Mitochondrial Myopathies Flashcards
A 25-year-old woman presents with progressive muscle weakness, difficulty moving her eyes, and frequent episodes of severe fatigue. She reports a family history of similar symptoms in her mother and maternal uncle. Laboratory studies reveal elevated serum lactate levels both at rest and after exercise. A muscle biopsy shows ragged red fibers. Which of the following is the most likely underlying cause of her condition?
A) Autosomal dominant mutation in nuclear DNA
B) Deletion in mitochondrial DNA inherited from her father
C) Mutation in mitochondrial DNA with maternal inheritance
D) X-linked mutation affecting oxidative phosphorylation
E) Point mutation in nuclear DNA encoding creatine kinase
Answer: Mutation in mitochondrial DNA with maternal inheritance
Explanation: Mitochondrial Myopathies are a group of disorders caused by mutations in mitochondrial DNA, which are exclusively inherited from the mother. These mutations impair oxidative phosphorylation, leading to decreased ATP production and symptoms affecting high-energy-requiring tissues, such as muscles and the brain. Clinical findings include ophthalmoplegia, ptosis, and muscle weakness. Laboratory studies often show elevated lactate levels, and muscle biopsy reveals ragged red fibers, a hallmark of mitochondrial myopathies.
Incorrect Answers:
A) Autosomal dominant mutations in nuclear DNA do not typically cause mitochondrial myopathies.
B) Mitochondrial DNA is maternally inherited; paternal inheritance of mitochondrial mutations does not occur.
D) X-linked mutations are not involved in mitochondrial myopathies, as mitochondria are inherited maternally.
E) Point mutations in nuclear DNA encoding creatine kinase would not explain ragged red fibers or elevated lactate.
What is the inheritance pattern of Mitochondrial Myopathies?
Maternally inherited (mitochondrial DNA mutations)
What is the primary pathophysiology of Mitochondrial Myopathies?
Impaired oxidative phosphorylation, leading to decreased ATP production and increased lactic acid and pyruvate accumulation. Tissues with high energy requirements
are preferentially affected (eg, CNS, skeletal muscle).
What are common clinical features of Mitochondrial Myopathies?
Ophthalmoplegia, ptosis, exertional muscle weakness, and systemic symptoms affecting high-energy organs (e.g., brain, heart, retina)
What are the characteristic findings on muscle biopsy in Mitochondrial Myopathies?
Ragged red fibers due to subsarcolemmal accumulation of abnormal mitochondria
What laboratory findings are associated with Mitochondrial Myopathies?
Elevated lactate and alanine levels in serum, urine, or cerebrospinal fluid (CSF); normal creatine kinase (CK) levels
What are the major subtypes of Mitochondrial Myopathies?
MELAS, MERRF, CPEO, Kearns-Sayre syndrome, LHON, and Leigh syndrome
What are the clinical features of MELAS syndrome?
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, along with muscle weakness and seizures
What mutation is commonly associated with MERRF syndrome?
Point mutation of the 8344th base pair in mitochondrial DNA
“myoclonic epilepsy with ragged red fibers”
- Generalized seizures
- Cerebellar ataxia
- Dementia
In MERF, why are there “ragged” red fibers?
Light microscopy with stain will show ragged red fibers due to compensatory proliferation of mitochondria.
Electron microscopy will show mitochondrial crystalline inclusions.
What mitochondrial myopathy is associated with progressive ophthalmologic disorder characterized by the inability to move the eyebrows and eyes?
Chronic progressive external ophthalmoplegia.
-bilateral ptosis.
Ophthalmoplegia, retinitis pigmentosa, and AV blocks are associated with which mitochondrial myopathy?
Kearns-Sayre syndrome
Which mitochondrial myopathy is associated with subacute visual changes in one or both eyes, usually in young adults. Funduscopic exam typically shows circumpapillary telangectasia?
Leber hereditary optic neuropathy (LHON)
What part of the electron transport chain is impaired with LHON?
mutations occur in complex I of the ETC.
LHON occurs more in males or females?
males
