Acute intermittent porphyria

Introduction to acute intermittent porphyria Acute intermittent porphyria (AIP) is one of the most common porphyria diseases. The clinical features are abdominal cramps, intractable constipation, mental symptoms and excretion of large amounts of ALA and bilirubin in the urine. The disease is caused by a partial deficiency of uroporphyrinogen synthase, which is a defect of scorpion biliary deaminase. The patient's enzyme activity is approximately 50% of that of a normal person. The disease often occurs in adolescence, and it is easy to induce seizures during menstruation. Certain 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. basic knowledge The proportion of illness: the incidence rate is about 0.005%-0.006% Susceptible people: infants and young children Mode of transmission: mother-to-child transmission Complications: dehydration, epilepsy, depression

Cause of acute intermittent porphyria

(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.

Acute intermittent porphyria prevention

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.

Acute intermittent porphyria complications Complications dehydration epilepsy depression

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 hallucinations, auditory hallucinations, or arrogance, incoherent, crying Unexpected and other rickets, seizures, muscle atrophy, etc.

Symptoms of acute intermittent porphyria common symptoms abdominal pain dysphagia nausea neuralgia constipation fainting uneasiness tachycardia tension is easy to be excited

About 60% of acute attacks can find incentives, such as drinking, infection, menstrual period, hunger, etc. Some drugs can also be induced, there are sedative sleeping pills, anti-epileptic drugs, hypoglycemic agents, sulfa drugs, griseofulvin, female hormones And certain contraceptives, etc., pregnancy and childbirth can also cause seizures.

Most patients have abdominal pain as their main symptom. Paroxysmal colic can be light or heavy, but most of them are more serious and even unbearable. The pain can be localized or spread to the whole abdomen, or to the back, waist or external genitalia. Without abdominal muscle tension and peritoneal irritation, most of the abdomen did not have obvious tenderness when examined. Except for slightly flatulence, few positive findings were found, ranging from hours to days or weeks, one or more times. Irregular seizures, accompanied by nausea, vomiting, intractable constipation, bloating, duration and frequency of acute attacks are very inconsistent. Some patients still only have intermittent mild abdominal pain, but some of the first episodes are dangerous and soon die.

Symptoms of the nervous system can be varied, peripheral nerve involvement is similar to peripheral neuritis, neuropathy of the extremities, pain relief or numbness, but the disappearance of pain is less common when examined, but may be due to muscle weakness and motor symptoms. Such as muscle weakness, hanging wrist, foot or limbs loose sputum, may be accompanied by muscle pain, especially the calf, the affected muscles can shrink, tendon reflexes reduce or disappear, but can be restored when relieved, peripheral nerves Involved on both sides can be asymmetrical, abdominal, intercostal or diaphragmatic spasm causes respiratory paralysis or respiratory arrest, upper motor neurons are rare, involving the brain nerves, optic nerve palsy, optic atrophy, facial nerve spasm, hoarseness, hiccups and dysphagia, etc. Autonomic symptoms with sinus tachycardia is one of the most common symptoms, associated with vagus neuropathy, transient hypertension is also common, mental changes in personality, neurasthenia, snoring-like episodes, many patients often before acute attacks Have nervousness, irritability, excitement, and even hallucinations, arrogance, incoherence, etc. Other patients may be temporarily blind, the most serious cases may occur convulsions, and even coma, EEG may have epilepsy or electrolyte imbalance changes, neuropsychiatric and tachycardia, many patients may be misdiagnosed as neurosis or Hysteria, even considered to be intentionally exaggerated.

The patient's father or mother and brothers and sisters sometimes find that the urine contains too much bilirubin, but there may never be obvious symptoms. This condition is called recessive porphyria. The above acute symptoms include abdominal pain and peripheral neuritis. Mental disorders and purplish red urine, some people call "4P", see Table 1, 2 for details.

Examination of acute intermittent porphyria

1. When the urine is generally examined, a large amount of ALA and PBG are discharged from the urine, and the fresh urine is discharged normally. After a period of time, especially after exposure to sunlight, PBG is converted into urinary porphyrin or coproporphyrin, urine. The color gradually deepened and was brown. Under the illumination of Wood, urinary porphyrin showed red fluorescence, and the urine specific gravity increased. It 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, more meaningful for diagnosis, and can detect asymptomatic gene carriers.

Test method: Take 1ml Hoesch reagent, (phosphorus-dimethylaminobenzaldehyde 2g in 6mol/L hydrochloric acid 100ml), add 1~2 drops of fresh urine specimen, immediately present cherry red color in the reagent solution, and gently shake Cherry red spreads to the surrounding solution.

3. Quantitative examination of ALA and PBG in urine can increase the ALA and PBG by more than 100 times compared with normal people. Although it is reduced in the intermittent period, it is still higher than normal people. The normal humans discharge 0 to 2 mg per 24 hours, ALA is 0~ 7mg, PBG quantification is more meaningful for the diagnosis of gene carriers than ALA quantification, urinary porphyrinogen I synthase in patients with hepatocytes, red blood cells and fibroblasts is significantly reduced, amniotic fluid puncture cell culture for uroporphyrinogen I synthetase Quantitative, the disease can be diagnosed before delivery, and some asymptomatic children and adult gene carriers have low activity.

4. Blood biochemical examination In the acute attack, often due to vomiting and abdominal pain during the onset of eating can lead to hydropower disorders, often hyponatremia, blood calcium concentration is 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 and diagnosis of acute intermittent porphyria

The clinical manifestations of this disease are mainly abdominal cramps, peripheral neuritis, neuropsychiatric symptoms, urine reddish purple, urine sputum test, positive diagnosis, the diagnosis is not difficult, the most reliable diagnosis for intermittent and recessive cases is The content of ALA and bilirubin in urine can be determined by chromatography and established.

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 appearance of peripheral nerve symptoms, local muscle weakness, paralysis, 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.

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