What are the other Names for the Condition? (Also known as/Synonyms)

• Amino Levulinic Acid Dehydratase Deficiency (ALAD) Disorder
• Doss Porphyria
• Plumboporphyria

What is Aminolevulinic Acid Dehydratase Deficiency Porphyria? (Definition/Background Information)

• Porphyrias are disorders resulting from excess porphyrin buildup in the liver and bone marrow. Manufacturing hemoglobin and related proteins (heme synthesis) involves a class of molecules called porphyrins. Porphyrias are either inherited or acquired, and are described as acute, chronic, and cutaneous
• Aminolevulinic Acid Dehydratase Deficiency Porphyria (ALAD Porphyria) is an extremely rare congenital condition affecting heme metabolism, usually having  onset in childhood. It is generally described as a neuropsychiatric condition. Unlike many other porphyria types, signs and symptoms involving the skin are not noted
• Aminolevulinic Acid Dehydratase Deficiency Porphyria is an acute form of porphyria that is typically inherited in an autosomal recessive manner, due to certain gene mutations which cause a defect in heme production in the bone marrow and liver. ALAD Porphyria is termed as a hepatic porphyria, meaning that the porphyrin compounds accumulate in the liver
• The disorder is characterized by neurological and psychiatric symptoms that include muscle pain, weakness, confusion, and hallucinations. A healthcare provider typically diagnoses this genetic disorder by testing porphyrin levels in urine and blood samples, along-with symptom assessment
• The treatment for Aminolevulinic Acid Dehydratase Deficiency Porphyria involves symptomatic treatment, and this includes administering intravenous heme and antipsychotic medications
• The prognosis of Aminolevulinic Acid Dehydratase Deficiency Porphyria is determined by the severity of symptoms and whether any complications have developed in the individual

Who gets Aminolevulinic Acid Dehydratase Deficiency Porphyria? (Age and Sex Distribution)

• Aminolevulinic Acid Dehydratase Deficiency Porphyria is an extremely rare genetic condition. Globally, only about 10 cases have been recorded in the medical literature
• The symptoms of the condition are often onset in young children (including in infants); in some the onset may occur during adulthood
• Due to the rarity of ALAD Porphyria, the distribution pattern and demographic features of the condition are not known yet

What are the Risk Factors for Aminolevulinic Acid Dehydratase Deficiency Porphyria? (Predisposing Factors)

• A family history of Aminolevulinic Acid Dehydratase Deficiency Porphyria increases the risk of a newborn being diagnosed with the condition, since ALAD Porphyria is an inherited disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Aminolevulinic Acid Dehydratase Deficiency Porphyria? (Etiology)

Aminolevulinic Acid Dehydratase Deficiency Porphyria is caused by certain gene mutations (involving the ALAD gene), which is involved in the production of “heme”.

• Heme is a critical component of iron-containing proteins called hemoproteins. Hemoglobin is one such protein, which is the oxygen carrier in blood. Red blood cells, bone marrow, and liver have the most heme protein in them
• The mutations are inherited in an autosomal recessive manner. Mutations in the defective gene affects porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of porphyrins in the body
• This mutation affects the function of the specific enzyme aminolevulinic acid dehydratase (ALAD, also called porphobilinogen synthase enzyme), in the red blood cells and liver. The level of ALAD enzyme, which is important for the multistep process of generating heme, is reduced to a great extent, thereby affecting heme metabolism process
• Aminolevulinic Acid Dehydratase Deficiency Porphyria is described as a type of porphyria affecting the liver (hepatic porphyria), because porphyrin compounds collect in the liver in excessive amounts

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Aminolevulinic Acid Dehydratase Deficiency Porphyria?

The signs and symptoms of Aminolevulinic Acid Dehydratase Deficiency Porphyria may vary from one individual to another, and may be mild or severe. The signs and symptoms of ALAD Porphyria may include:

• Abdominal pain, persistent and cramping
• Neurological signs and symptoms that may include:
  • Peripheral neuropathy
  • Muscular pain and weak muscles; lethargy
  • If the respiratory muscles are affected,  it can result in breathing difficulties
  • Seizures in some cases
• Psychiatric signs and symptoms that may include:
  • Change in sensation
  • Confusion
  • Hallucinating
• Since liver involvement is present in ALAD Porphyria, yellowing of skin and sclera (the whites of eyes) may be observed

How is Aminolevulinic Acid Dehydratase Deficiency Porphyria Diagnosed?

The diagnosis of Aminolevulinic Acid Dehydratase Deficiency Porphyria is made by the following tools:

• A complete physical examination and an assessment of symptoms
• An evaluation of the affected individual’s full medical history
• Measurement of the porphyrin levels in blood, urine, or feces: Accumulated porphyrins are excreted through urine, and urinary secretion of ALA is high
• Measurement of aminolevulinic acid dehydratase enzyme activity

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Aminolevulinic Acid Dehydratase Deficiency Porphyria?

The potential complications of Aminolevulinic Acid Dehydratase Deficiency Porphyria may include:

• Severe pain and emotional stress
• Anemia and related conditions, due to low levels of oxygen transport
• Increased heart rate and increased blood pressure may be the outcome of autonomic nervous system being affected
• If the neuroendocrine region of brain is affected, it can lead to hyponatremia and hypomagnesemia (low sodium and magnesium levels in blood respectively), resulting in additional complications

How is Aminolevulinic Acid Dehydratase Deficiency Porphyria Treated?

A symptomatic treatment of Aminolevulinic Acid Dehydratase Deficiency Porphyria may include the following treatment measures:

• When the first signs of disease are recognized, the individual is given oral/intravenous glucose (called glucose loading) and a carbohydrate-rich diet
• Medications to control severity of the acute attacks
• Large dose and strong painkillers (narcotic analgesics or opiates) may be given for severe pain
• Antipsychotic medication (chlorpromazine) to treat some of the neurological symptoms, antidepressants for depression
• Beta-blockers, such as propranolol, for cardiovascular conditions (such as hypertension and tachycardia)
• Anti-seizure medications (such as gabapentin) for seizure
• Blood disorder medications (intravenous heme or hematin) may be used  
• Blood transfusions, based on the severity of anemia
• A splenectomy (removal of the spleen) to alleviate bleeding and worsening anemia (due to spleen enlargement)
• Bone marrow transplant for severe cases

How can Aminolevulinic Acid Dehydratase Deficiency Porphyria be Prevented?

• Currently, there are no specific methods or guidelines to prevent Aminolevulinic Acid Dehydratase Deficiency Porphyria, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risk before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Aminolevulinic Acid Dehydratase Deficiency Porphyria

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Aminolevulinic Acid Dehydratase Deficiency Porphyria? (Outcomes/Resolutions)

• The prognosis of Aminolevulinic Acid Dehydratase Deficiency Porphyria varies with the severity of the condition
• If neurological symptoms are severe involving the muscle and sensory faculties, then recovery may be prolonged

Additional and Relevant Useful Information for Aminolevulinic Acid Dehydratase Deficiency Porphyria:

The other acute porphyria forms include acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP).