Mitochondrial Myopathies and Muscular Dystrophies Flashcards
What is the inheritance pattern of mitochondrial myopathies?
Mitochondrial (maternal) inheritance
What histological feature is characteristic of mitochondrial myopathies?
Ragged red fibers on muscle biopsy
Why do mitochondrial myopathies show maternal inheritance?
Mitochondria are inherited exclusively from the mother
What is the cause of mitochondrial myopathies at the cellular level?
Mutations in mitochondrial DNA (mtDNA) affecting oxidative phosphorylation
What is heteroplasmy in mitochondrial diseases?
The presence of both normal and mutated mtDNA within a cell, leading to variable expression of disease
What is the hallmark triad of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS)?
Stroke-like episodes, Lactic acidosis, Myopathy
What genetic mutation is associated with MELAS?
mtDNA mutations in tRNA genes (e.g., MT-TL1)
What metabolic abnormality is commonly seen in mitochondrial myopathies?
Lactic acidosis due to impaired oxidative phosphorylation
What are the key features of Myoclonic Epilepsy with Ragged Red Fibers (MERRF)?
Myoclonus, Seizures, Ataxia, Ragged red fibers on muscle biopsy
What mutation is associated with MERRF?
mtDNA mutation in MT-TK (tRNA-lysine gene)
What are the clinical features of Leber Hereditary Optic Neuropathy (LHON)?
Painless bilateral vision loss (optic atrophy), typically in young males
What mutation is associated with LHON?
mtDNA mutations affecting complex I of the electron transport chain
What is the primary affected organ system in mitochondrial myopathies?
Muscles (myopathy), Brain (encephalopathy), and sometimes eyes (optic neuropathy)
Why do mitochondrial myopathies cause exercise intolerance?
Impaired ATP production leads to muscle fatigue and weakness
What is the role of the electron transport chain in mitochondrial myopathies?
Defective oxidative phosphorylation leads to decreased ATP production and increased lactic acid
What is the treatment for mitochondrial myopathies?
Supportive care (exercise, vitamins, coenzyme Q10, L-arginine for stroke-like episodes in MELAS)
What is the inheritance pattern of mitochondrial DNA deletion syndromes like Kearns-Sayre syndrome?
Sporadic (not inherited maternally)
What are the key features of Kearns-Sayre syndrome?
Progressive external ophthalmoplegia, Pigmentary retinopathy, Heart block
What is a key difference between MELAS and MERRF?
MELAS presents with stroke-like episodes, whereas MERRF is characterized by myoclonus and seizures
What laboratory finding is common in mitochondrial myopathies?
Elevated serum lactate (due to defective oxidative phosphorylation)
What gene is mutated in Duchenne and Becker muscular dystrophy?
DMD gene (dystrophin)
What is the inheritance pattern of Duchenne and Becker muscular dystrophy?
X-linked recessive
What type of mutation causes Duchenne muscular dystrophy (DMD)?
Frameshift or nonsense mutation in the DMD gene
What is the key difference in mutation type between Duchenne and Becker muscular dystrophy?
Duchenne = frameshift/nonsense (nonfunctional dystrophin), Becker = in-frame mutation (partially functional dystrophin)
At what age does Duchenne muscular dystrophy typically present?
Early childhood (before age 5)
What is the hallmark clinical sign of Duchenne muscular dystrophy?
Gower sign (using hands to push up from the floor)
What muscles are first affected in Duchenne muscular dystrophy?
Proximal muscles, especially pelvic girdle
What serious complication is associated with Duchenne muscular dystrophy?
Dilated cardiomyopathy (leading cause of death)
What lab finding is elevated in Duchenne muscular dystrophy?
Creatine kinase (CK)
What muscle biopsy finding is characteristic of Duchenne muscular dystrophy?
Fibrofatty muscle replacement
What mutation causes Becker muscular dystrophy (BMD)?
In-frame mutation in DMD gene leading to partially functional dystrophin
How does Becker muscular dystrophy differ from Duchenne muscular dystrophy?
Milder symptoms, later onset (adolescence or early adulthood), slower progression
What is the typical age of onset for Becker muscular dystrophy?
Adolescence or early adulthood
What is the primary cause of death in Duchenne and Becker muscular dystrophy?
Dilated cardiomyopathy and respiratory failure
What genetic mutation causes myotonic dystrophy?
CTG trinucleotide repeat expansion in the DMPK gene (Type 1)
What is the inheritance pattern of myotonic dystrophy?
Autosomal dominant
What are the characteristic symptoms of myotonic dystrophy?
Myotonia (delayed muscle relaxation), Cataracts, Frontal balding, Testicular atrophy, Arrhythmias
What is the key clinical test for myotonia?
Hand grip myotonia (delayed relaxation after squeezing a hand)
What systemic features are associated with myotonic dystrophy?
Cardiac conduction defects, Insulin resistance, Cognitive impairment
What phenomenon explains worsening severity of myotonic dystrophy in successive generations?
Anticipation (expansion of CTG repeats in subsequent generations)
How does myotonic dystrophy differ from Duchenne and Becker muscular dystrophy?
It is autosomal dominant, involves myotonia, and has multisystem involvement
What treatment is available for muscular dystrophies?
Supportive care (physical therapy, steroids for Duchenne, cardiac monitoring)
What cardiac abnormality is common in myotonic dystrophy?
Conduction defects (risk of arrhythmias)
What facial feature is characteristic of myotonic dystrophy?
Hatchet face (due to muscle wasting)
