Information on the following diseases can be found in the Related Disorders section of this report:

• Porphyrias
• Acute Intermittent Porphyria
• Congenital Erythropoietic Porphyria (CEP)
• Porphyria Cutanea Tarda (PCT)
• Hereditary Coproporphyria (HCP)
• Variegate Porphyria (VP)
• Erythropoietic Protoporphyria (EPP)

ALA-D porphyria is a recently-described form of acute porphyria whose symptoms are very similar to those of Acute Intermittent Porphyria (AIP). This is a deficiency of the enzyme delta-aminolevulinic acid dehydratase (ALA-D) and there is increased excretion of ALA in the urine of patients with this type of porphyria.

Symptoms of ALA-D Porphyria generally arise from effects on the nervous system and/or the skin. Sometimes, the cause of the nervous system symptoms is not clear, and proper diagnosis is delayed. Skin manifestations can include burning, blistering and scarring of sun-exposed areas.

Porphyria Cutanea Tarda is the only type of porphyria that can be either acquired or inherited. All other types of Porphyria are caused by genetic factors. Environmental factors such as drugs, chemicals, diet and sun exposure can, depending on the type of the disorder, greatly influence the severity of symptoms.

The terms "porphyrin" and "porphyria" are derived from the Greek word "porphyrus," meaning purple. Urine from some porphyria patients may be reddish in color due to the presence of excess porphyrins and related substances, and the urine may darken after being exposed to the light.

Many individuals who inherit the gene for ALA-D porphyria never develop symptoms. In those who do display symptoms, the disease may become manifest after puberty, and more commonly does so in women than in men. Abdominal pain, which can be severe, is the most common symptom. Other characteristics may include nausea, vomiting, constipation, and pain in the back, arms and legs; muscle weakness, rapid heart rate, increased blood pressure, confusion, hallucinations or seizures may also be present. Sometimes the level of salt (sodium chloride) in the blood decreases markedly during attacks and contributes to some of these symptoms.

Because this disease can mimic a host of other more common conditions, its presence is often not suspected. On the other hand, the diagnosis of this and other types of porphyria is sometimes made incorrectly in patients who do not have porphyria, particularly if improper laboratory tests are carried out. The finding of increased levels of delta-aminolevulinic acid (ALA) in urine establishes that one of the "acute" porphyrias is present. If ALA-D is deficient (approximately one-half normal) in red blood cells, then the diagnosis of ALA-D is established. However, the latter test should not be relied upon by itself to exclude ALA-D in a patient, because the result can be falsely normal or equivocal in some ALA-D patients. The red blood cell test can be extremely useful in identifying other family members who have inherited ALA-D. It should also be remembered that ALA-D patients can develop other illnesses, and symptoms may not always be due to porphyria.

When a patient is diagnosed as having ALA-D, relatives should be examined as well. Latent cases so identified can then avoid agents known to cause attacks.

ALA-D porphyria is inherited as an autosomal recessive trait. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal. The risk is the same for each pregnancy.

Environmental factors that can precipitate attacks of ALA-D porphyria may include drugs, chemicals, diet and sun exposure. Depending on the type of porphyria, these factors can greatly influence the severity of symptoms.

Because all porphyrias are uncommon, it is very unlikely that more than one type will occur in the same family, or that someone with one type of porphyria will go on to develop another.

ALA-D Porphyria affects a very small segment of the world population. Less than one per one hundred thousand cases occurs, usually in people of Scandinavian, Anglo-Saxon, or German ancestry. It is extremely rare in Americans of African descent. Young or middle-aged adult women are more frequently affected.

The Porphyrias are a group of related disorders. For more information on each of the following types of the disease, choose "porphyria" as your search term in the Rare Disease Database.

Acute Intermittent Porphyria is a hereditary, usually asymptomatic disorder (latent). It may be provoked into active disease by the administration of certain drugs, notably barbiturates, sulfonamides, and estrogenic compounds.

Congenital Erythropoietic Porphyria (CEP) is a hereditary disorder due to an inborn error of metabolism, and manifested in infancy. Faulty conversion of the enzyme PBG to uroporphyrinogen in erythroid cells of bone marrow, and red blood cells leads to of this type of Porphyria. Increased porphyrins also may be found in plasma, urine, feces, teeth and bones.

Porphyria Cutanea Tarda (PCT) can be either an acquired or inherited type of Porphyria. It may become acute due to exposure to chronic alcoholism, barbiturates or other chemicals, cirrhosis of the liver, or a hepatic tumor. It may also stem from a nutritional disorder.

Hereditary Coproporphyria (HCP) is a latent type of Porphyria with attacks usually precipitated by exposure to drugs such as barbiturates, tranquilizers, anticonvulsants, and estrogens.

Variegate Porphyria (VP) is a hereditary type of Porphyria due to an inborn error of metabolism. Precipitating or aggravating factors may include exposure to barbiturates, sulfonamides, general anesthetics, excessive amounts of ethanol, and estrogens.

Erythropoietic Protoporphyria (EPP) is a hereditary type of Porphyria marked by an accumulation of protoporphyrin in the bone marrow, red blood cells and sometimes the liver. Excess protoporphyrin is excreted by the liver into the bile, which in turn enters the intestine and is excreted in the feces. There are no urinary abnormalities. The diagnosis is established by finding increased protoporphyrin in red blood cells, plasma and feces.

ALA-D Porphyria should be treated much the same as Acute Intermittent Porphyria (AIP). The orphan drug Panhematin (hemin for injection), formerly known as Hematin, is very potent in suppressing acute attacks of the disease. It is usually given only after a trial of glucose therapy and should be administered by a physician experienced in the treatment of the porphyrias in a hospital setting. Panhematin is manufactured by Abbott Laboratories.

Many types of drugs such as aspirin and certain antibiotics are believed to be safe in patients with some types of porphyria. Recommendations about drugs for certain types of the disorder are based on experience with the porphyria patients in whom attacks have been caused by drugs and by tests in animals. Since many commonly used drugs have not been tested, they should be avoided if at all possible. If a question of drug safety arises, a physician or medical center specializing in porphyria should be contacted. A list of these institutions may be procured from the American Porphyria Foundation (see Resources).

ALA-D Porphyria is particularly dangerous if the proper diagnosis has not been made, and if drugs which aggravate this disorder are administered. The prognosis is usually good if the disease is recognized before severe nerve damage has occurred and if treatment and preventive measures are begun. Although symptoms usually resolve after an attack, some patients may develop chronic pain. Nerve damage and associated muscle weakness can improve over a period of months after a severe attack. Mental symptoms may occur during attacks, but are usually not chronic.

If the patient is taking drugs, (including barbiturates, sulfonamides, tranquilizers or sedatives, antiseizure drugs, birth control pills or alcohol, etc.), they should be stopped under a physician's supervision.

Attacks are often precipitated by low intake of carbohydrates in an attempt to lose weight, thus dietary counseling can be very important. Premenstrual attacks often resolve quickly with the onset of menstruation; hormone manipulations may prevent occurrences of such attacks.

ALA-D patients prone to attacks should eat a normal or high carbohydrate diet and should not greatly restrict their intake of carbohydrates and calories, even for short periods of time. If weight loss is desired, it is advisable to consult a physician who may then request that a dietitian estimate an individual's normal caloric intake (this varies greatly from one person to another). Then it may be appropriate to prescribe a diet which is approximately ten percent below the normal level of calories for the patient. This usually will not cause an attack of porphyria.

Pregnancy is tolerated much better than was formerly believed. Offspring have a fifty percent chance of inheriting the gene for ALA-D, but the great majority of those that will remain "latent" for all or most of their life times. If diagnosed early, the minority that eventually have symptoms will usually benefit from treatment. Given these considerations, most patients or individuals with "latent" porphyria usually have few reservations about family planning, For those who do, genetic counseling may be indicated.

Wearing a Medic Alert bracelet is advisable in patients who have had attacks, but is probably not warranted in most latent cases.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

American Porphyria Foundation brochure, "Common Questions About Porphyria."

Hedger RW, Wehrmacher WH, French AV. Porphyria syndrome associated with diabetic nephrosclerosis and erythropoietin. Compr Ther. 2006 Fall;32(3):163-71.

Méndez M, Parera V, Enríquez de Salamanca R, Batlle A. Amiodarone is a pharmacologically safe drug for porphyrias. Gen Pharmacol. 1999 Feb;32(2):259-63.

Princ FG, Juknat AA, Amitrano AA, Batlle A. Effect of reactive oxygen species promoted by delta-aminolevulinic acid on porphyrin biosynthesis and glucose uptake in rat cerebellum. Gen Pharmacol. 1998 Jul;31(1):143-8.

Mercelis R, Hassoun A, Verstraeten L, De Bock R, Martin JJ. Porphyric neuropathy and hereditary delta-aminolevulinic acid dehydratase deficiency in an adult. J Neurol Sci. 1990 Jan;95(1):39-47.