Mitochondrial Disorders Flashcards Preview

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Flashcards in Mitochondrial Disorders Deck (19):
1

Barth syndrome

X-linked
cardiomyopathy, skeletal myopathy, cyclic neutropenia
gene: tafazzin

2

Kearns-Sayre syndrome

caused by large mtDNA deletion especially 5kb "common" deletion; also A3243G and nuclear genes
symptoms: chronic progressive external ophthalmoplegia (weakness of eye muscles), proximal muscle weakness, onset 100mg/dL, dementia (some)

3

Leigh disease

cranial nerve abnormalities, respiratory dysfunction and ataxia
progressive and lethal
Many etiologies including complex 1 deficiency, complex 4 deficiency, mtDNA T8993G/C, and PDHC deficiency

4

Lebers Hereditary Optic Neuropathy
(LHON)

rapid central vision loss in adolesence/young adults; may also have dystonia
usually caused by homoplasmic mtDNA mutations most commonly G11778A, G3460A, T14484C
low penetrance; blindenss in males 3-4x more likely than females

5

MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes
Onset 5-15 years
Most commonly heteroplasmy for A324G however variety of other genetic etiologies possible
RRF and abnormal ETC activity frequently absent

6

MERRF

Myocolonic epilepsy and ragged red fibers
Mulitple symmetrical lipomatosis around neck (some patients)
most commonly heteroplasmy of A8344G

7

MNGIE

Mitochondrial myopathy, peripheral neuropathy, GI and encephalopathy
GL disease includes diarrhea and pseudoobstruction
adult onset; multiple mtDNA mutations or secondary to auto recessive mutations in thymidine phosphorylase gene

8

mtDNA depletion syndrome

Infantile onset; AR mutations in nuclear encoded genes involved in mtDNA replication or maintenance
myopathy form caused by TK2 mutations; hepatic form caused by dGK mutations
Diagnosis caused by muscle biopsy comparison of mtDNA:nDNA ratio

9

NARP

Neuropathy, ataxia, retinitis pigmentosa
caused by moderate heteroplasmy for T8993G/C (high heteroplasmy causes Leigh syn)

10

Pearson syndrome

Infantile refractory sideroblastic anemia (with variable other blood cell anomalies) and other exocrine pancreatic dysfunction
caused by large mtDNA del/dups
KSS can occur in survivors

11

A1555G

Aminoglycoside-associated deafness, non-syndromic deafness, maternally inherited cardiomyopathy

12

A3243G

MELAS
Also variety of neuromuscular, endocrine, renal disease
Common phenotypes: migranes, diabetes, deafness

13

What percentage of diabetes is likely caused by A3243G mutation?

1 percent

14

A8344G

MERRF

15

T8993G/C

Moderate levels of heteroplasmy cause NARP, higher levels cause Leigh disease

16

12S rRNA gene mutations

amniglycoside and "sporadic" hearing loss

17

tRNA leucine gene UUR

mutational hotspot; includes mutations for that cause MELAS or myopathy/cardiomyopathy

18

tRNA isoleucine gene

mutations here cause cardiomyopathy

19

Cytochrome B gene

sporadically mutated in some patients with isolated cardiomyopathy