Cell Lecutres 4, 5, 6

Front 1

Myoclonic epilepsy with ragged red fibers (MERRF)

Back 1

* mitochondrial disease
* generalized muscle weakness, ataxia (loss of coordination), and multiple seizures. Complications are respiratory and cardiac failure.
* muscle biopsy shows aggregates of abnormal mitochondria, giving a ragged appearance to red muscle fibers.
* caused by a point mutation in a mitochondrial DNA gene encoding tRNA for lysine, resulting in deficiency in 2 complexes (I and IV) in the oxidative phosphorylation chain.
* muscles and neurons most affected due to dependence on oxidative phosphorylation.

Front 2

Leber’s Hereditary Optic Neuropathy (LHON)

Back 2

* mitochondrial disease
* Delayed bilateral loss of vision which could lead to total blindness due to degeneration of the optic nerve. Early signs are localized collection of distended blood capillary vessels around the start of the optic nerve which connects the eye balls to the cortex of the occipital lobes of the brain. With time there is a progressive optic atrophy and vision loss.
* LHON base changes affect a single codon in the gene for a protein in the electron transport pathway. The subsequent protein still works but not as efficient, resulting in lower ATP production.
* NADH dehydrogenase

Front 3

I-cell disease

Back 3

* Caused by a mutation in the GNPTA gene that leads to a deficiency in the enzyme UDP-N-acetylglucoseamine-1-phosphotransferase, enzyme catalyzing the first step in the tagging of lysosomal enzymes with mannose-6-phosphate in the golgi apparatus.
* A lysosomal storage disease, I-cell disease ("inclusion-cell disease"), is caused by a failure of the golgi apparatus to "tag" (by phosphorylation) all the hydrolytic enzymes that are supposed to be transported from the Golgi apparatus to the lysosomes. Lacking the mannose 6-phosphate (M6P) tag, the enzymes are directed to the plasma membrane, instead of the lysosomes, and secreted from the cell instead (exocytosis)---elevated lysosomal enzymes in the serum.
* Rare inherited metabolic disorder characterized by coarse facial features, skeletal abnormalities and mental retardation. The symptoms of I-cell disease are similar to but more severe than those of Hurler syndrome. The symptoms associated with this disorder typically become obvious during infancy and may include multiple abnormalities of the skull and face and growth delays.

Front 4

Tay-Sachs Disease

Back 4

* lysosomal storage disease
* caused by a genetic defect that prevents the formation of an essential enzyme that breaks down complex lipids called gangliosides. An accumulation of these lipids damages the nervous system, causes mental retardation, and death in early childhood.
* caused by a failure to produce an enzyme needed to break down sphingolipids (fatty acid derivatives found in all cell membranes).

Front 5

Gaucher's dissease

Back 5

* lysosomal storage disease
* caused by a failure to produce an enzyme needed to break down sphingolipids (fatty acid derivatives found in all cell membranes).

Front 6

Mucopolysaccharidosis I (MPS-I)

Back 6

* lysosomal storage disease
* Caused by a failure to synthesize an enzyme (α-L-iduronidase) needed to break down proteoglycans like heparan sulfate.

Front 7

X-linked adrenoleukodystrophy (X-ALD)

Back 7

* Peroxisome disorder
* This disorder results from a failure to metabolize fatty acids properly. One result is deterioration of the myelin sheaths of neurons. The disorder occurs in young boys because the gene is X-linked. An attempt to find an effective treatment was the subject of the 1992 film Lorenzo's Oil.

Front 8

Zellweger syndrome

Back 8

* peroxisome disorder
* result from failure to produce functional peroxisomes.
* This disorder results from the inheritance of two mutant genes for one of the receptors (PXR1) needed to import proteins into the peroxisome.

Front 9

Kartagener’s Syndrome

Back 9

* A rare chronic lung disease that occurs when cilia are unable to move.
* Frequently associated with bronchiectasis (permanent dilation of bronchi and bronchioles) and sterility in males.
* Also called Primary Ciliary Dyskinesia, and Immotile Cilia Syndrome, Afzelius’ syndrome, Kartagener’s triad, Zivert's syndrome, and Zivert-Kartagener triad.
* Some common symptoms:
chronic rhinitis, recurrent or chronic sinusitis, recurrent or chronic bronchitis, bronchiectasis, olfactory impairment, infertility

Front 10

Epidermolysis bullosa simplex (EBS)

Back 10

* Mutations of keratin genes result abnormal assembly of keratin filaments, weakening the mechanical strength of cells
* characterized by skin blisters after minor trauma (keratin 5 and 14 genes