Citrullinemia

Citrullinemia urea cycle metabolism is one of these diseases is due to enzyme deficiency
Cause . Urea cycle, citrulline (citrulline) is Carbamoyl phosphate and
Ornithine ( ornithine ) after effects of the product. Under normal circumstances, citrulline further by spermine
Succinic acid synthase (argininosuccinate synthetase) and aspartic acid (asparate)
Combine to produce succinic acid spermine (argininosucinate, AS). Urea per molecule , including the
Two atoms of nitrogen (N), one from ammonia (NH3), one comes from aspartate
(asparate). argininosuccinate synthetase deficiency leads to the accumulation of citrulline , called
Citrullinemia first type .
        Most nitrogen from protein and amino acid metabolism, and the body to remove nitrogen urea cycle is the main road
Trail. Urea cycle in the liver in the performance , some of the reaction in the mitochondria , has a portion that is the fine
Cytoplasm inside, able to toxic substances ( ammonia ) , converted into a more toxic substances ( urea ) , followed by small
Then discharged . Mitochondrial metabolic disorder that may affect the urea generation , resulting in hyperammonemia . Overall speaking,
Urea cycle is subject to N- acetyl glutamate (N-acetylglutamate, NAG) synthesis rate adjustment
Control , this enzyme catalyst (NAG) turn ammonia into urea cycle .
         Argininosuccinate synthetase generally will be transported to the brain , kidney , skin and fibrous tissue
Mother cell effect, so citrulline outside can be metabolized in the liver . Citrullinemia patients with genetic defects
Among these organizations are manifested in . Urea cycle, citrulline and aspartate binding, the second
Waste nitrogen molecules into circulation ; damaged when the urea cycle , resulting in a reduced ability to excrete ammonia, 50% of patients
There hyperammonemia situation.

Genetic model
        Japan had cases in adults found a specific , previously undetected and treatment citrulline blood
Disease , there are patients in the 48 years after the discovery . Some patients have developmental delays during childhood years in question, but
Is that most of the patients before the onset of symptoms to the disease . So citrullinemia age of onset and birds
Formyl amino acid transfer enzyme deficiency (Orinithine transcarbamylase deficiency) a
Sample is unpredictable . Mortality and morbidity ratios are high .
        Citrullinemia is an autosomal recessive genetic disease , both parents are carriers of the recessive
(Carrier: parents, each with a defective gene , but no clinical symptoms ) , the patient must be
With two defective genes ( each get one by the parents ) until disease. As long as both parents are carriers, there is
25% chance of giving birth to sick children , there is a 50% chance for the child carriers . No gender diseased probability
Points.
        Citrullinemia causative gene is located in the ninth chromosome (9q34). At least 20 sudden
Point was found. Age of onset urea cycle with other metabolic disorders same variable age of onset ,
The most common age of onset neonatal period . Neonatal period and grew up in Children with no treatment , there may be wisdom
Force barrier consequences.
Symptom
       
        Symptoms of high blood ammonia , along with lack of appetite , vomiting , fatigue, irritability , cramps ; cerebral edema and faint
Fans , if untreated may lead to death. Typically onset neonatal period , but symptoms may be a few days
After a few weeks before or after being noticed . Clinical symptoms and severity vary depending on individual circumstances . Generally
May appear hyperammonemia status, growth is poor. If the brain edema may cause papilledema
(Papilledema), intracranial pressure will increase. Lungs , it may have shortness of breath or too strong
Circumstances may apnea or late failure. Moderate hepatomegaly may also occur a phenomenon . Neurological side
Surface , there may be poor coordination , rotation movement disorder (dysdiadochokinesia), the tension is too low or
Too strong , ataxia , tremors , convulsions , drowsiness . The main complications of neuropathy, including intellectual impairment
Obstruction , acute hyperammonemia coma , or even death.
Diagnosis
         For symptomatic patients , the primary measurement of the blood that is ammonia (NH3) concentration was useful for diagnosis
Biochemical values. Again is a measure of the concentration of amino acids in the blood , the incidence of patients whose serum citrulline significantly
Rise to 1000-5000  M ( normal 10-20  M). Amino acid concentration in the urine of patients ,
Concentrations of organic acids and urine orotic acid (orotic acid) can also be used as reference values. Orotic acid in the urine of patients
Concentration will rise.
        Measurement of skin fibroblasts of Argininosuccinate synthetase, can provide clear
Biochemical diagnosis.
Prenatal diagnosis
May have an amniocentesis (amniocytes) or chorionic villus do molecular diagnostics .
Treatment
        The goal of treatment is to fix biochemical imbalance and to ensure nutritional needs. Situation in hyperammonemia
Under the immediate restricted diet of protein, non-protein source of heat strengthened to avoid decompensation . Serious
It may quickly remove ammonia in hemodialysis .

Low-protein diet
        According to the patient 's age and the severity of the disease protein intake determine each patient 's needs
Requirements are quite different . Six months ago, because it is a period of rapid growth , the patient may need
1.5g/kg/day or more protein ; preschool period , protein intake is usually reduced to
1.2 ~ 1.5g / kg / day; school-age children , you can be reduced to 1 g / kg / day. After puberty , the protein
Amount can be less than 0.5g/kg/day.
Drug
Drugs provide an alternative way to eliminate waste nitrogen .
1.Sodium benzoate (Ucephan): with glycine (glycine) combine to form hippuric acid
(Hippurate), and then by the urine. Every 1 mole of benzoate remove one mole of nitrogen. Generally
The IV dose to 250 mg / kg / day; oral doses of 375mg/kg/day, taking 3-4 minutes ,
And with a low-protein diet. Side effects are nausea , vomiting, tinnitus , visual disturbances .
2.Sodium phenylbutyrate (Buphenyl): in the liver may be oxidized to
phenylacetate, then combine and glutamine , the final product phenylacetylglutamine
Excreted in the urine . Every 1 mole of phenylbutyrate remove two moles of nitrogen. Given dose is 0.5
mg / kg / day.
3 Arginine (Arginine): via arginase enzyme (arginase) role after finishing each 1mole
Acid into 1mole of urea and ornithine 1mole (ornithine). Hyperammonemia circumstances,
Given dose of 600 mg / kg / day. Children with stable given oral doses of 400-700
m g / kg / day.
        Prognosis and age of diagnosis of illness related . In the neonatal period had symptoms of patients
, Its prognosis is poor , the majority of patients will have some significant complications . Require long-term with physicians
And nutritionists with continued outpatient follow , regular biochemical tests, recording height and weight development,
Grasp the patient's condition .