What causes severe pseudohypertrophic malnutrition?

Severe pseudohypertrophic dystrophy is caused by a mutation in the gene encoding dystrophin on chromosome Hp21. It is an X-linked recessive genetic disease that usually affects males and females carry the mutated gene. However, in reality, only 2/3 of the patients' diseased genes come from their mothers, and the other 1/3 of the patients have their own dystrophin gene mutations. The mothers of these children do not carry the mutated gene and are not related to the onset of the children.

Dystrophin is located in the lipids of the muscle cell membrane and plays an important role in stabilizing the cell membrane and preventing cell necrosis and autolysis. Quantitative analysis shows that the dystrophin in the muscle cells of DMD patients is almost completely restored, so the clinical symptoms are aggravated, while BMD is only partially reduced, and the prognosis is relatively good. Since this protein is also partially present in the myocardium and the peripheral nerve structures of brain cell nuclei, some patients may have combined myocardial lesions, mental retardation or peripheral nerve conduction function detection disorders.

Microscopically, extensive degeneration and necrosis of muscle fibers of varying severity were observed, with occasional dark-stained muscle fibers. Intrafascicular fibrosis or fat filling was observed, and focal mononuclear cell infiltration was observed in response to necrotic muscle fibers.

Severe pseudohypertrophic malnutrition is almost only seen in boys. If the mother is a gene carrier, 50% of male offspring will develop the disease, usually starting at 2-8 years old. Initially, they feel clumsy in walking, prone to falling, unable to run or climb stairs. When standing, the spinal cord is lordotic, the abdomen is protruding, the two feet are apart, and the walking is slow and swaying, with a special "duck step" gait. It is very difficult to stand up from lying on the back, and one must first turn over and lie on the stomach, then climb the two knees with both hands and gradually support themselves upwards. It can also be seen in the proximal muscles of the limbs, quadriceps and arm muscles.

The children have normal motor development at birth or in early infancy, with a few having mild motor delay or unstable gait after walking independently, prone to falling. Symptoms generally become obvious after the age of 5, with increasingly severe weakness of the hip girdle muscles, a swaying duck-like gait, more frequent falls, inability to climb stairs and jump, and progressive reduction of shoulder girdle and systemic spinal strength.

Most people lose the ability to walk independently after the age of 10, and most develop weakness of the throat and respiratory muscles before the age of 20, a low voice, difficulty swallowing and breathing, and are prone to secondary infections such as aspiration pneumonia and death. BMD symptoms are milder, and the patient may survive to around 40 years old.