Lipid Deposition Myopathy
Introduction
Introduction to lipid deposition myopathy Lipid sedimentary myopathy (LSM) refers to abnormal deposition of lipids in muscle and is a major pathological change. The disease is a metabolic myopathy caused by defects in the oxidation process of long-chain fatty acids in the muscle, and is a manifestation of hereditary diseases of fat metabolism in the nervous system. The disease was first described by Engel et al in 1973. Domestic Cao Peizhi et al. (1990) first reported 2 cases, and various reports have been published since then. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: Cardiomyopathy Hypoglycemia
Cause
Causes of lipid deposition myopathy
Family history (30%):
Half of the patients have a family history, autosomal recessive inheritance, body fat metabolism is systemic, fat metabolism disorders can occur throughout the body, and become a family genetic disease, such as lipid deposition in brain tissue can cause brain lipids Sedimentosis, manifested as encephalopathy syndrome, this type of disease is mainly seen in infants and young children, often accompanied by heart, liver and other visceral damage.
Lipodystrophy (30%):
Lipid deposition myopathy is a manifestation of fat metabolism disorder involving skeletal muscle. Any obstacle in the process of biochemical transformation of fat metabolism can lead to accumulation of lipids in muscles or various organs of the body, causing the cause of LSM. Commonly known as carnitine deficiency or carnitine palmitoyltransferase deficiency.
Pathology (30%):
Lipids in muscle are a general term for fats and lipids and their derivatives. Fat is triacylglycerol. Lipids are substances similar in physical properties to fats, including phospholipids, glycolipids, sterols and sterol esters. The lipids are gradually hydrolyzed into free fatty acids and glycerol by tissue lipase for tissue utilization.
When the normal skeletal muscle is at rest and exercise, its energy is derived from the -oxidation of fatty acids in the mitochondria. The fatty acids in the body are divided into short chains (2~4C) and medium and long chains according to the number of C atoms contained. ~12C) and long chain (12C or above), carnitine is an important metabolic active substance in the human body, 98% is stored in the muscle, and the rest is found in the liver, kidney and extracellular fluid. Carnitine is present between the mitochondria and the outer membrane. It has two basic functions: first, transfer long-chain fatty acids through the mitochondrial inner membrane, into the matrix for -oxidation; secondly, by regulating mitochondrial coenzyme A (CoA) and fatty acyl-CoA (acyl-CoA) The ratio (CoA/acyl-CoA) prevents acyl-CoA from accumulating in the mitochondria, thereby maintaining membrane stability.
The oxidation process of long-chain fatty acids is a series of biochemical transformation processes. Under the catalysis of fatty acid and CoA on the outer membrane of CoA, a high-energy sulfatide bond, ie activated fatty acyl-CoA, is formed. It does not directly pass through the mitochondrial inner membrane, but must rely on the action of carnitine palmtoyl transferase (CPTI) located on the inner side of the mitochondrial outer membrane to convert fatty acyl-CoA and carnitine into fatty acylcarnitine ( After acyl-carnitine, it can enter the matrix through the mitochondrial inner membrane under the catalysis of carnitine acylcarnitine translocase (CT). After the fatty acylcarnitine enters the matrix, it must pass through the mitochondria. The action of carnitine palmitoyltransferase II (CPTII) on the inner side of the membrane converts the fatty acylcarnitine into fatty acyl-CoA and carnitine, the former undergoes -oxidation in the matrix, and the carnitine flows out again through the action of the enzyme. The mitochondrial inner membrane, in order to again pass the fatty acyl-CoA through the mitochondrial inner membrane in the same way, therefore, carnitine becomes a vehicle for the oxidation of long-chain fatty acids into the mitochondrial matrix, this cycle Cheng called carnitine ring (carnitine cycle).
75% of human carnitine is derived from food. It is rich in red meat and fish. It is slowly absorbed by intestinal epithelial cells and then enters the liver. Carnitine is excreted in the feces and urine, and some are reproduced in bile. The normal diet cannot be satisfied. The entire body needs, but must be endogenously synthesized, the raw materials are lysine and methyl lysine, and mainly synthesized in the liver.
The cause of LSM is mainly carnitine deficiency or carnitine palmitoyltransferase deficiency, but any obstacles in the biochemical conversion process of fat metabolism mentioned above can cause lipid accumulation in muscle or systemic organs.
Pathological features: more muscle biopsy specimens, frozen sections, observed by histochemical staining, whether it is carnitine deficiency, or carnitine palmitoyltransferase deficiency, can be found under light microscopy: HE and modified Gomori three staining It shows that there are a large number of circular vacuoles or defects in the sarcoplasm and under the sarcolemma. The oil red O staining is the lipid droplets. The ATPase staining indicates that the lipids are deposited most in the type I muscle fibers, followed by IIA. Type, again type IIB muscle fiber, the reason may be related to type I muscle fiber is more dependent on fat metabolism, patients with type I carnitine palmitoyltransferase deficiency, during the onset of myoglobinuria, visible muscle fiber necrosis, and type I Muscle fiber damage is heavier and can be followed by regeneration.
Electron microscopy showed that the diameter of the lipid droplets varied from less than 1 micron to several micrometers. The lipid droplets had no membrane and were distributed in parallel between the myofibrils or under the sarcolemma. However, different patients should be noted. The content variation is large, the number and size of mitochondria are increased, and the mites are not clear. Because muscle lipid and glucose metabolism are carried out in the mitochondria, in the muscle fibers of LSM patients, glycogen particles are sometimes seen to increase at the same time. Microscopically, PAS staining can be found, and abnormal mitochondria can be found under electron microscope, and even lattice-like inclusion bodies are displayed.
In addition, it should be noted that normal human muscle cells may contain a small amount of lipid droplets, and the morphometric study found that the content is less than 0.2% of the cell volume, so it is easier to distinguish.
Prevention
Lipid deposition myopathy prevention
Genetic counseling, prevention measures include avoidance of close relatives, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of children.
Complication
Lipid deposition myopathy complications Complications, cardiomyopathy, hypoglycemia
Myoglobinuria and renal failure may occur, such as carnitine deficiency, and systemic, may have cardiomyopathy, and often accompanied by systemic signs such as low ketone hypoglycemia.
Symptom
Symptoms of lipid deposition myopathy common symptoms symmetrical muscle weakness, muscle weakness, muscle weakness, proteinuria
LSM caused by carnitine deficiency is common in children, and adults can also develop disease. Most of them are slow onset, mainly involving skeletal muscles, symmetrical muscle weakness in limbs, severe involvement of limb muscles, and a small degree of muscle atrophy. In addition, the neck muscles, masticatory muscles, swallowing muscles and tongue muscles can be affected. The muscles move for a long time, the weakness is obviously aggravated and accompanied by muscle pain. As the disease progresses, the muscle weakness gradually increases. The general course of disease is several months to several years. .
If it is a disease caused by carnitine deficiency, and is systemic, in addition to the performance of the proximal extremity skeletal muscle weakness, but also cardiomyopathy, and often with systemic signs of low ketone hypoglycemia.
LSM caused by carnitine palmitoyltransferase deficiency, the most common type I CPT deficiency, is autosomal recessive, the gene is located in 1ql2, mostly in adolescence, male incidence is higher than female, type I CPT deficiency The clinical features of myalgia, muscle weakness, tendon, long-lasting exercise and long-term fasting can cause muscle stiffness and paroxysmal myoglobinuria. About one-fourth of patients cause renal failure, and women generally have milder symptoms.
The diagnosis of lipid deposition myopathy is mainly based on the majority of patients with adolescent disease, the disease progresses slowly, with the proximal symmetry weakness of the extremities, but also the face, chewing and swallowing muscles, myoelectricity is myogenic damage The serum CK test, most significantly increased, enzymatic histochemical staining of the muscle biopsy tissue (HE and ATPase staining), a large number of vacuoles in the type I muscle fibers, oil red O staining positive; electron microscopic observation of myogenic A large amount of lipid droplets between the fibers can be diagnosed.
Examine
Examination of lipid deposition myopathy
Serum creatine phosphokinase (CK) was significantly elevated, and other muscle enzymes such as lactate dehydrogenase were also significantly elevated. In patients with type I CPT deficiency, serum CK increased simultaneously during myoglobinuria.
Electromyography showed mostly myogenic damage.
Diagnosis
Diagnosis and differentiation of lipid deposition myopathy
If the disease is caused by carnitine deficiency or carnitine palmitoyltransferase deficiency, or due to other enzyme defects, biochemical detection of the patient's muscles must be made clear.
Because this disease and glycogen storage disease and mitochondrial myopathy are both metabolic myopathy, and its clinical manifestations are proximal limb weakness, muscle biopsy in this disease, although a large number of lipid deposition in the muscle fiber, but also Occasionally, a small amount of muscle fibers contain more glycogen and abnormal mitochondria, so attention should be paid to identification.
In addition, the disease should be differentiated from multiple myositis, muscular dystrophy, spinal muscular atrophy and myasthenia gravis.
