Myoclonic Epilepsy

Part B is associated with Topic 3 and its investigation. This question assesses module learning outcomes CS2, CS3, KS2 and KS4.
Rare diseases are often grouped by the organelles they affect, or by their symptoms. One such grouping is the ‘myopathies’, which collects together several rare diseases that have muscle weakness as one of their symptoms. Using the skills you developed in Activity 1.2, use the NLM database to research the two different myopathies listed below to answer questions (a)–(c).
• Myoclonic epilepsy with ragged-red fibers (MERRF)
• Neutral lipid storage disease with myopathy (NLSDM)

Myoclonic epilepsy with ragged-red fibers (MERRF)

Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family.
MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells are called ragged-red fibers. Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). People with this condition may also develop hearing loss or optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy. Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin. MERRF is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.In most cases, people with MERRF inherit an altered mitochondrial gene from their mother, who may or may not show symptoms of the disorder. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MERRF.
Neutral lipid storage disease with myopathy (NLSDM)
Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. People with this condition have muscle weakness (myopathy) due to the accumulation of fats in muscle tissue. Other features of this condition may include a fatty liver, a weakened and enlarged heart (cardiomyopathy) inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), and type 2 diabetes (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

• a. Describe what is known about the inheritance pattern and name the gene/s that is/are mutated in each of these myopathies.
(4 marks)
• b .Both of these myopathies show an underlying reduction in cellular energy levels. Based on the information in the NLM database and your knowledge from S290, briefly describe in your own words how the underlying genetic mutations in both diseases lead to deficits in cellular energy levels. Your answer should clearly indicate which cellular energy source(s) and which stage of ATP production are affected.
(4 marks)
• c .What causes the muscle weakness in each of these myopathies?
(2 marks)