Citrullinemia
is autosomal recessive metabolic disorder urea cycle disorders (autosomal
recessive urea cycle disorder), because succinate spermine synthase gene
mutations that cause citrulline (Citrulline) can not be caused by metabolic
clinical illness.
Continuation
of ornithine cycle (ie urea cycle) a text, then we talk about the ornithine
cycle spermine synthase succinate exception arising citrullinemia
(Citrullinemia). Ornithine
cycle generally consists of four steps: ornithine and ammonia, CO2, forming
citrulline; citrulline and ammonia, forming arginine; arginine hydrolysis to
give urea and ornithine; ornithine participate in
the second round of cycle. Please go back and
review the details.
Citrullinemia (Citrullinemia)
autosomal recessive genetic disease, in the final reason is
two:
Metabolic
acid citrulline spermine synthase (argininosuccinate synthetase, ASS) gene
mutations (Mutations in the ASS gene cause type I citrullinemia), led to the
first type citrullinemia (citrullinemia type-I, CTLN-1 ), the incidence rate of 1/57, 000;SLC25A13
mutations result (Mutations in the SLC25A13 gene are responsible for type II
citrullinemia), leads to the second type citrullinemia (citrullinemia type-Ⅱ,
CTLN-Ⅱ). SLC25A13
gene may encode proteins Citrin, Citrin Aspartate can be transported from the
mitochondria to the cytoplasm, to make aspartic acid (Aspartate) and citrulline
(Citrulline) in Argininosuccinate synthetase (ASS) catalyst for
Argininosuccinate synthesis. When
the lack of Citrin, the metabolism of urea convenience blocked, causing neonatal
cholestasis (neonatal intrahepatic cholestasis caused by citrin deficiency,
NICCD) and type II citrullinemia (citrullinemia type-II, CTLN-Ⅱ), the incidence
of the latter 1/100, 000 to 1/230,
000.
CTLN-1,
CTLN-2 and NICCD clinical manifestations, diagnosis, treatment in order as
follows:
Citrullinemia
type I (citrullinemia type I) citrullinemia type II (citrullinemia type
II)ClinicalSuccinate
due spermine synthase (Argininosuccinate synthetase, ASS) exception, the body
can not metabolize citrulline, leading to accumulation of citrulline, ammonia
and toxic metabolites in the blood (ammonia and other toxic substances to
accumulate in the blood ). Hyperammonemia
manifested as poor feeding, vomiting, seizures, loss of consciousness, a lack of
energy (lethargy), ankle clonus, etc., and rapidly changing conditions,
sometimes with severe neurological abnormalities, left untreated, serious
complications deathEarly childhood onset of symptoms compared
infancy light, but obviously this period common brain lesionsCitrin protein function due to
defects caused more frequent in adults (adulthood)Neonatal
onset citrullinemia (Neonatal Hepatitis Associated with Choletasis, NICCD):
children often behave in an age before cholestasis, fatty liver, liver fibrosis,
growth retardation, hepatomegaly, abnormal liver function, blood clotting
factor
lower, hemolytic anemia, hypoproteinemia, galactosemia, multi
Hyperaminoacidemia, AFP level rise, showing a slight, so symptoms may disappear
after treatment;-year-old, the hi high protein and high fat diet, high aversion
sugar foods. Part NICCD in adult patients
with stage due to certain drugs, infections, alcohol induced heavier type II
citrullinemia appearAdult-onset
citrullinemia (adult type II citrullinemia): occurs in 20 to 50 years old.
Hyperammonemia
due to repeated easily affect the central nervous system, causing C onfusion,
abnormal behavior (including aggression, irritability, hyperactivity), memory
loss, neuropsychiatric symptoms, pumping 'A', normal or mildly abnormal liver
function, pancreatic trypsin secretion inhibin
concentrations (pancreatic secretory trypsin inhibitor, PSTI), serum [threonine]
/ [serine] ratio increased, branched-chain amino acids (Val + Leu + Ile) /
aromatic amino acids (Tyr + Phe) ratio decreasedDiagnostic
methods detect ammonia, citrulline, other amino acids, liver function, based on
but the diagnosis is dependent on examination of liver cells or skin fibroblasts
succinate spermine synthase (ASS) activity in order to detect the patient's
blood biochemistry value
equals base, including ammonia, citrulline, other amino acids concentration
detection (such as serum [threonine] / [serine], (Val + Leu + Ile) / (Tyr + Phe)
ratio), PSTI concentration, liver function, But genetic testing to find SLC25A13 mutations
basis point is confirmedTreatmentElevated
blood ammonia Acute: within 24 hours of completion of
hemodialysisPhenylacetate may
assist platoon ammoniaShould be given
high-calorie and low-protein diet (Low protein diets), to prevent brain pressure
increases, monitoring ammonia value; should avoid infectionNeonatal
onset: add fat-soluble vitamins, protein, sugar and diet containing medium-chain
fatty acids (middle-chain triglycerides, MCT); due to the high calorie diet but
increased NADH generation, affecting urea synthesis and stimulates
citrate-malate transport , resulting
in hyperammonemia, fatty liver, high triglycerides disease hyperlipidemia.
Most of the symptoms can be relieved by 1
to 2 yearsAdult-onset
type: oral arginine (arginine), sodium benzoate, sodium phenylacetate, etc. can
reduce the ammonia concentration; reduce high-calorie and high-sugar diet,
increased protein intake and other measures to improve hypertriglyceridemia.
Avoid alcohol,
because alcohol stimulate ADH activity in the liver, and promote the synthesis
of NADH harmful substances.If
the event of cerebral edema, then avoid using glycerol and fructose, to avoid
increasing the NADH generation, further causing toxic substances produced;
Mannitol is generally used to reduce brain pressure. Some patients may rely on liver
transplantation (liver transplan t) to survive
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