Homocysteine disease(2)

Etiology:

Homocysteine as a disease lysosomal storage disease, because of section 17 of the short arm of chromosome 13 position (17p13) of the CTNS gene defects, leading to cysteine (cystine) to carry out the lysosomal enzyme transport (transporter ) dysfunction, making the accumulation of homocysteine in cell lysosomal up, resulting in organizations and organs of the lesion.

According to time of onset and disease severity can be divided into three types: First, nephropathy type / child type (Nephropathic cystinosis); II, intermediate / juvenile (Intermediate cystinosis); three, non-nephropathogenic type / Adult (Non -nephropathic cystinosis). One of nephropathy in type / child-type the most common symptoms are the most serious.


Incidence:

The incidence of this disease is estimated at 1/200000. In the Brittany area of France (Brittany), found in the area of disease incidence of 1 / 26000.

At present, this disease has been classified as rare diseases Notice our country, it was estimated the incidence of the Taiwan area should be one ten thousandth of the following.

Genetic model:

For autosomal recessive genetic diseases, said parents with a mutation for the gene, the next generation of each child regardless of gender will have 1 / 4 chance of suffering from this disease.



Characterization of clinical on:

Typing clinical
Nephropathy type / child care-type patients in the newborn during the first few months are usually asymptomatic, but 6-9 when the month that is gradually emerging in anorexia, vomiting, polyuria, growth retardation of the situation, and a lesion of the kidney and other organs. Kidneys are the main clinical manifestations of Fanconi's syndrome.
Fanconi's syndrome (Renal tubular Fanconi syndrome):
Often in large happened in June, can not be due to renal tubular water, electrolytes, bicarbonate, phosphate, calcium, carnitine, glucose and amino acid molecules, such as re-absorption, and the emergence of polyuria, polydipsia, dehydration and even symptoms of acidosis.

Electrolyte and amino acid molecules, such as the loss will be patients with a variety of diseases; include: (1) low phosphate rickets; often cause pain when walking patients. (2) low blood calcium; convulsion caused by hands and feet, severe low will hinder the normal cardiac conduction. (3) occasional hyponatremia and hypomagnesemia situation happened. (4) bone age than actual age backward.

Due to progressive glomerular damage, while the growth of serious adverse renal glomerular filtration rate decreased about 10-year-old kidney failure that may occur.

Corneal cystine crystals (Corneal cystine crystals):
Patients often at 2-3 years of age when the symptoms of photophobia, after corneal examination, can be found in the eye corneal cystine crystals of (corneal crystals), can happen before the age of one. Untreated patients with nephropathy at 16 months after the big one can often find this characterization.

In addition, there are retinopathy (Peripheral retinopathy), repeated injury to the cornea (Recurrent corneal erosions), visual acuity and low variability characterization. Happen that some young patients with eye diseases and may even lead to blindness.

Growth retardation:
Usually found at six months

Endocrine disorders:
Low thyroid may occur, the pituitary gonadal function and insulin secretion disorders.

Others: normal intelligence, but may occur late in the disease brain atrophy and neurological lesions.

Between type / juvenile renal disease of relatively minor symptoms, the occurrence of late time, usually 6-8 at the age of onset.
Non-nephrotic variant / adult-type symptoms for this type of eye and bone marrow have on homocysteine crystals, usually occurs only photophobia symptoms.



Diagnosis:

Be able to use cysteine protein technology (cystine binding protein assay), detection of homocysteine in blood leukocytes (cystine) concentration; nephropathogenic type / child type of numerical often 50-100 times normal. This detection technology can also be used for detection of fibrous tissue, such as conjunctiva and muscle intracellular homocysteine concentration. Also available from the first three months of pregnancy from skin, amniotic fluid or chorionic cells by fibrous tissue cultured cells for prenatal diagnosis.

Treatment:

Drug therapy
Study found that cysteine (cysteamine bitartrate, drugs called Cystagon) of drug therapy for homocysteine treatment of choice for patients, this one free of the mercaptan-type material, the structure can be self-cysteine dissolved in a 90% homocysteine of more than cells, will be able to effectively control the type of patients with nephropathy disease progression.

Positive long-term treatment, can avoid or delay kidney failure and the incidence of thyroid Lower and dissolution of muscle tissue accumulation of homocysteine in order to alleviate the symptoms, to promote growth and development of the case patients.

After diagnosis, provide treatment as soon as possible; if at birth or within one month after the start, and often get the best treatment results, and contribute to the growth of the kidney to avoid the deterioration of renal function. Long-term treatment found that although there is no cure the disease, but can be avoided in patients with significant late complications.
At the side effects on nausea and vomiting may occur, but may be due to displeasure with the smell of drugs with the result of Taste; Recent studies have suggested with the use of gastrointestinal medication ─ omeprazole, to improve gastrointestinal discomfort up.

But must be noted that the cysteine of oral medication, there is no benefit from the improvement of corneal cystine crystals, it is proposed can be used in patients with CYSTEAMINE hydrogen bromide (Cysteamine hydrochloride) eye drops, in a couple of months can reduce the corneal cystine crystals, a few weeks to alleviate photophobia eyes; and wearing dark-colored or sunglasses, but also reduce sunlight circumstances brought about by photophobia.

The main goals of treatment, in order to complement because of kidney disease caused by electrolytes, amino acids, such as the loss of material, including water, sodium, potassium, phosphorus, calcium, magnesium, vitamin D ... and so on, the volume of its intake is required by patients condition and advised to regularly monitor the physical requirements to achieve.

Low happen if the thyroid, pituitary gonadal function, such as the issue of endocrine disorders may be related to endocrine accept medication.

Prognosis:

When the progressive deterioration of renal function to kidney failure, the patients are usually required to undergo blood or peritoneal dialysis and other treatment, and may need to consider the kidney transplant. After kidney transplant, even if the cystine crystals are deposited in the kidneys after transplantation on, but still will not have Fanconi's syndrome, may occur more frequently after transplantation of exclusion cases, patients need regular follow-up appointment to return to readily available treatment.