Disease etiology principle
Tingting
told parents this is a flowchart of urea metabolism and circulation, this figure
is to tell us when the body is then broken down into amino acids intake of
protein for human use, and then metabolized through the liver will convert toxic
ammonia that is urea into non-toxic
substances, and by urine. In
the urea cycle, must by many enzymes to help break down the body's functioning,
such as: NAGS (N-acetylglutamate synthetase; N-acetyl glutamate synthesis
transaminase), CPS (Carbamoyl phosphate synthetase; A unitary unitary first
phosphate synthetase each),
AS (Argininosuccinate synthetase; spermine acid synthase), AL (Argininosuccinate
lyase; spermine amber hydrolysis transaminase), Arginase (Arg), OTC (Ornithine
transcarbamylase; ornithine amino acyl transfer A transaminase deficiency) of several enzyme transaminase.
Occurs when each
part of the enzyme deficiency, can not successfully make the ammonia metabolism
disease, and will reflect the upstream detection index is high, the low value of
the downstream testing situations. By
Tingting speaking on our blood amino acids from her LC MS / MS inspection
reports that Glutamine (glutamine) 2460umol / L (normal is less than one year
old 31-560umol / L) and Citrulline (citrulline) 1430umol /
L (normal is less than one year old 11-27umol / L) and many other indicators are
high in Arginine (Arg) 1.16umol / L (normal is less than one year old 5-73umol /
L) index is low. Therefore,
we will be highly suspected Tingting argininosuccinate synthase (succinate
spermine synthase) exception occurs citrulline concentrations continue to rise,
leading to high blood ammonia and other abnormal clinical signs, these are
likely to belong to gene mutation. Citrulline-related
diseases, including metabolic disorders; citrullinemia type I (citrullinemia
type I), citrullinemia type II (citrullinemia type II), and spermine enzyme
deficiency succinate (Argininosuccinic aciduria ),
etc.
The incidence of
disease and genetic patterns
Citrullinemia
(Citrullinemia) in Taiwan occur in approximately 1/14, 000, are of rare diseases
subsequently. Citrullinemia
(Citrullinemia) mode of inheritance is autosomal recessive disease, which means
that parents will each with a mutated gene, and the clinical symptoms will not
have symptoms, it is called with the result of those. The human
body has 22 pairs of autosomes and one pair of sex chromosomes, after mitosis
embryonic development process, chromosomes from the father and the mother would
choose each half to form 22 pairs of chromosomes of the fetus. If the father and mother
happened with the mutated gene is passed to the next generation, the formation
of autosomal recessive mode, you will be sick. In other words,
regardless of gender, Tingting's parents at each tire will be 1/4 chance of
suffering from birth citrullinemia (Citrullinemia) this
disease.
Characterization of clinical
disease
Citrullinemia
type I (Citrullinemia Type I) citrullinemia type II (Citrullinemia Type
II)Main
reasons: succinate spermine synthase (Argininosuccinate synthetase; ASS)
dysfunction caused. Citrin vivo
protein (lemon prime carrier protein) functional deficiency
caused.Time of
onset of the great difference in time of onset patients, after 24 hours from
birth to early childhood before onset. Can
be divided into early onset: neonatal onset (Neonatal Hepatitis Associated with
Choletasis; NICCD), and late onset: adult onset (Adult-onset Type II
Citrullinemia).If
the clinical characterization of onset in the neonatal period, the early
symptoms are generally poor feeding, vomiting, drowsiness, restlessness,
shortness of breath, rapid changes in conditions or serious neurological
problems with the autonomic nervous system. Without proper treatment, most will die or produce
complications.If the
childhood disease, the symptoms will be relatively not so serious, but it may
have been obvious brain lesions.If you were born in the neonatal onset
of about one to five-month period, appears cholestatic jaundice, liver
functionDiagnostic methods in
common: blood test for ammonia values citrulline values, and other related
amino acids and liver function testsGene seat: 9q34 7q21.3 of SLC25A13
gene mutationsOther liver cells or skin
fibroblasts for spermine acid synthase activity checks.Treatment: 1. Acute increases when
ammonia is necessary to remove the ammonia hemodialysis. Hyperammonemia time if more than 24 hours,
will be on neonatal brain damage.(2) the use of special drugs
(phenylacetate) help the body discharge of ammonia.1
neonatal onset patients, fat-soluble vitamin supplementation, and the use of
lactose-free and contains medium-chain fatty (middle-chaintriglycerides; MCT)
special milk powder, an average of 12 months old when good treatment can
attainable effectiveness; few cases
even without specific treatment, the symptoms can be gradually
improved.2 adult onset patients,
if after liver transplantation therapy can be effective in preventing high blood
ammonia problems, and correct metabolic abnormalities issue.3
Oral arginine will reduce the accumulation of ammonia, and reduce heat and
increase protein intake, you can improve high blood triglycerides
(Hypertriglyceridemia).Diet
therapy should adopt high-calorie, low-protein diet. Should adopt high-fat, high-protein and low-carbohydrate
diet.Precautions
to track return visits regularly, monitor growth and development, ammonia and
related values essential amino acids to maintain normal physiological needs,
usually should pay attention to the impending hyperammonemia characterization;
include: altered consciousness, headache, bad (lethargy),
drowsiness (nausea), vomiting, poor appetite, poor feeding (refusal to feed) and
ankle cramps (ankle clonus) and so on.1 to avoid excessive intake of protein, and
infection problems.(2) when
the disease is more severe, a liver transplant will be of great help for the
disease.1.
Adopt low protein / high calorie diet, protein function citrin deficiency type
II citrullinemia harmful.(2)
high-calorie diet, will increase citrullinemia patients with type II NADH
generation, interfere with normal urea synthesis and stimulate citrate-malate
delivery, and lead to high blood ammonia, and fatty liver, high triglycerides
the occurrence of disease.3
When citrullinemia type II patients with acute symptoms and cerebral edema
(brain edema) problems should avoid injection of glycerol and sugars (glycerol
and fructose), so as to avoid increasing the generation of NADH, resulting in
abnormal liver function and produce toxic
substances.4 reduces fasting
or fasting, avoid high blood ammonia problems.5
Avoid alcohol or alcoholic foods, because alcohol dehydrogenase alcohol can
irritate (alcohol dehydrogenase; ADH) activity in the liver and promote
increased synthesis of NADH to produce harmful
substances.
Outpatient cases
basic information
Basic
information:Name: Tingting Gender: Female
Age: 3 days
Tingting was born on the third day
of female infants, due to a sudden emergency pumping spasm and then was
transferred to a coma NICU. In
the neonatal intensive care unit for treatment and medical treatment process,
Tingting body found in ammonia (ammonia) index is high is cause sudden coma
reasons, but Tingting why hyperammonemia symptoms of it? Went against metabolic
diseases Looking in the urine
organic acid detection and tandem mass spectrometry newborn screening are
confirmed citrullinemia (Citrullinemia). Tingting
Why get this disease through genetic testing that each parent with a gene
mutation point C.380G> A, p.R127Q, Heterozygous Tingting who presented with
mutations point C.380G> A ,
p.R127Q, Homozygous is the same. Thus, for the first type
Tingting confirmed citrullinemia (Citrullinemia) and belong to one of the rare
disease hereditary disease. Currently
Tingting home successfully and no recurrence of hyperammonemia condition, weight
5.2kg, eating some food orally for every three hours 120CC, occasionally
overflows, no spitting, no oliguria, slightly loose stools, etc. . Tingting's parents want to
know more about "citrullinemia (Citrullinemia)" relevant information and
follow-up care of the problem.
Family
Trees
(To
respect the privacy of cases, case names begin with a pseudonym processing,
spectrum and content of the story of his family has been
changed)
Genetic outpatient
consultation process
A nutritional care
sections:Tingting has been
identified as citrullinemia type I patients, is now one month old. Fortunately Tingting after the
first attack, there is no significant complications occurred, and no recurrence
of hyperammonemia phenomenon. Tingting Tingting's
parents already know is necessary to use special nutritional formula, milk
Tingting staple part from the high-calorie, low-protein diet adjustments.
In
nutrition, you must calculate and discuss in detail through nutritionist, so
Tingting growth process in a lifetime, to be able to have enough calories and
protein metabolism process does not cause a burden. Future
growth process, parents must learn how to record and diet, how to cook food, how
to teach Xiao Ru food choices, how to observe and avoid intake of other foods
Tingting privately, and how schools (kindergarten or elementary school) in the
nutrition section do adjustments, and even some
parents to prepare their own. We all know these processes Tingting
parents is hard, but it is also one of the best ways for
Tingting.
Two. Disease drug therapy
sections:Another object is to
provide drugs eliminate waste nitrogen way. Common
drugs (1) Sodium benzoate (Ucephan): mainly associated with glycine (glycine) to
form hippuric acid (hippurate), through the urine. This type of drug has
intravenous and oral dosage forms taken 3-4 times a day, while the side effects
are nausea, vomiting, tinnitus, visual disturbances. (2)
Sodium phenylbutyrate (Buphenyl): mainly in the liver may be oxidized to
phenylacetate, and then combined with glutamine to form phenylacetylglutamine
final product by the urine. (3)
Arginine (Arginine): arginine by the enzyme (arginase) the role of the arginine
into urea and ornithine (ornithine). These drugs must be
long-term outpatient follow with doctors and nutritionists with through regular
biochemical tests, recording height and weight development, adjusted to fit
Tingting situation.
Three. Liver
transplant:The purpose is
to help liver transplant originally Tingting protein metabolism in the liver,
the situation has improved and is therefore indeed can change Tingting
lifestyle, do not need to rely on diet control. But
there are certain things that must be thinking, such as: (a) who fits the liver
transplant Tingting, mostly pro-lineal five other blood diseases within and
without (B type hepatitis disease or carriers, AIDS etc.), blood and other parts are in compliance with those.
(2) How much needed liver
transplants, most have adopted adults and only 1/3 of the can. (3) what is to
be done prior to transplantation should be assessed with the experts appropriate
time, and Tingting recommended that at least 10 kg body weight or more, between
the donor and recipient is low compared to exclusion. (4)
the time of transplantation, donor and recipient by key required
hospitalization, blood drive with the computer off when physical conditions such
as evaluation, recipients must first chemotherapy will minimize its own white
blood cells of the state has been favorable transplant success rate . (5)
after transplantation, the donor must trace back to the clinic for some time,
recipients must be hospitalized longer period of observation and must start
taking anti-rejection drugs for life, to avoid being infected with the situation
with regular visits tracked. (6)
When will I know there is rejection reactions occur, such as: fever, infection,
complications such as biliary obstruction, physical condition because each
different severity of sequelae, some even death. Therefore,
Tingting Tingting's parents to look at the situation now is very stable and not
more than 10 kg body weight, do not need to rush to some liver transplant, when
Tingting encounter recurrent episodes of hyperammonemia or no longer
such as by the oral intake
deteriorated conditions, it is the time when you need to perform a liver
transplant. So, Tingting's
parents, you can consider this treatment and can do this partly for the previous
preparation, looking for a suitable donor, do preventive
preparations.
Four. Development and
tracking components:Tingting
diseases due to the relationship, let her grow by some obstacles, but compared
with the same age children seem smaller, shorter, but if the parents are in
accordance with the instructions given nutritionist care is basically Xiao Ru
will not did not grow. Therefore, they are better than expected with Tingting
is growing can be.Tingting intelligence in part is
less affected, unless the emergence of long-term hyperammonemia caused severe
brain injury sequelae. Therefore,
parents in infancy or Tingting, you must learn how to observe the symptoms of
high blood ammonia and know how to deal with an emergency to a medical
institution, and remind Tingting diseases and medical staff to be temporarily
fasting glucose given intravenously given
Sodium benzoate, Sodium phenylbutyrate, L-arginine and other drugs, and even
reducing intracranial pressure dialysis and drug use and so on.Tingting patient
examination takes about a month back and observe the control situation, to see
if you need help train other relevant departments, such as early intervention
for developmental assessment.
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