OVERVIEW
Porphyrias are caused by enzyme defects that result in disorders of porphyrin metabolism, causing toxic reactions. Depending on the site of the disorder of porphyrin metabolism, porphyrias are categorized as erythropoietic porphyrias and hepatic porphyrias. Hepatic porphyrias are divided into four types: acute intermittent porphyrias, delayed cutaneous porphyrias, variegated porphyrias, and hereditary fecal porphyrias. Hepatic porphyrias are mainly characterized by paroxysmal abdominal pain, mostly severe colic, as well as sensory disturbances, drooping of the hands and feet, extreme weakness, and quadriplegia.
Etiology
This disease is an autosomal dominant disorder. In the process of porphyrin metabolism and synthesis of bilirubin, due to the lack of porphobilinogen synthase, porphobilinogen can not be metabolized and accumulated in the body, so that the synthesis of bilirubin is reduced, and the activity of α-amino ketoglutarate synthetase can be increased through the feedback effect, and as a result, the production of α-amino ketoglutarate and porphobilinogen increases in vivo, and the increase in their toxicity through the direct or indirect mechanism in the neurotransmitter function, which in turn causes this disease. The disease is autosomal dominant. The disease is inherited as an autosomal dominant disorder. In the process of porphyrin metabolism and synthesis of bilirubin, due to the lack of porphobilinogen synthase enzyme, porphobilinogen can not be metabolized and accumulated in the body, so that the synthesis of bilirubin decreases, and the activity of α-amino ketoglutarate synthetase can be increased through the feedback effect, and as a result, the α-amino ketoglutarate and porphobilinogen increase in vivo, and the increase in the production of porphyria and porphobilinogen through the direct or indirect mechanism of the neurotransmitter functions in toxicity, which in turn cause the disease The disease can be triggered by the onset of the disease.
Symptoms
The clinical picture of the disease varies widely and is characterized by intermittent episodes of small abdominal cramps and neuropsychiatric symptoms. It can be triggered by the administration of barbiturates, sulfonamides, or stress. The abdominal manifestations are severe colic, accompanied by constipation, nausea and vomiting, similar to the manifestations of acute abdomen, but the abdominal pain does not have a fixed site, and there is no abdominal rebound pain and muscle tension. Peripheral motor nerve disorders include limb weakness, mild paralysis, and even flaccid paralysis. Mental symptoms may include depression, confusion, and hallucinations. Symptoms often recur in acute episodes, which can last from a few days to a dozen days. In addition, there may be manifestations of vegetative dysfunction, such as tachycardia, hypertension, and urinary retention. Due to the increased excretion of δ-amino ketoglutarate and porphobilinogen from the kidneys, the patient’s urine can change to red or tea color when exposed to sunlight, which is a very important feature of this disease.
Examination
Laboratory tests show an increase in the excretion of uroporphyrin and fecal porphyrin in the 24-hour urine, and an increase in porphobilinogen and delta-aminolevulinic acid in the 24-hour urine. Measurement of blood erythrocyte uroporphyrinogen synthase deficiency (normal >30 mmol porphyrin/1 ml erythrocyte-h).
Diagnosis
The complexity of the disease, the variability of symptoms with individual differences, and the lack of specific indications make the clinical diagnosis of the disease difficult. Knowledge of the following features may help reduce misdiagnosis.
1. Multiplicity and specificity of abdominal pain: abdominal pain is almost inevitable in this disease (98%), and most of the patients often consult the doctor and complain about it. It is characterized by sudden onset, continuous aggravation, no time to rest, long time to wait. The nature of the pain is mostly colic, distension, attack and punch pain, less cut and needle-like. Most of them are not accompanied by fever or only low fever; blood and urine routine tests have no specific changes. There may be accelerated heart rate and elevated blood pressure (>20%).
2. Mostly accompanied by nausea, vomiting, varying in severity, can be alleviated with the relief of abdominal pain, occasionally vomiting roundworms or coffee-like substances.
3. Lingering, stubborn constipation, mostly recurring, days to weeks, difficult to self-resolve, often need multiple enemas. It is easy to be misdiagnosed as intestinal obstruction, and seldom has other signs of intestinal obstruction, dehydration, electrolyte disorders, and so on.
4. The grotesque nature of mental variability: patients are often accompanied by neurasthenia, neurosis, mania or depression, hysteria-like episodes, etc., characterized by often sudden, unexplained, mostly accompanied by abdominal pain or limb abnormalities. Mental induction, suggestion therapy, acupuncture and ordinary tranquilizers are difficult to work, and a large amount of winter eye spirit can relieve, but it is not always true.
5. Diversity of neurological signs: (1) Abnormal self-sensation of the limbs, with bizarre complaints, such as sudden, localized or non-localized skin pain, itching, numbness, cold and hot at first sight; or spasms, convulsions, and upward flaccid paralysis. (2) Epileptiform seizure, not only its tonic paroxysmal twinning seizure is similar to grand mal seizure, but also its episodic muscle anisocoria and limited dysfunction are very similar to simple partial seizure of epilepsy. (3) Coma is a dangerous sign of the disease and has a poor prognosis.
6. Connection and disjunction between symptoms: There is a close correlation and physiological-pathological consistency among the three major syndromes of typical hepatic hemolymphadenopathy: abdominal, psychoneurological and skin damages. Abdominal pain, nausea and vomiting, constipation, psychiatric changes, neurological disorders, skin damages, etc., are more often associated with the occurrence of the disease, and rarely occur singly. Other diseases rarely have such a connection. It is difficult to make an organic, not far-fetched, connection and exact physiological and pathological explanation of the above symptoms with a particular disease. This kind of association and disconnection between symptoms is an important clue to exclude other diseases and confirm the diagnosis of this disease.
7. urine color, porphobilinogen specificity: most patients after the onset of the urine color is dark tea, coffee or wine color, or urine color is normal and after exposure to sunlight, heating or acid red. The definitive diagnosis is a postictal test for urinary porphobilinogen and porphobilinogen, with at least the former being positive. However, a negative porphobilinogen test at the beginning of an attack or during the intermittent period should not be used to dismiss the diagnosis. Symptomatic porphyrias should also be excluded.
Differential diagnosis
The key to diagnosing this disease is to be vigilant. Because of the relative rarity of the disease and the absence of specific symptoms, it is often misdiagnosed, with a reported misdiagnosis rate of 73%. When abdominal pain is present, it should be differentiated from acute abdominal conditions such as cholelithiasis, ulcer disease and many other diseases. Neuropsychiatric symptoms should be differentiated from pellagra, scleroderma and dermatomyositis. When the disease is positive for urobilinogen, it should be distinguished from lead, gold, arsenic, alcohol, benzene, carbon tetrachloride poisoning, as well as symptomatic porphyrinuria caused by aplastic anemia, parenchymal liver disease, connective tissue disease, Hodgkin’s disease, and leukemia.
Treatment
1. Symptomatic treatment, prevention of recurrence, reduction of skin damage
Avoid sun exposure and trauma, wear protective clothing. Take oral β-carotene or riboflavin, or oral adiponectin every other day.
2. Try to avoid triggers
Such as overwork, mental stimulation and hunger, infection, prohibition of alcohol, etc.
3. Hormone therapy
In a few cases where the acute attack is obviously related to the menstrual cycle, the application of androgens, estrogens or oral female contraceptives are effective, but persistent hypertension may occur, and the mechanism is unknown. Prednisone (prednisone) is used in patients with postural hypotension.
4. Acute phase
To relieve symptoms quickly, give glucose 400g/d. If the patient can not eat, can be given 10% or 25% glucose solution intravenous drip, 10-20g per hour; if necessary, add insulin. Pay attention to correct water and electrolyte disorders.
Prevention
1. Reduce skin damage
Avoid sunlight exposure and trauma, wear protective clothing.
2. Avoid triggers as much as possible
Such as overwork, mental stimulation and hunger, infection, prohibition of alcohol as well as etc..
3. Careful use of medication
Patients should use barbiturates, meprobamate (mirtazapine), sulfonamides, and phenytoin sodium, ashwagandha and estrogen with strict caution to prevent triggering or exacerbating the disease.
Prognosis
Prompt and rational treatment of acute attacks of the disease can significantly reduce the mortality rate. With age, the disease tends to reduce, and the prognosis is good.