Mucolipidosis type IV (ML IV, ganglioside sialidase deficiency, or ML4) is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation channel, mucolipin1. These mutations disrupt cellular functions and lead to a neurodevelopmental disorder through an unknown mechanism. Researchers dispute the physiological role of the protein product and which ion it transports. Signs and symptoms
Most patients with ML IV show psychomotor retardation (i.e., delayed development of movement and coordination), corneal opacity, retinal degeneration and other ophthalmological abnormalities. Other symptoms include agenesis of the corpus callosum, iron deficiency resulting from an absence of acid secretion in the stomach, achlorhydria. Achlorhydria in these patients results in an increase in blood gastrin levels. These symptoms typically manifest early in life (within the first year). After disease onset there occurs a period of stability, typically lasting two to three decades during which very little disease progression occurs. Pathophysiology
Mucolipin1 is thought to be localized in endosomes. An important property of mucolipin1 is that decreasing pH (acidification) results in deactivation of the protein, likely through an assembly defect. There are at least 29 known mutations in MCOLN1, located throughout the gene. Many of the known mutations result in no expression of mucolipin1. Milder mutations, such as ΔF408 and V446L, produce a dysfunctioning form of the cation channel.
Neither model is accepted as more than an approximation. Analysis of postural sway shows much more variation than is seen in a physical pendulum or even a pair of coupled pendulums. Furthermore, quiet standing involves activity in all joints, not just the ankles or hips.In the past the variation was attributed to random effects. A more recent interpretation is that sway has a fractal structure. A fractal pattern consists of a motif repeated at varying levels of magnification. The levels are related by a ratio called the fractal dimension. It is believed that the fractal pattern offers a range of fine and gross control tuning. Fractal dimension is altered in some motor dysfunctions. In other words, the body cannot compensate well enough for imbalances. Pathology
Although standing per se is not dangerous, there are pathologies associated with it. One short term condition is orthostatic hypotension, and long term conditions are sore feet, stiff legs and low back pain. Orthostatic hypotension
Orthostatic hypotension is characterized by an unusually low blood pressure when the patient is standing up. It can cause dizziness, lightheadedness, headache, blurred or dimmed vision and fainting, because the brain does not get sufficient blood supply. This, in turn, is caused by gravity, pulling the blood into the lower part of the body. Normally, the body compensates, but in the presence of other factors, e.g. hypovolemia, diseases and medications, this response may not be sufficient. There are medications to treat hypotension. In addition, there are many lifestyle advices.