal hypotonia, irritability, and alterations in tone with hypotonia on one end of the spectrum to spasticity at the other extreme
• Diagnosis: CSF Neurotransmitter studies

Question 7

Aicardi syndrome

Answer 7

• Brain malformation disorder

Clinical Triad

1. Partial or complete agenesis of the corpus callosum
2. Infantile spasms
3. Ocular abnormality called lacunae of the retina of the eye resulting from retinal dysplasia, and ocular coloboma

• Typically diagnosed between 3-5 mo
• Affects only females
• X-linked

Question 8

Huntington Disease

Answer 8

• Genetic dementia (decline in cognitive function)
• Polyglutamine Triplet repeat disease:
  CAG repeat in coding region of Huntingtin
• AD late onset neurodegenerative disorder
• Cognitive impairment, chorea, depression and other psychiatric symptoms
• Death 15-20 years after onset

Juvenile Onset Type

• Rigidity
• Bradykinesia
• Epilepsy
• Accelerated Disease course

Question 9

Rett Syndrome

Answer 9

• X linked neurodegenerative disorder; Mainly females; Mainly sporadic
• Due to mutations or deletions in MECP2 gene which controls gene expression
• Onset of symptoms around 18 months of age

Symptoms include:

• Head growth deceleration
• Language skills disappear
• Stereotypes replace purposeful hand use
• Autistic features
• Gait ataxia
• Seizures, abnormal breathing
• Kyphosis/scoliosis