Tsitrullinemiya

Description:

Tsitrullinemiya — a rare autosomal and recessive disease with deficit of an argininsuktsinatsintetaza. Utilization of citrulline is blocked. Mental retardation is characteristic of a disease. Genetically the zayobolevaniye is various (practically in any link of exchange of urea); the clinical picture of a tsitrullinemiya also differs in a big variety during the different periods of life.

Tsitrullinemiya reasons:

The reason of development of a tsitrullinemiya — multiple mutations in a chromosome of 9 q34.

Insufficiency of an argininsuktsinatsintetaza therefore there is a sharp increase in citrulline in plasma and the strengthened removal of this amino acid to urine is the cornerstone of a disease.

Tsitrullinemiya symptoms:

Exist considerable clinical and genetic polymorphism from asymptomatic forms to tsitrullinemiya forms, heavy with a lethal outcome.

The severe form of a disease of a tsitrullinemiya (type I), demonstrates since the birth and proceeds with the expressed clinical symptomatology from the death in the neonatality period.

Tsitrullinemiya II of type meets in later terms and is caused by decrease of the activity of an argininsuktsinatsintetaza only in a liver. Mental retardation and neurologic symptomatology is characteristic of all forms. At the full block of enzyme in the first day of life against the background of feeding by breast milk there comes block, hypotonia, spasms, a coma. Death can come in the first days of life. At a morphological research of a brain of the died children the neural degeneration and disturbances in myelination comes to light.

Diagnosis:

The high giperammoniyemiya (more than 1000 mg/dl) is characteristic of a neonatal form.
At an acute neonatal form in blood, urine, liquor citrulline level is increased.
The moderate argininsuktsinaturiya comes to light.
In blood argininesuccinic acid is absent.
Levels of a glutamine and alanine in serum are higher than norm.
Content of orotovy acid in urine is increased.
Laboratory tests at a tsitrullinemiya correspond to a liver disease.
Decrease of the activity of enzyme is observed at a biopsy of a liver and in culture of fibroblasts of skin.

Prenatal diagnosis of a tsitrullinemiya is carried out by a citrulline research in an amniotic zhidyokost or culture of amniotsit. Identification of a carriage of defective genes is reasonable.

On EEG, as a rule, reveal diffusion epileptic changes. At a magnetic and resonant research of a brain on the T2-weighed images find sites of a symmetric hyper intensive signal in a thalamus in patients, basal ганглиев, bark and subcrustal white matter, subcortical cysts. Changes are more expressed in occipital shares.

The diagnosis establish on the basis of set clinical and datas of laboratory, in particular giperammoniyemiya combinations to a gipertsitrullinemiya. For confirmation of the diagnosis it is possible to use definition of activity of an argininosuktsinatsintetaza in culture of fibroblasts, and also identification of mutations of a gene of ASS by molecular and genetic methods.

Treatment of a tsitrullinemiya:

Non-drug treatment.

The patient appoint low-proteinaceous clinical nutrition. Products of preferential plant origin enter their diet. Protein content as a part of natural products makes about 1 g/kg a day depending on individual tolerance. Proteinaceous insufficiency is liquidated use of a special semi-synthetic product (Dialamine, Essential Amino Acid Mix) which part irreplaceable amino acids are. Total quantity of protein in a daily diet of the child bring to 2,5–3 g on 1 kg of body weight on the 1st year of life and to 2 g/kg at more advanced age (protein of natural products + a hydrolyzate protein equivalent).

Drug treatment.

Patients have to receive the HP stimulating urea synthesis (arginine in a dose of 250-300 mg/kg a day), the activating binding of ammonia and removal from an organism of nitrogenous compounds in the form of non-toxic metabolites (sodium benzoate, фенилацетат sodium ℘ or фенилбутират sodium ℘ in a dose of 200-250 mg/kg a day, a left carnitine in a dose of 20-30 mg/kg a day), and also the stimulating biosynthesis of aspartic acid and utilization of citrulline (sodium citrate ℘ in a dose of 2 mmol/kg a day). Purpose of citrulline and a haloperidol is contraindicated to patients.

In an acute state patients need the intensive care including procedures of a hemodialysis or peritoneal dialysis for decrease in level of ammonia in blood. Inefficiency of dietary and medicamentous therapy is the basis for transplantation of a liver.