ALA Dehydratase Deficiency Porphyria Clinical Presentation

  • Author: Smeeta Sinha, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Nov 29, 2011
 

History

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.
    • 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.
  • Rule out exposure to exogenous inhibitors of ALAD, including styrene, lead, trichloroethylene, and bromobenzene.
  • Rule out hereditary tyrosinemia, which leads to accumulation of succinylacetone, an ALAD inhibitor.
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Physical

Physical examination in those affected by 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.
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Causes

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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Contributor Information and Disclosures
Author

Smeeta Sinha, MD  Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School

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

Disclosure: Nothing to disclose.

Coauthor(s)

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, and Sigma Xi

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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, and Society of University Urologists

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, 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 College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

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  6. Gross U, Sassa S, Jacob K, et al. 5-Aminolevulinic acid dehydratase deficiency porphyria: a twenty-year clinical and biochemical follow-up. Clin Chem. Sep 1998;44(9):1892-6. [Medline]. [Full Text].

  7. Akagi R, Kato N, Inoue R, et al. delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations. Mol Genet Metab. Apr 2006;87(4):329-36. [Medline].

  8. Seth AK, Badminton MN, Mirza D, Russell S, Elias E. Liver transplantation for porphyria: who, when, and how?. Liver Transpl. Sep 2007;13(9):1219-27. [Medline]. [Full Text].

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  12. de Verneuil H, Doss M, Brusco N, Beaumont C, Nordmann Y. Hereditary hepatic porphyria with delta aminolevulinate dehydrase deficiency: immunologic characterization of the non-catalytic enzyme. Hum Genet. 1985;69(2):174-7. [Medline].

  13. Inoue R, Akagi R. Co-synthesis of human delta-aminolevulinate dehydratase (ALAD) mutants with the wild-type enzyme in cell-free system-critical importance of conformation on enzyme activity. J Clin Biochem Nutr. Nov 2008;43(3):143-53. [Medline].

  14. Maruno M, Furuyama K, Akagi R, et al. Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria. Blood. May 15 2001;97(10):2972-8. [Medline]. [Full Text].

 
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