Homocysteine disease (1)

Homocysteine disease (Cystinosis)

First, biochemical principle
Homocysteine disease is a lysosomal storage disease, due to cystathionine amine can not be carried through the lysosomal membrane, so the accumulation of homocysteine in the lysosomal caused a lot of organ dysfunction of cells, the kidneys are the most serious damage. Can be divided into three types: 1. Nephropathogenic type (or child-type); 2. Between type (or juvenile onset); 3. Benign type (or adult). One of nephropathy in type (child type) are the most common type.
Metabolic disorders --
Caused by the cysteine lysosomal storage in the kidneys, bone marrow, conjunctiva, thyroid, muscle, choroid plexus, brain mass, and lymph nodes of the main causes are still unknown, most of the enzymes break down homocysteine defect or not the conclusions of the study. However, and normal lysosomal cysteine of comparison can still be seen in the lysosomal cystine out of the ability of lysosomal markedly reduced. This anomaly may be responsible for carrying conveyor homocysteine through the lysosomal membrane protein atoms on the defect. Why is homocysteine storage will lead to loss of function of cells is still no reason to answer, but recent in vitro (in vitro) experiments pointed out that the proximal renal tubular cell storage will cause homocysteine three phosphoric acid adenosine (ATP) of缺乏.

Second, genetic mechanisms and genetic model
Degenerative kidney disease for homocysteine autosomal recessive genetic disease, juvenile and adult-type is the same genetic model.

Third, diagnostic methods
Homocysteine diagnosis can check the white blood cells to establish the concentration of free cysteine, the merger of homocysteine neuropathy patients white blood cells of normal homocysteine concentration is about 50 ~ 100 times. Combination of technical inspection of the use of protein polymorphonuclear white blood cells cystine concentrations are very sensitive, or even can detect homozygous gene varies from those with (heterozygous carriers). Such inspection techniques can also be used for fibrous tissue, conjunctiva organizations, and muscle and other cells, so in the first three months of pregnancy from skin, amniotic fluid cells or chorionic cultivated fibrous disease of the middle class to provide homocysteine pre-genetic diagnosis.

Four, clinical characterization of
Child care type cysteine deficiency

The first phase
After birth, usually at 3 to 6 months are asymptomatic, while in one-year-old will appear before the clinical symptoms. These symptoms include: anorexia, vomiting, polyuria, and not dependent. If you do not timely diagnosed, there is no vitamin D, at 18 months will be presented rickets. At the same time, if the urinary glucose and protein, that is, whether the patient is suspected to be suffering from disease homocysteine. When symptoms arise, usually in the first visit will be entirely performance Fanconi's syndrome (Franconi's syndrome) symptoms. Symptoms of this syndrome include: urine sugar normal blood sugar values (normoglycemic glycosuria), amino acids in urine (generalized aminoaciduria), there is β2-microglobulin protein and lysosome substantial tubular secretion of urine protein (tubular proteinuria), combined with low phosphate salt of phosphoric acid in urine hyperlipidemia (phosphaturia with hypophosphatemia), and due to substantial loss of potassium and sodium carbonate caused severe hypokalemia, hyponatremia, and acidosis. Often merging many high calcium in urine and blood urea is too small. Botulinum salty (Carnitine) loss resulting from renal tubular botulinum salty (Carnitine) insufficient, and at the same time can be seriously complicated by abnormal urine concentrated urine caused by many, every day from about 2 to 5 liters of urine. Homocysteine patients the typical profile of urine: white, turbidity of Special Taste, Taste This may be due to amino acids from urine.
Biological symptoms and proximal tubular reabsorption defect-related functions, which led to serious water and electrolyte imbalance, or even life-threatening. Fever often happened, the reason might be from dehydration. Will happen cases were smaller stones, stones and urine mainly to exclude excessive urate, calcium, and organic acids relevant. Suffering from disease homocysteine white children will show golden hair and tan skin is more difficult.
Cysteine deficiency violations of the most important parts are the eyes, photophobia are just beginning, usually 2 ~ 3 years old at the time there will be more or less the symptoms of photophobia, ophthalmology sub-beam and optical microscopy can be seen cystine crystals storage, while the merger retinopathy fundus abnormalities.

Stage renal failure (ESRF)
Symptoms of end stage renal failure are serious adverse renal growth Glomerular filtration rate decreased, while the kidney in 6 ~ 12 years old when renal failure. With cysteamine (cystiamine) treatment can delay the occurrence of renal failure, if that is born within one month after the beginning the effect of better treatment, but also help to improve growth rate. This kind of therapy in glomerular filtration rate of renal failure to reduce the process, may also increase the excretion of urine increased and Fanconi's syndrome improvement. Renal failure at the end of the period will be the development of serious renal hypertension, the patient may also be in hemodialysis, the phenomenon of recurring nosebleeds. After kidney transplant, even if the cystine crystals are deposited on the graft-on, you would not have Fanconi's syndrome, post-transplant patients are many symptoms of renal tubular function from exclusion.

Late symptoms
With renal replacement therapy and transplantation of organs other than the kidney was found to continue for storage homocysteine, so apart from violations of kidney cysteine know but also violations of the eyes, thyroid, liver, spleen, pancreas, muscles and central nervous system.
Advanced eye complications
The severity of eye complications varies from person to person, the cornea gradually sediment storage in all the patient's corneal stroma and iris stroma and the former crystal surface, in addition there is also some people retinal sediment storage. Photophobia, tears, and the eyelids may lead to varus visual impairment, these symptoms may be due to corneal erosion of the epidermal cells and eventually lead to keratopathy. Kidney transplant can be improved photophobia. Vision will gradually subside, some young eyes that happened symptoms sick even blindness.

Endocrine disorders
Low endocrine disorders including thyroid, pituitary gonadal function and insulin secretion disorders.
1. Low Thyroid Function: Thyroid function abnormalities are usually at the age of 8 ~ 12 happened, but some people even after the age of 20 will not be Low thyroid function, clinical presentation was not obvious at this time, so in a systematic examination of thyroid function, Low thyroid function may also be caused partly due to growth retardation.
2. Pituitary gonadal function: a cysteine in the male patients are often low plasma testosterone and high follicle-stimulating Fibroin / luteinising hormone (FSH / LH), they may be the development of secondary sexual characteristics have been hampered . Gonadal function of women appears to be normal.
3. Endocrine pancreas: Some cysteine deficiency in kidney transplant patients after the merger of high blood sugar after surgery and permanent insulin-dependent diabetes mellitus.