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ALA Dehydratase Deficiency Porphyria Clinical Presentation

  • Author: Smeeta Sinha, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Mar 26, 2015


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.[9] 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
Contributor Information and Disclosures

Smeeta Sinha, MD Resident Physician, Department of Dermatology, Rutgers New Jersey Medical School

Smeeta Sinha, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa, Sigma Xi

Disclosure: Nothing to disclose.


Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Pere Gascon, MD, PhD Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain

Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Thomas H Davis, MD, FACP Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Geisel School of Medicine at Dartmouth

Thomas H Davis, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Education, American College of Physicians, New Hampshire Medical Society, Phi Beta Kappa, Society of University Urologists

Disclosure: Nothing to disclose.


Mark J Shumate, MD, MPH Assistant Professor, Department of Internal Medicine, Division of Hematology/Oncology, Emory University School of Medicine

Mark J Shumate, MD, MPH is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

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