Lip fold increase deformity

Introduction Patients with vascular keratoma syndrome have edema on the face, thickening of the lips, and increased deformity of the lips and folds. Fabry disease, vascular keratomas syndrome or Andeson-Fabry disease, or alpha-galactosidase A deficiency, is a multi- Organ multi-system diseases, including skin lesions, neurological diseases, such as non-perspiration, acromegaly, cardiovascular disease, ocular lesions, other such as anemia, lymphoid hyperplasia, hepatosplenomegaly, aseptic necrosis of the bone, Myopathy and hypogammaglobulinemia.

Cause

(1) Causes of the disease

The disease is a sexually linked dominant genetic disease, and the disease-causing gene is located in the middle segment Xq21 to Xq24 of the X chromosome. Therefore, hemizygous males are seriously ill, while heterozygous females have various conditions, most of which are mild (such as corneal ring-like turbidity), even asymptomatic, and a few are as heavy as males. This gene mutation leads to the deficiency of -galactosidase A (a lysosomal hydrolase), which prevents the terminal -galactose residue from dissociating from the neutral glycosphingolipid molecule, thus making such a medium Saccharo- sphingolipids, mainly ceramide trihexoside, also have fewer sphingosine trihexosides deposited in various organs of the body. It is clinically found that patients with Fabry disease of type B or AB often have early onset and severe illness, because these two blood groups also have two other glycosphingolipids, B and B1 glycosphingolipids, when -galactosidase When A is deficient, they are also unable to dissociate the alpha-galactose residue at the molecular end, and the B and B1 glycosphingolipids are also deposited together into organ tissues. Because patients with B or AB blood type have more glycosphingolipid deposition than patients with O or A blood type, they are seriously ill.

(two) pathogenesis

In 1967, Brady et al. clarified the biochemical defects of the disease. They believe that deficiencies in the lysosomal enzyme ceramide hexosyl triglucosidase activity result in a decrease in the catabolism of neuraminidase, leading to the deposition of intracellular neuroglycosyl galosyl sphingosine. The a-terminal end of the intracellular deposit is linked to a galactoside residue. Because of this understanding of this specific enzyme deficiency, it is now possible to accurately diagnose hemizygous males and to identify heterozygous female carriers and fetuses affected in the uterus.

It is now clear that vascular keratoma syndrome is an X-linked genetic disease with a defective gene located on the long arm of the X chromosome. The penetrance of this gene is high in hemizygotes, and the clinical manifestations of enzyme deficiency are both intra-family and inter-family. The entire genomic sequence of -galactosidase has been deciphered and a sufficient length of cD-NA can be obtained. Different families have different molecular arrangements, and there are exon mutations, gene rearrangements, and base pair deletions. Affected hemizygous males exhibit multi-system clinical manifestations, and heterozygous females have different clinical manifestations and are asymptomatic, but evidence of lipid storage can be found.

an examination

Related inspection

Maxillofacial examination

1. Kidney performance

Kidney involvement is mainly characterized by hypertension, hematuria, proteinuria and fatty urine, and edema occurs in 50% of patients. Barrier dysfunction such as concentrated dilution, acidification and other obstacles are early manifestations of the disease. As the disease progresses, 30% of patients develop renal failure at the end of the 20-40 age period, at which time the kidney volume becomes smaller. Renal vascular disease, such as severe glomerular lesions, can be complicated by renal infarction. Renal lesions are the leading cause of Fabry disease incidence and death. Cardiovascular disease and cerebrovascular disease are also common manifestations of this disease. Renal lesions are most often characterized by occult light proteinuria (0.5 to 2.0 g/24 h) between the ages of 20 and 30. 30 to 50 years old often develop to uremia with hypertension, and some patients develop early to 10 to 20 years old to end-stage renal disease.

Proteinuria in the general nephropathy range is not common. In patients without proteinuria, a Maltese cross in the urine or an oval-shaped liposome under a bright-field microscope was observed under a polarizing microscope, suggesting the possibility of a lipid storage disease. For example, the discovery of myelin in the urine can confirm Fabry disease. Heterozygous (female) and hemizygous (male) patients have 20 to 80 times more sphingolipids than normal people. The patient may have mild microscopic hematuria. Hemizygous renal failure is common because the disease is transmitted in a X-linked recessive manner. Heterozygotes can also progress to end-stage kidney disease.

2. System performance

(1) Skin vascular keratinoma: It is a characteristic lesion of this disease, the incidence rate is about 90%, and the average age of onset is 17 years old. The scrotal keratomas are most obvious, often accompanied by facial telangiectasia. In the super-surface layer of the skin, there are clusters of red, purple or red-black venous vasodilatation in the form of spots, which have a tendency to hemorrhage. Fading, a large rash can have excessive keratinization. The endothelial cells of the skin blood vessels and the smooth muscle are weakened by the deposition of glycosphingolipids and then expanded. It can only be seen at birth, and can be expanded to 4mm in the future. It can be raised above the surface and distributed in the so-called "sitting bath area" between the umbilicus and the knee (the lower part of the trunk, the arms, the hips, the hips and the perineum). With the increase of age, the number and area of keratinoma also increased.

(2) autonomic nervous system dysfunction: the nervous system manifestations are often the earliest symptoms of this disease, the age of onset is 10 years old, the initial performance can occur in children only 5 years old, can appear before vascular keratinoma many years ago, so It is necessary for pediatricians to understand this phenomenon.

The manifestations of neurological damage in vascular keratomas are mainly paroxysmal palmar pain (Fabrys crisis) and limb ant crawling. In patients with Fabrys disease, the typical manifestations of palm pain and limb ant crawling are after the hot and cold, exercise, and labor, intermittent tingling and burning pain in the palms and soles of the feet, radiating to the proximal extremities, and severe periodic episodes last for several minutes. In a few weeks. The rate of patients with periodic episodes was 77%, those with chronic disease were 89%, and those with lifetime duration were 90%. Can also be expressed as Raynaud's sign, abdominal pain. The number of pain episodes decreases with age and the degree is reduced. Predisposing factors include fever, warming, exercise, stress, and drinking. When the degree of pain is severe, it is often accompanied by fatigue, weakness, fever, sweating and increased blood sedimentation and mistaken rheumatism. Check the body without signs of the nervous system.

In addition, 37% of patients have symptoms of central nervous system damage, the age of onset is generally greater than 26 years old, manifested as stroke (24%), dementia, passive and depressed social interaction disorder (18%). Cerebrospinal fluid examination is normal, and magnetic resonance imaging (MRI) of the brain can detect early lesions of white matter and gray matter.

Impaired autonomic function can occur with less sweat or no sweat, shrinking, tear and sputum reduction, impotence and orthostatic hypotension, etc., about 69% of patients with gastrointestinal symptoms, manifested as postprandial abdominal pain, Diarrhea, nausea and vomiting, fat intolerance, etc., most patients are significantly thin.

(3) Eye lesions: Eye signs are one of the characteristic changes of Fabrys disease. Corneal opacity can be seen in all heterozygotes and most hemizygotes. Patients may present with abnormalities in the anterior and posterior lens, cataract and retinal vascular tortuosity, dilatation, corneal opacity, and corneal vortex deposits, although this does not affect visual or visual loss, especially in women 70% to 80% % can only show the eye signs of the disease. When the ophthalmologist finds that the patient has corneal degeneration or changes in the lens, Fabrys disease should be thought of, and the patient is recommended to do a genetic test to find out if other family members of the patient also suffer from it. The disease. Therefore, ophthalmologists should play a very important role in the diagnosis of Fabrys disease.

(4) Heart damage: Heart damage is often one of the causes of death in patients with Fabrys disease. Mainly manifested as conduction disorders, cardiomyopathy, coronary insufficiency or coronary artery occlusion leading to myocardial infarction, hypertension (increased renin secretion due to renal ischemia), valve and ascending aorta degenerative disease (mitral valve prolapse more common ). In general, the lysosomal enzyme -galactosidase A enzyme activity of Fabrys disease patients is only 1% to 17% of normal people. If the residual enzyme activity is high, the patient may be asymptomatic or only have cardiac lesions. When causing ischemic heart disease, patients may die of angina pectoris, myocardial infarction, and congestive heart failure.

(5) Other systemic organs: In addition to the above clinical manifestations, patients with vascular keratoma syndrome can also experience progressive sensorineural hearing loss (78%); edema on the face, thickening of the lips, increased deformity of the lips and folds (56) In addition, some patients may have hemolytic anemia, lymphadenopathy, hepatosplenomegaly, aseptic necrosis of the bone, myopathy, pulmonary dysfunction, low immune function, increased platelet aggregation and prone to thrombosis and embolism.

Although the disease has many characteristic manifestations, it is not uncommon for patients to be misdiagnosed for more than 10 years. In general, the age of onset of Fabrys disease patients is in late childhood or early adolescence, males are ill, females are carriers or mild patients, and type B and type AB blood types are early and severe. The average survival age of the patients was 50 years, and the female gene carriers had a longer survival age, about 70 years old. The cause of death is mainly renal failure or cardiovascular and cerebrovascular complications.

Due to the lack of function or activity of the lysosomal enzyme -galactosidase A required for the normal catabolism of ceramide trihexosides in patients with Fabry disease, there is a disorder in the metabolism of glycosphingolipids, resulting in nerves during lipid catabolism. Sphingolipids, mainly ceramide trihexoside (CTH), are widely deposited in various tissues of the body, such as vascular endothelium and smooth muscle intracellular, central nervous system neurons, peripheral nervous system ganglia, skin, eyes, Gastrointestinal tract, heart, kidney, etc., so the clinical symptoms are multi-system damage, sometimes based on a certain systemic symptoms. It is usually not difficult to make a clear diagnosis based on clinical manifestations, characteristic signs, and positive family history, biopsy tissue, and low activity of -galactosidase in cultured skin fibroblasts.

If the clinical presentation suggests an alpha-galactosidase A deficiency, the diagnosis can be aided by measuring the concentration of the enzyme in leukocytes isolated from peripheral blood. Hemizygous patients have almost no enzyme activity. If the activity of the enzyme reaches 6% to 20% of normal people, there may be no clinical symptoms. In heterozygotes, the level of activity of the enzyme is between normal and hemizygous. Determination of alpha-galactosidase A activity in leukocytes is not a sensitive method for identifying carriers, and it is preferred to determine the concentration of ceramide galactosidase and trihydroxylate in the urine. Prenatal diagnosis can be performed by measuring the level of -galactosidase A in cultured amniocytes.

Only a few storage diseases have the same renal lesions and distribution of reservoirs as Fabry disease. The formation of vacuolar cells in glomerular tubule epithelial cells is non-specific, but the ultrastructural features of inclusion bodies are diagnostic. In male patients with this disease and symptoms, such as inclusion bodies are widely distributed and the number of inclusion bodies in the affected cells is large, especially in epithelial cells of glomeruli, the diagnosis of this disease should be considered. Urine sediments found intact cells containing typical inclusion bodies and free myelin bodies, which are of great value for diagnosis.

Differential diagnosis

In the early stages of the disease or when the symptoms are not typical, it should be differentiated from the following diseases:

1. Rheumatism: Rheumatic fever is more common in clinical practice. It generally has a history of early streptococcal infection, anti-"O" increase, subcutaneous nodules, arthritis and chorea and other symptoms and signs, anti-rheumatic treatment is effective.

2. Drug-induced eye damage: drug-induced eye damage has a clear history of medication, such as chloroquine can cause corneal opacity similar to Fabrys disease.

3. Cardiovascular and cerebrovascular diseases: young people with severe painful neuropathy or convulsions, hemiplegia, personality and behavioral changes, with progressive renal, cardiovascular and cerebrovascular dysfunction, should be thought of this disease, MRI can be early Found brain damage.

In addition, attention should be paid to the differentiation of diseases of glomerulonephritis and renal tubular dysfunction caused by other causes.

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