written by: R. Elizabeth C. Kitchen•edited by: lrohner•updated: 12/31/2010
Are you seeking information about the genetics of ALA dehydratase deficiency porphyria? Read on for this and more.
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ALA dehydratase deficiency porphyria, also referred to as ALAD porphyria, is very rare. Through understanding the genetics of ALA dehydratase deficiency porphyria it is known that this genetic disorder occurs when the patient has low levels of the enzyme necessary for for the second step in the production of heme. Heme is a molecule that is vital for all of the organs in the body. It is part of hemoglobin, a substance responsible for carrying oxygen in the blood. This condition is a porphyria subtype. This genetic disorder is very rare, and worldwide, less than ten cases have been reported.
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Through what is known about the genetics of ALA dehydratase deficiency porphyria, it is known that a minimum of ten ALAD gene mutations can cause this disorder. The changes caused by the mutation reduce the enzyme's activity, allowing toxic levels of delta-aminolevulinic acid to build up. This disorder is inherited in an autosomal recessive pattern.
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Signs and Symptoms
The signs and symptoms of this disorder have varied in the small amount of patients diagnosed with this disorder. Patients have experienced weak muscle tone during infancy, muscle pain or numbness, and acute attacks of muscle weakness and abdominal pain. Other possible signs and symptoms include nausea and vomiting, neuropathy, constipation, respiratory impairment, diarrhea, seizures, urinary retention, and in severe attack,s psychosis is possible. These signs and symptoms may originate during adulthood, infancy, or childhood.
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The most specific diagnostic test for this genetic disorder is DNA analysis to look for ALAD gene mutations. Laboratory tests may reveal the following:
Increased urine ALA levels
Elevated erythrocyte zinc protoporphyrin levels
Level of erythrocyte ALAD activity will usually be reduced by more than 80 percent of what is normal
Elevated protoporphyrin IX and coprotoporphyrin III levels
Levels of urine PBG are within reference range
Levels of fecal porphyrin are normal
The patient's blood-lead levels may be analyzed. When a patient is having an acute ADP attack, hyponatremia may be noted.
The patients signs and symptoms and medical history will also be evaluated.
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An acute attack may be treated with parenteral morphine, airway protection and mechanical ventilation if necessary, beta-blockers for hypertension and tachycardia, benzodiazepines or antiepileptic medications for seizure control, intravenous hematin for an acute attack, and phenothiazines for anxiety, nausea, and vomiting. A medication known as metalloporphyrin agents may help to prevent complications and reduce morbidity. Hemin therapy, when administered during an attack, may be beneficial in preventing an attack from resulting in neuronal degeneration. However, it will not repair neuronal damage. This medication is administered intravenously.
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Genetics Home Reference. (2009). Porphyria. Retrieved on December 30, 2010 from Genetics Home Reference: http://ghr.nlm.nih.gov/condition/porphyria
Sinha, S. MD et al. (2008). ALA Dehydratase Deficiency Porphyria. Retrieved on December 30, 2010 from eMedicine: http://emedicine.medscape.com/article/198248-overview