ALA Dehydratase Deficiency Porphyria Clinical Presentation
- Author: Smeeta Sinha, MD; Chief Editor: Emmanuel C Besa, MD more...
ALAD deficiency porphyria (ADP) is an acute hepatic porphyria that produces only neurologic symptoms. Heterozygotes are asymptomatic.
The symptoms mimic those seen in acute intermittent porphyria, as follows:
- Abdominal pain is frequently reported; it is colicky in nature and may mimic a surgical abdomen
- Nausea, vomiting, constipation, diarrhea, and urinary retention are possible
- Neuropathy may be motor or sensory in nature; common symptoms include upper- and lower-extremity weakness and tingling
- Respiratory impairment is possible
- Seizures are possible
- Psychosis may occur in severe attacks
Exacerbation of symptoms occurs with stress, decreased calorie intake, and alcohol consumption. Note: This form of porphyria is not associated with cutaneous photosensitivity
The clinician should rule out the following:
- Exposure to exogenous inhibitors of ALAD, including styrene, lead, trichloroethylene, and bromobenzene
- Hereditary tyrosinemia, which leads to accumulation of succinylacetone, an ALAD inhibitor
On physical examination, patients with ALAD deficiency porphyria (ADP) may show evidence of abdominal tenderness or neuropathy. Autonomic neuropathy, including tachycardia and systemic arterial hypertension, are common presenting signs during acute attacks. Bulbar and respiratory muscle paresis can occur. Muscle hypotonia of the arms and legs is noted in some patients.
ALAD deficiency porphyria (ADP) is an autosomal recessive porphyria due to mutations in the ALAD gene on chromosome band 9q34. The heterogeneity of the mutations accounts for the varied phenotypes in the 7 studied cases. Erythrocyte ALAD activity is 1% of normal in homozygotes and 50% of normal in heterozygotes.
Precipitants of the acute attack include the following:
- Decreased caloric intake
- Drugs that induce the cytochrome P-450 system: Classically unsafe drugs include barbiturates (eg, phenobarbital), diphenylhydantoin, griseofulvin, phenytoin, sulfonamides, and valproic acid.
- Estrogen or progesterone use
- Acute physical and psychologic stressors
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