Neurogenetcs

Question 1

Inborn Errors of Metabolism:

Answer 1

Metabolic disorders result from the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or
deficiency of a specific metabolite

Question 2

 Dual genome origins of mitochondrial disorders:

Answer 2

Nuclear DNA (nDNA)
 Mitochondrial DNA (mDNA)

Question 3

o Mitochondrial disorders are freq

Answer 3

Disorders of oxidative phosphorylation

Mutations in mitochondrial DNA disrupts mitochondrial function in the respiratory chain leading to multi-organ dysfunction
over time in people who may or may not have relatives with similar experience.

Question 4

only ___ transmt dseases

Answer 4

females

Question 5

male:female rato

Answer 5

1 (males can be affected!)

Question 6

Heteroplasmy

Answer 6

Wild-type and mutant mtDNA in cells, tissues
 Single mitochondria can harbor wild-type and mutant
mtDNA
 In normal subjects, all mtDNA’s are identical
(homoplasmy)

Question 7

o Mitotic segregation

Answer 7

Random distribution nl, mutant
 Explains tissue-related and age-related distribution of
clinical features

Question 8

o Threshold effect

Answer 8

 Minimal # of mutant mtDNA must be present before
oxidative dsyfunction occurs
 Lower threshold in tissues highly dependent on oxidative
metabolism
 Explains clinical signs that change—if and when the
pathogenic threshold is metclinical effects; age-related
and tissue-related differences.

Question 9

Mitochondrail encephalomyopath, lactic acidosis, stroke-like episodes (MELAS)

Answer 9

Point mutation 3243 in tRNA Leu gene

Question 10

o Myoclonic epilepsy myopathy with ragged red fibers (MERRF)

Answer 10

 Point mutation at nt8344 and/or 8356 in tRNA Leu

Question 11

o Neuropathy, ataxia, retinitis pigmentosa, seizures, dementia (NARP)

Answer 11

 Point mutation at 8993 in the ATPase 6 genes

Question 12

CSF & Urne

Serujm

Answer 12

Urine: amino acids, organic acids, carnitine
o CSF: amino acids, organic acids
Serum: amino acids, carnitine, lactate and pyruvate, Creatine Kinase

Question 13

tx

Answer 13

The “enhancement” of respiratory chain function:
 Oral supplements like coenzyme Q, carnitine, thiamine, succinate, folate, methylene blue
o Removal of “noxious” metabolites:
 E.g. lactate
o Scavanging of free radicals “leaking” from impaired respiratory chain function
o Symptomatic treatment
o Exercise
o Surgery (e.g., eyelid ptosis)
o Cochlear implants for deafness, hearing loss
o Heart transplants
o Genetic counseling

not veryhelpful