MEASUREMENT OF HMB-SYNTHASE IN RBC, OR BETTER, THE DETECTION OF THE FAMILYS HMB-SYNTHASE MUTATION, WILL DIAGNOSE ASYMPTOMATIC FAMILY MEMBERS. THE PRENATAL DIAGNOSIS OF A FETUS AT RISK CAN BE MADE WITH CULTURED AMNIOTIC CELLS OR CHORIONIC VILLI.
ENVIRONMENTAL TRIGGERS, INFECTION, SURGERY & LOW CALORIC DIET ARE IIMPORTANT IN MANY ATTACKS OF PORPHYRIA. GENETIC CARRIERS WHO AVOID THESE MAY NEVER EXPERIENCE SYMPTOMS.
RISK FACTORS
β’ Multiple precipitating factors, especially AIP, VP, HCP
β’ Drugs (e.g., barbiturates and sulfas in AIP)
β’ Estrogens, especially oral contraceptives
β’ Steroids
β’ Liver disease
β’ Menstrual cycles
β’ Infection
β’ Fasting
β’ Heavy alcohol use
β’ Hexachlorobenzene exposure
MEDICAL TREATMENT :
Medical Care:
The treatment goal for acute attacks of porphyria is to decrease heme synthesis and reduce the production of porphyrin precursors.
High doses of glucose (400 g/d) can inhibit heme synthesis and are useful for treatment of mild attacks.
People experiencing severe attacks, especially those with severe neurologic symptoms, should be treated with hematin in a dose of 4 mg/kg/d for 4 days.
Pain control is best achieved with narcotics. Laxatives and stool softeners should be administered with the narcotics to avert exacerbating existing constipation.
Treat seizures with Neurontin. Most classic antiseizure medicines can lead to acute porphyria attacks.
Diet:
The patient should receive a high-carbohydrate diet during the attack. If the patient is unable to eat, intravenous glucose should be administered.
Between attacks, eating a balanced diet is more important than eating one rich in glucose.
DRUG TT : I.V. HEME IS MORE EFFECTIVE THAN I.V. GLUCOSE & RESPONSE TO HEME THERAPY IS REDUCED IF DELAYED. 3 - 4 MG OF HEME, IN THE FORM OF HEMATIN, HEME ALBUMIN, HEME ARGINATE MAY BE INFUSED DAILY FOR 4 DAYS
ALTERNATIVE DRUGS
. PCT
. chloroquine 125 mg twice weekly, or hydroxychloroquine 250 mg tid, in conjunction with phlebotomy
. With hepatitis C virus - interferon beneficial for both
. thalidomide being studied
. CEP and PP. In vitro gene therapy has been successful
. AIP
. LHRH analogues being studied
. antioxidants ineffective
. Menstruating women - hematin premenstrual; cycle suppressors, e.g., luteinizing hormone releasing hormone (LHRH) analogues
. Autonomic manifestations - beta blockers
. Other symptoms - treat symptomatically
PATIENT MONITORING Individualized
PREVENTION/AVOIDANCE
. Avoid precipitating drugs
. Alcohol
. Barbiturates
. Carbamazepine
. Chlorpropamide
. Danazol
. Ergots
. Estrogens and progestins
. Ethchlorvynol
. Glutethimide
. Griseofulvin
. Mephenytoin
. Meprobamate
. Methotrexate
. Methyprylon
. Metoclopramide
. Phenytoin
. Pyrazolones
. Succinimides
. Sulfonamide antibiotics
. Valproic acid
. Eat an adequate diet with high carbohydrate intake
POSSIBLE COMPLICATIONS
. Neurologic:
. Essentially anything
. Includes sensory and motor systems
. Includes autonomic nervous system
. May include seizures
. May lead to quadriplegia and/or respiratory paralysis with death
. Psychiatric:
. Essentially anything
. Psychosis most common
. Visual hallucinations common
. Disorientation frequent
. Chronic depression frequent
. Dermatologic:
. Photosensitivity
. Scrapes, ulcerations, blisters with minimal trauma
. Hyperpigmentation, especially hands and face
. Scarring frequent
. Facial hypertrichosis
. CEP - mutilating, with hemolysis, erythrodontia, splenomegaly
. PP - occasional hepatic disease, including hepatic failure
EXPECTED COURSE/PROGNOSIS
. In all porphyrias:
. Patients who are asymptomatic or minimally symptomatic
- unaffected longevity
. Patients who are more symptomatic - treatable and do well
. Neurologic complications (e.g., peripheral neuropathy, neurosis or hemiplegia), at times permanent
. In AIP
. Acute attacks have 25% mortality
. Increased risk of hepatocellular carcinoma
. Acquired PCT
. HIV
. Hepatitis C virus
. Hepatic malignancies