ALAD Porphyria (ADP) is a very rare genetic metabolic disease characterized by almost complete deficiency of the enzyme delta-aminolevulinic acid (ALA) dehydratase. In ADP, the gene responsible is ALAD which produces the enzyme δ-aminolevulinic acid dehydratase. Deficiency of this enzyme leads to the accumulation of the toxic porphyrin precursor ALA, which can potentially result in a variety of symptoms. Symptoms vary from one person to another, but usually come from the neurological and gastrointestinal systems. This disease is inherited as an autosomal recessive disorder. ADP is more severe than the other acute Porphyrias and can present in childhood. Only ~10 cases have been reported worldwide and all reported cases have been males, in contrast to the other acute Porphyrias where more women are symptomatic.
ADP is caused by a deficiency of the enzyme δ-aminolevulinic acid dehydratase (ALAD).
The mutation is in the ALAD gene, and the disease is inherited as an autosomal recessive disorder, meaning one copy of the abnormal gene is inherited from each parent. Mutations of the ALAD gene result in deficient levels of porphobilinogen in the body, with an accumulation of ALA, which causes the symptoms associated with ALAD Porphyria.
A variety of different triggers have been identified that can precipitate an acute attack in individuals with ALAD Porphyria. These triggers include alcohol, certain drugs, physical and psychological stress, infection, fasting (reduced caloric intake) and dehydration. The use of estrogen or progesterone is also suspected of triggering an acute attack.
Individuals with ALAD Porphyria may have bouts where symptoms are intense, which are referred to as neurovisceral or acute attacks. An attack may last for several weeks. During an attack, affected individuals may experience severe abdominal cramping or pain accompanied by vomiting and constipation. During infancy, gastrointestinal abnormalities may cause an affected child to fail to grow and gain weight as expected.
Several other neurological symptoms can occur during an acute attack due to problems with the nerves outside the central nervous system (peripheral neuropathy), resulting in numbness or tingling in the hands and feet, burning pain, sensitivity to touch, and a lack of coordination. In severe cases, the motor nerves are involved, resulting in loss or partial impairment of the ability to use voluntary muscles. ALAD Porphyria can also be associated with psychological changes during an acute attack. In severe cases, loss of contact from reality (psychosis) has been reported.
Additional symptoms that occur during acute attacks include a rapid heartbeat (tachycardia), high blood pressure (hypertension), seizures, and breathing (respiratory) impairment.
Biochemical testing means looking for “biomarkers” in the blood or urine. To diagnose ADP, measurements of the biomarkers porphobilinogen (PBG), aminolevulinic acid (ALA), and total porphyrins in the urine should be done. Also porphyrins in the blood should be measured. The level of PBG in the body can vary so the best time to take samples is during an acute attack (e.g. when someone is having abdominal pain, etc). Slight elevations in porphyrins are not diagnostic of ADP; the levels need to be very high.
DNA testing to identify the specific mutation in an individual’s Porphyria-causing gene is the most specific and sensitive test to confirm the diagnosis of a specific Porphyria. Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (ALA and PBG) and/or enzyme assays).
For the acute Porphyrias, hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or intravenous administration of hemin (Panhematin®). Attacks can be prevented in many cases by avoiding harmful drugs (Safe/Unsafe Drug Database) and adverse dietary practices (Diet and Nutrition).
The treatment of ALAD Porphyria is directed toward the specific symptoms that are present in each individual. Because there have been so few cases of ALAD Porphyria, there is only limited information on treatment for the disorder.
Avoidance of triggering factors such as alcohol, certain drugs, fasting, and low carbohydrate diets is recommended for affected individuals. The specific drugs that may need to be avoided in one person can differ from the drugs that need to be avoided in another.
Two standard treatments for acute Porphyrias in general are intravenous infusions of hemin and supplementation with glucose. However, these therapies have not been universally effective in treating individuals with ALAD Porphyria.
Hemin is an orphan drug that has been approved by the Food and Drug Administration (FDA) for the treatment of acute Porphyria. The drug known as Panhematin® (hemin for injection) is usually given to treat an acute attack.
Wearing a Medic Alert bracelet or the use of a wallet card is advisable in individuals who have ADP.