acute intermittent porphyria in children
Introduction
Brief introduction of acute intermittent porphyria in children Acute intermittent porphyria (AIP), also known as hepatic porphyria, pyrrox porphyria, is more common in porphyria. In 1911, Gunther first reported that Waldenstrom comprehensively described the disease on the basis of extensive family studies in 1937. The clinical features were abdominal cramps, intractable constipation, psychiatric symptoms, and excretion of large amounts of ALA and bilirubin in the urine. basic knowledge The proportion of illness: 0.02% Susceptible people: children Mode of infection: non-infectious Complications: dehydration epilepsy
Cause
Causes of acute intermittent porphyria in children
(1) Causes of the disease
The disease is caused by partial deficiency of uroporphyrinogen synthase, which is caused by defects in scorpion sclerotium deaminase. The activity of this enzyme is about 50% of that of normal people. The technique of in situ hybridization with nucleic acid has determined the sclerotinogen deaminase. The gene is located in the 11q23-qter region and contains five exons. At least three different isozymes are known to exist in all tissues and the other in red blood cells, but Defects exist in these tissues and red blood cells, but their functional manifestations appear to be limited to the liver.
The disease is often caused by puberty, and it is easy to induce seizures during menstruation. Some drugs and hormones can induce the onset of the disease or aggravate the condition because it can promote the action of ALA synthase in the liver. The saccharide and heme ALA synthase have temporary Inhibition.
(two) pathogenesis
The disease is autosomal dominant, and the sclerotin deaminase allele is mutated on chromosome 11q24 of chromosome 11, and the activity of biliary deaminase in hepatocytes, lymph, skin, epithelium, amniotic membrane and erythrocyte is only 50% of normal people, causing obstruction of bilirubin to uroporphyrin pathway, and accumulation of bilirubin and ALA in the body due to enhanced ALA synthesis activity, it is reported that there are at least 4 types of mutations in this gene, and thus the enzyme activity In addition, some enzymes have reduced immunological activity and catalytic biological activity, some have normal immunological activities, and have reduced catalytic activity. In addition, some patients have normal erythrocyte enzyme activity, while other tissues decrease, which proves that it is possible to control more than one enzyme expression. One allele, which controls red blood cells as one gene, and controls the expression of enzymes in other tissues as another gene.
The relationship between metabolic abnormalities and neurological symptoms in patients with this disease is still not very clear. The study found that bilirubin and ALA have toxic effects on the nervous system, mainly based on ALA, including: 1 inhibiting the release of neuromuscular junction conduction media, in vitro Culture can cause neurogenesis of nerve and brain cells; 2 strong stimulant of inhibitory neurotransmitter -aminobutyric acid receptor; 3 ALA of patients with hereditary tyrosinemia and patients with severe lack of ALA dehydratase accumulate, The occurrence of neurological symptoms is similar to this disease; 4 defects in heme synthesis in the nervous system, in vitro cell culture tests show that inhibition of heme synthesis can seriously degrade cells, and the administration of heme can inhibit the nervous system symptoms of the disease, most miscellaneous Zygote gene carriers lack symptoms, but certain factors can promote their onset.
Prevention
Acute intermittent porphyria prevention in children
The disease is an autosomal dominant hereditary disease. The prevention method refers to the prevention method of hereditary diseases. Those suspected of this disease should pay attention to avoid the application of certain drugs, such as barbiturates, sulfonamides, aminopyrines and steroids. Progesterone can prevent the onset of this disease.
Complication
Acute intermittent porphyria complications in children Complications dehydration epilepsy
Dehydration and oliguria due to vomiting, seizures, limb paralysis and respiratory muscle paralysis, may have personality changes, such as depression, nervousness, crying, and there are illusions, auditory hallucinations, or arrogance, incoherent, crying Unexpected and other rickets, seizures, muscle atrophy, etc.
Symptom
Symptoms of acute intermittent porphyria in children Common symptoms Nausea, restlessness, abdominal pain, oliguria, constipation, dehydration, depression, sensory disturbance
There are few episodes before puberty, and the episodes are intermittent. The main manifestations are seizures, abdominal cramps of different degrees, painful parts, and can be radiated to the back, bladder or external genitalia. Patients often sit fiercely and even cry out loud because of severe abdominal pain. The duration of seizures varies from hours to days or even weeks, often accompanied by nausea, vomiting and constipation. Dehydration and oliguria can occur due to vomiting. Severe abdominal pain is often misdiagnosed as acute abdomen and surgery, abdominal distension, bowel The sound is weakened or disappeared. Although there is extensive tenderness, it is not proportional to the degree of pain. There is no abdominal muscle tension, white blood cells are not increased, and it is easy to be misdiagnosed as abdominal epilepsy or rickets. X-ray examination shows small intestine inflation or liquid level, about 20 The incidence of patients with neurological symptoms is mainly caused by autonomic dysfunction. In addition to intestinal fistula, heart rate is fast, blood pressure is increased, and urinary retention can occur. A small number of patients have seizures as the main complaint, and EEG at the time of onset. There may be changes, the symptoms will return to normal after remission, the peripheral nerves may be affected by limb pain, facial nerve paralysis, and one or more limbs flaccid paralysis. There are also paralysis of the limbs and paralysis of the respiratory muscles. The tendon reflexes are weakened or unable to be elicited. The affected muscles quickly shrink, but they recover quickly after remission. The upper motor unit is extremely rare, and about 50% of patients have sensory disturbances. More limited to limbs.
Psychiatric symptoms are more common in patients with intestinal fistula, and may have personality changes, such as depression, nervousness, crying, and there are hallucinations, auditory hallucinations, or arrogance, incoherent, cries and laughter, etc. If the diagnosis is not timely, Taking phenobarbital, phenytoin or chlordiazepoxide for the above symptoms, the symptoms will be aggravated, and mental disorders may occur, and even life-threatening nervous system symptoms such as respiratory muscle paralysis and cranial nerve palsy may occur. The symptoms are quickly relieved.
Examine
Examination of acute intermittent porphyria in children
1. General urine check
At the time of onset, a large amount of ALA and PBG were excreted in the urine, and fresh urine was discharged normally. After a period of time, especially after exposure to sunlight, PBG was converted into urinary porphyrin or coproporphyrin, and the urine color gradually became dark. Under the illumination of Wood, urinary porphyrin showed red fluorescence, and the urine specific gravity increased, which may be caused by excessive secretion of vasopressin, but the pituitary lesions could not be confirmed.
2. PBG qualitative test (Watson-Schwartz test)
This test is specific, meaningful for diagnosis, and can detect asymptomatic carriers of the gene.
Test method: Take 1ml Hoesch reagent (phosphorus-dimethylaminobenzaldehyde 2g in 6mol/L hydrochloric acid 100ml) and add 1~2 drops of fresh urine specimen. Immediately present the cherry red color in the reagent solution, and gently shake it. Cherry red expands to the surrounding solution.
3. Quantitative examination of ALA and PBG in urine
ALA and PBG can be increased by more than 100 times compared with normal people. Although it is decreased in the intermittent period, it is still higher than normal. Normal people have 0 to 2 mg of PBG per 24 hours, ALA is 0 to 7 mg, and PBG is quantified for gene carriers. Diagnosis is more meaningful than ALA quantification. The urinary porphyrinogen I synthetase in patients' liver cells, red blood cells and fibroblasts is significantly reduced. The amniotic fluid puncture cell culture is quantified by uroporphyrinogen I synthetase, which can be diagnosed prenatally. Some asymptomatic children and adult gene carriers have low activity.
4. Blood biochemical examination
In acute attacks, often due to vomiting and abdominal pain during the onset of eating can lead to hydropower disorders, often hyponatremia, blood calcium levels are also reduced, and even some patients may have oliguria and azotemia.
According to the clinical manifestations of symptoms and signs, you can choose to do B-ultrasound, X-ray, electrocardiogram, EEG, CT and other tests.
Diagnosis
Diagnosis and diagnosis of acute intermittent porphyria in children
diagnosis
For patients with abdominal cramps who can't find the cause of recurrent episodes, with neuropsychiatric symptoms, those who have brown urine after placement should consider the disease. Take the fresh urine and make a Watson-Schwartz test to confirm the diagnosis. If you take a barbiturate, Aminopyrine or sulfa drugs, a history of increased disease, is more helpful for diagnosis.
Differential diagnosis
1. In case of abdominal pain, pay attention to the identification of various acute abdomen: such as kidney stones, gallbladder common bile duct stones, acute pancreatitis, stomach or duodenal ulcer, acute appendicitis, intestinal obstruction, etc., and even misoperation .
2 Unexplained dysfunction of the nervous system: especially the symptoms of peripheral nerves, muscle weakness in the body, sputum, etc., should pay special attention to the possibility of porphyria.
3. Poisoning patients also have abdominal pain, constipation and neurological symptoms, and the excretion of ALA in the urine is also increased, but the results of the dimethylaminobenzaldehyde test are usually negative, and attention should be paid to the identification.
