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Metabolic Disease and Stroke - Propionic Acidemia: Treatment & Medication

Author: Pitchaiah Mandava, MD, PhD, Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Coauthor(s): Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Nov 4, 2008

Treatment

Medical Care

Medical care for patients with propionic acidemia includes the following:

  • A low-protein diet (1.5-2 mg/kg/d), L-carnitine supplementation (100 mg/kg/d), and biotin supplementation (10 mg/d) are required.
  • Carnitine, an enzyme involved in the metabolism of long-chain fatty acids, buffers the acyl-CoA metabolites that accumulate with protein-restricted diets. The acyl-carnitine that is produced by the buffering action is excreted in the urine.
  • Biotin is a cofactor for propionyl-CoA carboxylase (and for 3 other carboxylases). Therefore, propionic acidemia may be present in a patient, as the broader metabolic problem of multiple carboxylase deficiency.
    • Biotin responsiveness may depend on the genetic heterogeneity of isolated propionic acidemia and propionic acidemia existing as a subset of multiple carboxylase deficiency.
    • In patients with biotin-unresponsive disease, restricting their intake of isoleucine, valine, threonine, and methionine is the only solution.
  • Prompt dietary modification and supplementation may reverse clinical symptoms and normalize laboratory findings.
    • The success of therapy can be measured as changes in propionic acid level in the serum.
    • In-home testing of urine for ketones, especially during suspected infections, has been advocated.
  • In the acute phase, identify and treat intercurrent infections that have triggered an acidotic episode.
    • Dietary modifications must be made in a hospital setting.
    • Dialysis may be required for life-threatening acute phases of illnesses that are triggered by infections or other stresses.
    • Because gastrointestinal bacteria produce propionic acid, neomycin and metronidazole have been proposed as treatments. Clinical data about this treatment regimen are limited.
  • Organ transplantation of the liver or of the liver and kidney has been attempted. However, perioperative and postoperative complications are apparently high, and the long-term benefits are unclear.2

Consultations

  • Consultation with a pediatric neurologist is necessary when a patient presents with stroke, seizure, or encephalopathy.
  • Dietary and/or nutritional specialists may help in modifying the patient's diet.
  • A physical therapist and/or an occupational therapist should also be consulted for functional assessment and therapeutic recommendations.
  • After the diagnosis of propionic acidemia is confirmed, a geneticist should be consulted.

Diet

A protein-restricted diet (0.5-1.5 g/kg/d) with L-carnitine and biotin supplementation is required.

Medication

The goals of pharmacotherapy for propionic acidemia are to reduce morbidity and prevent complications.

Essential coenzyme

This is a critical cofactor for essential metabolic processes.


Biotin

Coenzyme for propionyl-CoA carboxylase as well as 3 other carboxylases.

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

None reported

Nutritional supplement

This is used to correct metabolic deficiencies.


Levo-carnitine (L-carnitine)

Can promote excretion of excess fatty acids in patients with defects in fatty acid metabolism or specific organic acidopathies in which acyl-CoA esters accumulate; reduced ketogenesis in response to fasting; may help with relative carnitine deficiency in propionic acidemia.

Adult

Pediatric

100 mg/kg/d PO (IV formulation also available)

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Body odor, nausea, and gastritis; D-isomer may not be therapeutically useful in this condition; monitor blood chemistries, plasma carnitine concentrations, vital signs, and patients' overall clinical condition

More on Metabolic Disease and Stroke - Propionic Acidemia

Overview: Metabolic Disease and Stroke - Propionic Acidemia
Differential Diagnoses & Workup: Metabolic Disease and Stroke - Propionic Acidemia
Treatment & Medication: Metabolic Disease and Stroke - Propionic Acidemia
Follow-up: Metabolic Disease and Stroke - Propionic Acidemia
References
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References

  1. Surtees RA, Matthews EE, Leonard JV. Neurologic outcome of propionic acidemia. Pediatr Neurol. Sep-Oct 1992;8(5):333-7. [Medline].

  2. Leonard JV, Walter JH, McKiernan PJ. The management of organic acidaemias: the role of transplantation. J Inherit Metab Dis. Apr 2001;24(2):309-11. [Medline].

  3. Al-Essa M, Bakheet S, Patay Z, et al. 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in propionic acidemia: clinical and MRI correlations. Brain Dev. Jul 1999;21(5):312-7. [Medline].

  4. Bergman AJ, Van der Knaap MS, Smeitink JA, et al. Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia: clinical and biochemical considerations. Pediatr Res. Sep 1996;40(3):404-9. [Medline].

  5. Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol. Sep 1994;15(8):1459-73. [Medline].

  6. Brismar J, Ozand PT. CT and MR of the brain in the diagnosis of organic acidemias. Experiences from 107 patients. Brain Dev. Nov 1994;16 Suppl:104-24. [Medline].

  7. Clavero S, Perez B, Rincon A, et al. Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes. Hum Genet. Aug 2004;115(3):239-47. [Medline].

  8. Fenichel GM. Clinical Pediatric Neurology: A Signs and Systems Approach. 1996:11-2.

  9. Fenton WA, Rosenberg LE. Disorders of propionate and methyl-malonate metabolism. In: The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 1995:1423-9.

  10. Haas RH, Marsden DL, Capistrano-Estrada S, et al. Acute basal ganglia infarction in propionic acidemia. J Child Neurol. Jan 1995;10(1):18-22. [Medline].

  11. Hamilton RL, Haas RH, Nyhan WL, et al. Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions. J Child Neurol. Jan 1995;10(1):25-30. [Medline].

  12. Hoffmann GF, Gibson KM, Trefz FK, et al. Neurological manifestations of organic acid disorders. Eur J Pediatr. 1994;153(7 suppl 1):S94-100. [Medline].

  13. Mass General Hosp. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1998. A 13-year-old girl with a relapsing-remitting neurologic disorder [clinical conference]. N Engl J Med. Dec 24 1998;339(26):1914-23. [Medline].

  14. Miyazaki T, Ohura T, Kobayashi M, et al. Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescue by postnatal, liver-specific supplementation via a transgene. J Biol Chem. Sep 21 2001;276(38):35995-9. [Medline].

  15. Nyhan WL, Bay C, Beyer EW, Mazi M. Neurologic nonmetabolic presentation of propionic acidemia. Arch Neurol. Sep 1999;56(9):1143-7. [Medline].

  16. Nyhan WL, Skati NA. Propionic acidemia. In: Diagnostic Recognition of Genetic Disease. 1987:36-41.

  17. Perez-Cerda C, Merinero B, Marti M, et al. An unusual late-onset case of propionic acidaemia: biochemical investigations, neuroradiological findings and mutation analysis. Eur J Pediatr. Jan 1998;157(1):50-2. [Medline].

  18. Rincon A, Aguado L, Desviat LR et al. Propionic and Methylmalonic Acidemia: Antisense Therapeutics for Intronic Variations Causing Aberrantly Spliced Messenger RNA. Am J Hum Genet. 2007;81:1262-1270. [Medline].

  19. Sethi KD, Ray R, Roesel RA, et al. Adult-onset chorea and dementia with propionic acidemia. Neurology. Oct 1989;39(10):1343-5. [Medline].

  20. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. 1999;245-54. [Full Text].

  21. Swaiman KF. Aminoacidopathies and organic acidemias resulting from deficiency of enzyme activity. In: Pediatric Neurology. Principles and Practice. 1994:1215-9.

  22. Wolf B, Hsia YE, Sweetman L, et al. Propionic acidemia: a clinical update. J Pediatr. Dec 1981;ID - AM 25675/AM/NIADDK(6):835-46. [Medline].

  23. Yorifuji T, Kawai M, Muroi J, et al. Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications. Hum Genet. Aug 2002;111(2):161-5. [Medline].

  24. Zweifler RM. Management of acute stroke. South Med J. Apr 2003;96:380-5. [Medline].

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Further Reading

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Keywords

propionic acidemia, propionyl-coenzyme A, CoA, carboxylase, bilateral basal ganglia infarcts, caudate infarct, putaminal infarct, globus pallidus infarct, PCCA, PCCB, metabolic disease and stroke, metabolic disorder, accumulation of propionic acid, biotin

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Contributor Information and Disclosures

Author

Pitchaiah Mandava, MD, PhD, Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Pitchaiah Mandava, MD, PhD is a member of the following medical societies: American Academy of Neurology, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences, Royal Society of Medicine, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Richard M Zweifler, MD, Chief of Neurology, Sentara Healthcare, Norfolk, VA
Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Stroke Association, Royal Society of Medicine, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center
Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Concentric Medical Consulting fee Review panel membership; Abbott Consulting fee Consulting; Sanofi  Consulting

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