Etiology

For congenital metabolic disorders of genetic disease, patients melon acid metabolism (citrulline) of the gene mutation, resulting in de acid concentrations continued to rise, resulting in high blood ammonia and other clinical abnormalities. Melon acid metabolism-related diseases, including abnormal; melon acid type hyperlipidemia (citrullinemia type I), melon acid type II hyperlipidemia (citrullinemia type II), and spermine succinate enzyme deficiency (Argininosuccinic aciduria ) and so on.


Incidence:

At present, melon acid Hyperlipemia notice has been included as a rare disease in our country, Taiwan, the incidence is about 1 / 14000.

By neonatal screening center at National Taiwan University Hospital experience, we at 5 years, screening of 330,000 newborns, identified as melon acid hyperlipidemia in children with a total of 6 people (incidence rate of 1 / 54852), belong to one of the second type melon acid attack type neonatal hyperbilirubinemia in children with a total of 3 people.

Genetic model:

Melon Hyperlipemia acid type and the second type, are autosomal recessive genetic diseases, said that parents with a mutation for the gene, no clinical symptoms due to the band, but each of its next-generation fetal regardless of gender will have 1 / 4 chance of suffering from this disease.


Characterization of clinical on:

Melon acid type hyperlipidemia (Citrullinemia Type I):
Obstacles for the urea cycle (Urea Cycle disorder) diseases due to spermine synthase succinate (Argininosuccinate synthetase; ASS) function caused by abnormal; patients can not be transformed into melon acid succinate spermine, resulting in de acid accumulation and high blood ammonia disease.

Temporal variation in patients with significant morbidity, and some will be 24 hours of birth at the onset of symptoms, but also to early childhood or late onset case in point. If the incidence during the neonatal period, early symptoms are generally poor feeding, vomiting, drowsiness, restlessness, shortness of breath and so on, their condition would normally be quickly changed, and show more serious neurological problem with the autonomic nervous system , if there is no proper treatment, most patients will have complications or death.

Early childhood onset patients, the symptoms in general and infant during the comparison, the comparison is not so serious. Patient diagnosis is usually already have obvious brain lesion. Up to now, and can not predict when will the incidence of patients.

Melon acid type II hyperlipidemia (Citrullinemia Type II):
Since the body of this type are Citrin caused by lack of protein function. Neonatal period can be broken down into type attack (Neonatal Hepatitis Associated with Choletasis; NICCD), and adult onset type (Adult-onset Type II Citrullinemia).

Neonatal seizures in patients with type 1 at birth to five months will happen between cholestasis jaundice, abnormal liver function, the problem of high amino acid levels, galactosemia and symptoms such as fatty liver. In severe cases, lead to growth retardation, abnormal bleeding or more than anemia, hypoglycemia, hepatomegaly, and even liver failure. Treatment, including supplementary fat-soluble vitamins, as far as possible to maintain high protein high fat diet. Most patients with symptoms can be at 1 ~ 2 years old and will be eased.

At present, for these patients whether or not to develop into adult-type attack is still unclear, long-term follow-up required in order to understand the evolution of disease and early treatment.

Adult onset type of patients because of repeated episodes of high blood ammonia, caused by a sudden sense of anxiety, behavior abnormalities, memory loss or other neuropsychiatric symptoms, and may even lead to pumping sustain or death. Generally speaking, the adult onset type occurs in 20 ~ 50 years old, and may be accompanied by other liver problem.

Diagnosis:

Melon acid hyperlipidemia type:
Diagnostic methods, including testing blood ammonia values, melon acid value, and other related amino acids and liver function tests. Way to confirm the diagnosis need to liver cells or skin fibroblasts to spermidine synthase activity of succinate inspection.
Melon acid type II hyperlipidemia:
Diagnostic methods, including testing blood ammonia values, melon acid value, and other related amino acids and liver function tests. At present, genetic tests done to confirm the diagnosis, about 80% of the cases, point mutations can be found.



Treatment:

Melon acid hyperlipidemia type:
When the acute increase in blood ammonia when necessary to hemodialysis to remove ammonia. High blood ammonia of time if more than 24 hours will result in neonatal brain injury, peritoneal dialysis can not be effective to remove ammonia. Newborn hemodialysis are highly professional medical acts, have required special equipment, and has experience in cardiac surgery, pediatric nephrology and pediatric genetic general practitioners in order to achieve the mission of the co-operation.

Patient situation more stable, may be the use of special drugs (phenylacetate) assist the body from ammonia. To be particularly noted that the supply of heat and moisture sufficient to reduce protein catabolism and to avoid increased intracranial pressure.

At long-term treatment, the patients need to limit protein intake, the use of special formula to add the necessary growth and development and use of special drugs to help the ammonia emission, and regular monitoring of ammonia, such as numerical. Peacetime should also avoid infection, to prevent the problem of high blood ammonia happen.

Melon acid type II hyperlipidemia:
The majority of patients with neonatal seizures, through the fat-soluble vitamin supplement, and the use of lactose-free and contains medium-chain fat (middle-chain triglycerides; MCT) the special milk powder, the average in the 12 months of age will be able to achieve a good outcome of the treatment ; a small number of cases even without specific treatment, symptoms can be gradually improved.

Adult onset type in patients with liver transplant if the treatment will be effective in preventing the occurrence of high ammonia problem and the problem corrected metabolic abnormalities. Study found that oral arginine will help reduce the accumulation of ammonia, and reduce heat and increase protein intake, you can improve hypertriglyceridemia (Hypertriglyceridemia).

In general, the urea cycle in patients with metabolic disorders (including melon Hyperlipemia acid type) to avoid the occurrence of high blood ammonia, preferably a low protein / high calorie diet, but this one diet but the lack of citrin protein function melon acid type II hyperlipidemia harmful; high-calorie diet, will increase the melon acid in patients with hyperlipidemia type II NADH generation, interference with normal urea synthesis, and stimulate the transport of citrate-malate, which lead to high blood ammonia, and fatty liver, high triglyceride disorder happened.

When the melon acid in patients with hyperlipidemia type II acute symptoms and cerebral edema (brain edema) of the problem, we should avoid the injection of glycerol and sugars (glycerol and fructose), so as not to increase the generation of NADH, which led to abnormal liver function and toxic substances; general recommendations are relatively safe Mannitol reduced selection pressure in the brain.

Prognosis:

Melon acid in patients with hyperlipidemia type usually should avoid excessive intake of protein, and the occurrence of infection and should be back to regular attendance tracking, to monitor the growth and development, ammonia and related amino acids necessary for the value, in order to maintain normal physiological requirements, in peacetime should be aware of high blood ammonia imminent Characterization; include: awareness of changes, headache, bad spirit (lethargy), drowsiness (nausea), vomiting, poor appetite, poor feeding (refusal to feed) and ankle cramps (ankle clonus) and so on. When the more serious diseases, the liver transplant of disease will be of great help.

Melon acid in patients with hyperlipidemia type II usually recoverable high-fat, high protein and low carbohydrate diet, fasting, or fasting in order to reduce the situation to avoid the occurrence of high ammonia problem. In addition should avoid alcoholic drinks or food, to avoid alcohol because alcohol stimulate dehydrogenation (alcohol dehydrogenase; ADH) activity in the liver and increased synthesis of NADH to produce harmful substances.