eMedicine Specialties > Dermatology > Pediatric Diseases

Homocystinuria: Treatment & Medication

Author: Janette Baloghova, MD, PhD, Lecturer, Department of Dermatology, Medical Faculty, University of PJ Safarik at Kosice, Slovak Republic
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Zuzana Baranova, MD, PhD, Senior Lecturer, Department of Dermatology, University of PJ Safarik at Kosice, Slovak Republic
Contributor Information and Disclosures

Updated: May 14, 2009

Treatment

Medical Care

  • The diagnosis should be established as early as possible. Neonates in whom homocystinuria is diagnosed have had a benign course when they are fed on methionine-restricted cysteine-supplemented diets. Cysteine can be supplemented to a maximum of 500 mg/d.
  • The administration of pyridoxine in high doses (300-600 mg/d) is effective in some patients.
  • Other possible treatments include the use of folic acid (in pharmacologic doses), betaine (3-methylglycine decreases serum concentrations of homocysteine), or cyanocobalamin, as well as symptomatic supportive measures.
  • Homocysteine Reduction Formula, a special nutritional supplement created by Brimhall, can also lower homocysteine levels.
  • In patients with hypothyroidism, treatment with L-thyroxine can normalize homocysteine levels.
  • Betaine improves metabolic control in B6-nonresponsive patients with homocystinuria after optimum dietary control.32,33,34
    • Betaine therapy can precipitate cerebral edema, although the exact mechanism is uncertain. Betaine does raise the methionine level, and cerebral edema can occur when plasma methionine values exceed 1000 µmol/L. Methionine levels must be monitored in patients with cystathionine beta-synthase deficiency who are on betaine; consider betaine as an adjunct, not an alternative, to dietary control.35,36
    • However, even when patients' serum betaine concentrations are increased by supplementation, serum homocysteine concentrations are often not lowered to the reference range. Following a low-methionine diet that keeps serum methionine within the reference range may be necessary when treating patients with homocystinuria due to cystathionine beta-synthase deficiency when betaine is administered.
    • Conventional treatment of cystathionine beta-synthase deficiency by diet and pyridoxine/betaine normalizes many, but not all, metabolic abnormalities associated with cystathionine beta-synthase deficiency. The finding of low plasma serine concentrations in patients with untreated cystathionine beta-synthase deficiency may merit further exploration because supplementation with serine might be a novel and safe component of treatment of homocystinuria.

Surgical Care

  • Surgical treatment should be considered, especially in patients with pupillary-block glaucoma or in those with recurrent lens dislocation into the anterior chamber.
  • Other ophthalmologic or orthopedic disorders should be corrected.

Consultations

  • An ophthalmologist should be consulted for the treatment of repeated lens dislocation, acute pupillary-block glaucoma, and other ophthalmologic disorders.
  • An orthopedist should be consulted to correct orthopedic disorders.

Diet

  • Patients must maintain a diet with limited amounts of protein (1 g/kg) and amino acid mixtures. The diet must be free of protein hydrolysate.
  • Patients in whom the disease does not respond to pyridoxine supplements must be treated with dietary reductions in methionine and with cysteine supplementation.

Medication

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

Dietary supplements

These agents are used to correct nutritional deficiencies.


Cysteine

Sulfur-containing amino acid. Generally considered an essential amino acid in infants.

Adult

500 mg/d IV

Pediatric

Not established

Tetracyclines may reduce protein-sparing effects of infused amino acids because of their antianabolic activity

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

Do not withdraw venous blood for blood chemical test through peripheral infusion site (may interfere with assessment of nitrogen-containing substances); hyperammonemia most common in children with renal or hepatic disease (reaction is dose dependent and likely to develop during prolonged therapy)


Betaine anhydrous (Cystadane)

Antihomocystinuric that acts as a methyl-group donor in the remethylation of homocysteine to methionine, removing excess homocysteine from the body.

Adult

6 g/d PO divided bid; not to exceed 20 g/d

Pediatric

<3 years: 100 mg/kg/d PO initially; increase weekly in 100-mg/kg increments; not to exceed 20 g/d
>3 years: Administer as in adults

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

Diarrhea and nausea; CNS changes

Vitamins

Vitamins are essential for normal DNA synthesis.


Pyridoxine (Nestrex)

Involved in synthesis of GABA in CNS.

Adult

300-600 mg PO qd

Pediatric

Not established

May decrease serum levels of levodopa, phenytoin, and phenobarbital

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

>200 mg/d may precipitate withdrawal effects when discontinued


Cyanocobalamin (Cyomin, Crysti 1000, Crystamine)

Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or plants.

Adult

25-250 PO mcg/d

Pediatric

Administer as in adults

Documented hypersensitivity; hereditary optic nerve atrophy

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Severe hypokalemia may result in vitamin B-12 megaloblastic anemia (may be fatal) because of increased cellular potassium requirements when anemia is corrected


Folic acid (Folvite)

Important cofactor for enzymes used in red blood cell production.

Adult

5 mg PO/IM/SC qd

Pediatric

<12 years: Not established
>12 years: 1 mg PO/IM/SC qd

Increased seizure frequency and subtherapeutic phenytoin levels reported with concurrent use

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Benzyl alcohol (preservative in some preparations) associated with fatal gasping syndrome in premature infants; resistance to treatment possible with alcoholism and other vitamin deficiencies

More on Homocystinuria

Overview: Homocystinuria
Differential Diagnoses & Workup: Homocystinuria
Treatment & Medication: Homocystinuria
Follow-up: Homocystinuria
References
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References

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Further Reading

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Keywords

homocystinuria, homocysteine, cystathionine synthase deficiency, cystathionine beta-synthase deficiency, CBS deficiency, metabolic disorder, methionine metabolism

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Contributor Information and Disclosures

Author

Janette Baloghova, MD, PhD, Lecturer, Department of Dermatology, Medical Faculty, University of PJ Safarik at Kosice, Slovak Republic
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-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.

Zuzana Baranova, MD, PhD, Senior Lecturer, Department of Dermatology, University of PJ Safarik at Kosice, Slovak Republic
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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