Hepatic porphyria

Introduction to hepatic porphyria Porphyria is a disorder of porphyrin metabolism disorder characterized by increased excretion of porphyrin and porphyrin precursors in urine and feces. Porphyria is a congenital disease that is mainly caused by a lack of various enzymes involved in heme synthesis and has a family history. The disease can be divided into 4 types: 1. Acute intermittent type. 2. Delayed skin type. 3. Mixed variants. 4. Hereditary fecal porphyrin type. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: non-infectious Complications: constipation, bloating

Causes of hepatic porphyria

(1) Causes of the disease

1. Acute intermittent type: Acute intermittent blood porphyria is more common, which is an autosomal dominant genetic disease caused by a deficiency of PBG deaminase (urinary porphyrinogen synthase). This defect causes a decrease in intrahepatic PBG to uroporphyrinogen III, and the resulting heme synthesis disorder causes an increase in the action of ALA synthase, resulting in an increase in the synthesis of ALA and PBG and an increase in excretion from the urine.

2. Delayed skin type: Delayed skin type blood porphyria is the most common hematoporphyrin disease caused by a deficiency of intrahepatic uroporphyrinogen decarboxylase. Is autosomal dominant inheritance. The cases were sporadic, with more males than females, and most patients had no family history. Although some people have biochemical defects in which the enzymatic activity of uroporphyrinogen decarboxylase is reduced, the excretion of urinary porphyrin does not necessarily increase, and clinical symptoms are not necessarily obvious. Synergistic effects of genetic defects and alcoholism, excessive intrahepatic iron overload, liver damage, and female hormones further reduce the activity of urinary porphyrin decarboxylase or stimulate the formation of ALA, resulting in a significant increase in the formation of urinary porphyrin. , which leads to the onset of delayed cutaneous porphyria.

3. Mixed or variant: Mixed porphyria is a disease caused by a decrease in protoporphyrinogen oxidase and heme synthase, which is inherited by autosomal dominant and can be diseased by both sexes.

4. Hereditary fecal porphyrin type: Hereditary fecal porphyria is a rare porphyria disease. An autosomal dominant genetic disease caused by a deficiency of coproporphyrinogen oxidase. Some patients have photoreceptive skin lesions, and their clinical manifestations are similar to those of acute intermittent porphyria. Although the feces in this disease also have a large amount of fecal porphyrin excretion, the content of protoporphyrin is generally low. In acute attacks, there may also be a large amount of urinary porphyrin, coproporphyrin, ALA and PBG in the urine. The recovery period can be changed to normal.

(two) pathogenesis

Pathological factor

(1) Genetic factors: Porphyrin is an intermediate product of the synthesis process of hemoglobin, myoglobin, catalase, peroxidase and cytochrome in animals. Commonly used in the human body are coproporphyrin I, III, urinary porphyrin I, III, and protoporphyrin IX. In addition, there is a bile precursor, which is a porphyrin precursor, which is excreted in a large amount in the urine of a certain porphyrin patient. The urine color is normal, but after the urine is left in the sun for a few hours, the urine color deepens and turns reddish brown, which is the result of the biliary porphyrin becoming urinary porphyrin. All kinds of porphyrins are colored substances, and under the ultraviolet light of the special filter, they all show red fluorescence, so they can be quantified by fluorescent colorimetry. The coproporphyrin is dissolved in ether and the urinary porphyrin is insoluble, which is convenient for separation. Various porphyrins have different absorption bands in the spectroscopic spectrum.

In the following cases, porphyrin and porphyrin precursors (-aminolevulinic acid, bilirubin) may be increased to cause hematoporphyria.

1 heme synthesis disorder.

2 bulk repressor or manipulation of gene mutations.

3 enzyme defects: such as urinary porphyrinogen I synthetase deficiency, porphyrinogen can not be further cyclized into uroporphyrin, so that porphyrinogen accumulation; or urinary porphyrinogen III co-synthesis enzyme is insufficient, scorpion can not be converted into Urinary porphyrinogen III can only be converted to uroporphyrinogen type I.

(2) Other factors: certain drugs, such as sulfonamide, barbiturate, chlorinated quinine, anesthetics, etc., as well as chemical, poisoning, as well as infection, drinking, fatigue, mental stimulation, menstruation and pregnancy, other diseases such as liver Tumors can induce the onset of the disease.

2. Pathology: The pathological changes are mainly in the liver, and there are a large number of biliary deposits: when there are skin lesions, porphyrins can be seen in addition to sputum. The kidneys also have biliary tract, and bone marrow is rare. The nervous system can have demyelination of nerve fibers, cell swelling and regression. Skin lesions include erythema, blisters, scar formation, and pigmentation.

Hepatic porphyria prevention

The disease is a congenital disease with no special prevention. Prevention is first: avoiding the marriage of close relatives can prevent the occurrence of this disease; patients should strictly stop drinking, and female patients should not give birth to pregnancy.

Hepatic porphyria complications Complications constipation bloating

Patients may have constipation, bloating, vomiting, hypothermia, leukocytosis and increased heart rate.

Hepatic porphyria symptoms Common symptoms Ascites nausea coma jaundice abdominal pain tachycardia reflex disappeared convulsions

Acute intermittent type

It is more common in clinical practice. The First Affiliated Hospital of Zhongshan Medical College has not completely statistics in the past 10 years. In 17 cases of hepatic porphyria, this type accounts for 15 cases, the age of onset is 23 to 58 years old, and 8 cases are 20 to 30 years old. There were 7 males and 8 females. The literature reported that there were very few cases before and after puberty. Abdominal pain and/or neuropsychiatric symptoms were the characteristics of this disease. Because the porphyrins in the body did not increase, there was no photoreceptive skin damage.

Abdominal pain occurs suddenly, varying degrees of severity, usually moderate or severe colic or only heavy pressure, pain is paroxysmal or persistent aggravation, often in the general abdomen, sometimes pain is limited, but no fixed position Abdominal soft, no fixed tenderness point, often accompanied by nausea, vomiting and constipation, sometimes in the abdomen can touch the intestinal loop, intestinal peristalsis sounds normal or weakened, X-ray abdominal plain film see dilated intestinal ring; gastrointestinal meal can be seen Small intestine fistula, in the proximal end of the small intestine fistula can be seen dilated intestinal ring, may have fever, increased white blood cell count, has been reported as misdiagnosed as acute abdomen and laparotomy, sometimes abdominal pain on one side involves the back and to the bladder, outside Genital radiation, and similar to renal colic, abdominal pain episodes last for different lengths, frequency is not necessarily, remission period can be long or short, some patients only after 1 or 2 episodes, that is, not for life, but also every year One or two episodes of seizures are generally considered to be caused by intestinal paralysis due to the imbalance of innervation of the small intestine muscle or the toxic effects of porphyrin precursors due to autonomic neuropathy.

Neuropsychiatric symptoms are various, often occur after abdominal pain or with abdominal pain, and may occur before abdominal pain or alone. Peripheral nerve damage manifests as limb ascending paralysis, paresthesia, paralysis reflexes, and sometimes sputum Positive and achilles tendon reflexes disappeared abnormally, 12 pairs of cranial nerves can be affected, facial nerve spasm is more common, autonomic nerve involvement can be hyperhidrosis, tachycardia, blood pressure wave fluctuations and even upright hypotension, sinus heartbeat Over-speed occurs every time it occurs, disappears when it is relieved, and can be used as an indication of disease activity. Dysphagia, vocal cord paralysis and respiratory center paralysis, hoarseness and even loss of voice are often a precursor to respiratory central paralysis. Hypothalamus Impaired can cause diuretic hormone can not be normal secretion syndrome; and thus cause convulsions, convulsions and even coma, mental symptoms are mainly similar to schizophrenia, snoring and neurasthenia, after the emergence of neuropsychiatric symptoms, the general prognosis is poor, late in the often appear Liver cirrhosis, liver damage, and even severe conditions such as jaundice, ascites, and hepatic encephalopathy.

The urine is red when the attack occurs, such as wine, sometimes the urine is normal when it is just discharged, but it is turned red after being exposed to the sun, acid or heating, which is helpful for the diagnosis of the disease. Urinary excretion - aminolevulinic acid and strontium Increased biliary (normal people discharge 07-32mg of aminolevulinic acid from the urine every day), positive urinary biliary test, is an important laboratory basis for the diagnosis of this disease.

The disease is asymptomatic during the remission period, due to mental stimulation, infection, trauma, drinking, hunger and the use of barbital, chlordiazepoxide, methyl propyl methoxide, sulfa drugs, phenytoin, griseofulvin Estrogen and other drugs are induced; during the episode, the disease may be aggravated due to the above factors, and the seizure of some female patients may be related to menstruation and pregnancy.

Other patients have a latent and asymptomatic course, only urinary excretion - aminolevulinic acid, an increase in biliary tract, known as latent type, but under the above-mentioned various predisposing factors, sometimes can also cause acute attacks.

2. Delayed skin type

The incidence is mostly in middle-aged, males are more common, the skin may have eczema-like, urticaria-like, summer pruritic rash and polymorphic erythema, which occurs more often after exposure. When the sun is sufficient, the skin of the exposed parts of the body is often slightly After trauma or pressure, erythema with blisters appears. After the blister oozes, smashes, scars and forms scars, chronic skin damage can be hairy, pigmented, miliary rash and similar scleroderma, dermatitis, There are varying degrees of liver damage, caused by porphyrin deposition in the liver, some patients with alcoholic cirrhosis, others with hepatic adenoma, drinking, using estrogen or iron, and contact with BHC Etc., often the cause of the onset, when the attack, urine excretion of urinary porphyrin I, - amino keto valeric acid and bilirubin is normal, when relieved, urine urinary porphyrin I decreased, while fecal excretion of porphyrin increased.

3. Mixed or mutated

The age of onset is mostly between 10 and 30 years old. The clinical manifestations are characterized by the above two types. This type is a dominant hereditary hepatic porphyria in middle-aged white Africans. It can be traced back to a white family immigrating from the Netherlands. In addition to abdominal symptoms and neurological symptoms in adulthood, there are skin-sensitive lesions, skin sensitive to light, occasional herpes, skin lesions are intermittent, sometimes the only clinical symptoms of this disease, some patients have acute attacks Abdominal pain and paralysis, mild mechanical skin trauma, sometimes induced skin lesions, women with more obvious skin lesions during pregnancy, in the intermittent period of barbiturates, chlorinated quinine, alcohol and anesthetics can induce acute attacks, should be considered Medication contraindications, severe cases of abdominal symptoms, neurological symptoms and liver damage symptoms and acute intermittent type, porphyrin metabolism disorder is characterized by intermittent or incubation period, urinary porphyrin and porphyrin precursors - aminolevulinic acid and guanidine The biliary is negative, and a large amount of fecal porphyrin and protoporphyrin are excreted in the feces. In the acute attack period, fecal porphyrin and protoporphyrin are excreted in the feces, and urinary-amino-B Propionic acid and porphyrin urobilinogen also increased significantly, it is the diagnosis.

4. Hereditary fecal porphyrin type

Can be seen at any age, men and women are equal, have a clear family history, the disease is latent and asymptomatic, only fecal excretion of fecal porphyrin, but in the barbital, methyl propyl amide (Sirmant), phenytoin and other drugs induced Acute intermittent clinical manifestations may occur, skin lesions are rare, and individual patients may develop photoreceptive skin lesions. Its biochemical diagnosis is characterized by a large amount of fecal porphyrin III excretion in feces, but no protoporphyrin, urinary coproporphyrin III The type may not increase, but in the acute episode, the content of fecal porphyrin III in the urine and its precursors, bilirubin and -aminolevulinic acid are increased, and of course, fecal porphyrin III is more in the feces.

Examination of hepatic porphyria

Acute intermittent type

The urine color just solved is mostly normal, but if the urine is placed in direct sunlight, the urine gradually turns dark red or even black, which is the conversion of PBG into red urinary porphyrin and sputum under the action of light. As a result, the resulting urinary porphyrin has a special spectrum, which emits red fluorescence under ultraviolet irradiation. If the urine becomes strongly acidic, it boils for 30 minutes, and the urine color quickly turns dark red or brownish red, dimethylaminobenzaldehyde. The test (Watson-Schwartz test) is a simple and reliable method for examining PBG. PBG reacts with dimethylaminobenzaldehyde (Ehrlich's aldehyde reagent) to become deep red, and urinary bile or sputum and this reagent are also produced. Red, but after the two substances are shaken with chloroform or butanol, the red is removed by this solvent, and the red color of PBG is still in the water layer. When the disease is acute, this test is often strongly positive; The period is usually also positive, but sometimes it can be negative; in the case of recessive cases, the result of this test is weakly positive or negative.

The most reliable diagnosis is based on the determination of ALA and PBG in urine by chromatography. Especially in the intermittent and recessive cases, the PBG excretion is about 50-200 mg/d in the acute attack period (normal range is 0~). 4mg/d), ALA excretion is about 20 ~ 100mg / d (normal range is 0 ~ 7mg / d), ALA and PBG measured values often decrease with the improvement of clinical symptoms, for epileptic cases, if in clinical work A positive result of the dimethylaminobenzaldehyde test can establish a diagnosis.

2. Delayed skin type

The excretion of ALA and PBG in urine is not increased. The fecal porphyrin in feces is often increased. The original porphyrin is normal or moderately increased. Most patients have no anemia. A few patients may have mild erythrocytosis. Because patients often have liver disease, Urinary bile may be positive, serum transaminase may be increased, and excretion of sodium sulfonium bromide is often lower than normal.

3. Mixed or variant

The most important laboratory findings are the large amount of coproporphyrin and protoporphyrin in the bile and feces during the onset and remission period, even in the case of mild or in childhood, in the case of acute attacks, in the urine. Both ALA and PBG increased significantly, and urinary porphyrin and coproporphyrin were also significantly increased.

4. Hereditary fecal porphyrin type

Although the feces in this disease also have a large amount of fecal porphyrin excretion, the content of protoporphyrin is generally low. In acute attacks, there may be a large amount of urinary porphyrin, fecal porphyrin, ALA and PBG in the urine. It becomes normal.

You can choose to do B-ultrasound, X-ray, electrocardiogram, EEG, CT and other checks.

Diagnosis and identification of hepatic porphyria

Diagnostic criteria

Acute intermittent type

The most important basis for diagnosing the disease is the presence of large amounts of ALA and PBG in the urine.

The disease is relatively rare, easy to be ignored, the cause of unexplained abdominal pain must consider the possibility of acute intermittent porphyria, unexplained neurological disorders, especially peripheral nerve symptoms, local muscle weakness, relaxation sputum, etc., neuropsychiatric or The psychiatric illness is aggravated by taking barbiturate, or with menstrual cramps, or when taking female hormones or birth control pills, the authors suspect the possibility of porphyria.

2. Delayed skin type

The main finding is that there are more urinary porphyrins and coproporphyrins in the urine, and the urine is red.

3. Mixed or variant

Mainly manifested as dermal abrasions, superficial erosion and blisters after minor skin damage.

4. Hereditary fecal porphyrin type

Some patients have photoreceptive skin lesions, and their clinical manifestations are similar to those of acute intermittent porphyria.

Differential diagnosis

1. When the disease is abdominal pain, it should be differentiated from acute abdomen.

2. When there are neuropsychiatric symptoms, it should be differentiated from pellagra, scleroderma and dermatomyositis.

3. When the disease occurs urinary bilirubin positive, it should be associated with lead, gold, arsenic, alcohol, benzene, carbon tetrachloride poisoning, and aplastic anemia, substantial liver disease, connective tissue disease, Hodgkin's disease, leukemia Identification of symptomatic porphyrin urine caused by et al.

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