Test ID: ALAD
Aminolevulinic Acid Dehydratase (ALA-D), Whole Blood

Confirmation of a diagnosis of aminolevulinic acid dehydratase deficiency porphyria

Aminolevulinic acid dehydratase (ALA-D) activity can be inhibited in other situations including hereditary tyrosinemia type 1, lead intoxication, and exposure to styrene, trichloroethylene, or bromobenzene. These causes should be ruled out when considering a diagnosis of ALA-D deficiency porphyria (ADP). 

Note: This assay re-activates ALA-D that has been inhibited by lead. Therefore it is not useful in assessment of lead intoxication.

Porphyrias are a group of inherited disorders resulting from an enzyme deficiency in the heme biosynthetic pathway. Delta-aminolevulinic acid (ALA) dehydratase (ALA-D) catalyzes the second step in heme synthesis, the condensation reaction of 2 molecules of ALA into porphobilinogen (PBG). ALA-D deficiency porphyria (ADP) results from a deficiency of ALA-D, which causes ALA accumulation in the body with subsequent excretion of excessive amounts in the urine. PBG excretion remains normal, which rules out other forms of acute porphyria.

ADP is an acute hepatic porphyria that produces neurologic symptoms similar to those seen in acute intermittent porphyria. Symptoms include acute abdominal pain, peripheral neuropathy, nausea, vomiting, constipation, and diarrhea. Respiratory impairment, seizures, and psychosis are all possible during an acute period. ADP is extremely rare. Only 7 cases have been identified and confirmed since it was first described in 1979. ADP is characterized as an autosomal recessive inheritance pattern.

For additional information on the recommended order of testing, see Porphyria (Acute) Testing Algorithm and Porphyria (Cutaneous) Testing Algorithm in Special Instructions.

For additional information, see The Heme Biosynthetic Pathway in Special Instructions.

> or =4.0 nmol/L/sec

3.5-3.9 nmol/L/sec (indeterminate)

<3.5 nmol/L/sec (diminished)

In patients with deficiency porphyria (ADP), erythrocyte aminolevulinic acid (ALA) dehydratase (ALA-D) activity is typically reduced by 80%, or more, from normal levels.

ALA-D activity can be inhibited in other situations including hereditary tyrosinemia type 1, lead intoxication, and exposure to styrene, trichloroethylene, and bromobenzene. Therefore, these causes should be ruled out when considering a diagnosis of ADP.

Abstinence from alcohol for at least 24 hours prior to specimen collection is essential as ethanol suppresses aminolevulinic acid (ALA) dehydratase (ALA-D) activity.

This assay re-activates ALA-D that has been inhibited by lead. Therefore it is not useful in assessment of lead intoxication.

It is essential to proceed expeditiously with obtaining, processing, and dispatching the specimen, paying special heed to maintaining low temperatures (see "Specimen Required"). Failure to adhere to these directions may result in enzyme degradation, yielding false-positive values.

1. Tefferi A, Colgan JP, Solberg LA Jr: Acute porphyrias: diagnosis and management. Mayo Clin Proc 1994;69:991-995

2. Nuttall KL, Klee GG: Analytes of hemoglobin metabolism – porphyrins, iron, and bilirubin. In Tietz Textbook of Clinical Chemistry 5th edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 2001, pp 584-607

3. Ellefson RD: Porphyrinogens, porphyrins and the porphyrias. Mayo Clin Proc 1982;57:454-458

4. Ford RE, Ou CN, Ellefson RD: Assay for erythrocyte uroporphyrinogen I synthase activity, with porphobilinogen as substrate. Clin Chem 1980;26:1182-1185

5. Anderson KE, Sassa S, Bishop DF, et al: Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In The Metabolic Basis of Inherited Disease. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 2991-3062

• The Heme Biosynthetic Pathway
• Informed Consent for Genetic Testing
• Porphyria (Acute) Testing Algorithm
• Porphyria (Cutaneous) Testing Algorithm