Medical Information on Urea Cycle Disorders

Arginine HCl vs. and arginine base:

  • Arginine HCl is given intravenously (IV) to UCD patients in the hospital setting. Arginine HCl is sometimes used by pharmacists to create a pediatric suspension (liquid) for oral use in UCD children. Arginine HCl can cause acidosis. Patients receiving arginine HCl may require additional monitoring for acidosis by their metabolic physician.
  • Arginine free base powder is the standard used for daily oral administration for chronic management of some urea cycle disorders. It does not cause acidosis.

Families should check to ensure the product they are receiving from their pharmacy for oral administration is arginine free base. If arginine HCl has been substituted by the pharmacy, the metabolic physician needs to be notified in case additional monitoring for acidosis is needed. Even healthcare professionals are not always aware of the difference in these two products.

With an increasing amount of unregulated dietary supplement products on the market, it is very important to stay vigilant and make sure which form of arginine you are receiving from the pharmacy. Some pharmacies have started distributing Arginine HCl powder instead of Arginine free base powder to patients without notifying the patient/family or treating physician of the substitution. Your metabolic physician will determine whether it is safe to continue on arginine HCl and whether additional monitoring is needed. If the physician wishes the patient to receive arginine free base only, the prescription must state explicitly "arginine free base." 

Feb 14, 2014 FDA DRUG RECALL - CITRULLINE: L-citrulline manufactured by Medisca, a supplier to hospitals and pharmacies, was recalled. Lots 95482/A, 95482/B, 95482/C, 95482/D &96453/A, 96453/B, 96453/C, 96453/D contained ZERO citrulline. The product contained a different amino acid, L-acetyl-leucine. This resulted in reports of severe side effects including metabolic instability, hyperammonemia, hair loss, stomach pains and other symptoms. The FDA issued a warning and  manufacturer recall HERE. Adverse events should be reported on FDA MedWatch HERE. Please notify your pharmacy and your metabolic physician immediately if you notice a change or difference in the usual color, consistency, or odor of UCD treatment amino acid supplements. The amino acid supplements can be tested for purity to ensure that the product contains the labeled quality/strength. If you suspect an issue with your citrulline or arginine, contact NUCDF for more information on how to get the product tested.

FDA Drug Warning - Valproic Acid (trade name Depakote, anticonvulsant) strongly contraindicated in UCD patients.

Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of valproate therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy or postpartum encephalopathy unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs and symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying urea cycle disorders. For more information, click here.

Warning - Corticosteroid (prednisone, Solu-Medrol, etc.) & Haloperidol Contraindication: Use of these medications may cause breakdown of body protein and result in fatal increase in plasma ammonia levels.

Risk of Urea Cycle Disorder following Gastric Bypass (Bariatric) Surgery: More information

Sodium Phenylbutyrate for treatment of Urea Cycle Disorders Medication usage precaution:  When administered as part of a drug treatment regimen for urea cycle disorders, sodium phenylbutyrate should not be exposed to heat, or mixed or taken with any acidic beverages such as orange juice, lemonade, etc. 

DISORDER DESCRIPTIONS

Ornithine Transcarbamylase Deficiency (OTC)

OTC Deficiency (NCBI Database)

Carbamyl Phosphate Synthetase Def. (CPS)

CPS Deficiency (NCBI Database)

Argininosuccinic Acid Synthetase Def. (Citrullinemia)

Citrullinemia (NCBI Database)

Argininosuccinate Lyase Deficiency/Argininosuccinic Aciduria (ASA)

AL/ASA (NCBI Database)

Arginase Deficiency 

Arginase deficiency (NCBI Database)

N-acetylglutamate Synthetase Deficiency (NAGS)

NAGS (NCBI Database)

Hyperammonemia

Hyperammonemia-Hyperornithinemia-Homocitrullinemia Syndrome (HHH)
Carbonic Anhydrase VA Deficiency (CA-VA)
Citrullinemia Type II (Citrin Deficiency)
Lysinuric Protein Intolerance

Urea Cycle Disorders - GeneClinics Review

Urea Cycle Disorders Glossary (pdf)

TREATMENT / MANAGEMENT INFORMATION
Please contact NUCDF for individualized information
and support

Preventing Catabolism by Debra Geary Hook, MPH, RD

UCD Diagnosis and Treatment

Emergency Treatment of Neonatal Onset Urea Cycle Disorder

Liver Transplant for UCD in pediatric patients - pdf document
Pediatric Organ Transplantation for UCD and Organic Acidemias - pdf document

LABORATORY/GENETIC TESTING

Ravicti or Buphenyl (sodium phenylbutyrate) assay/blood level - an assay to measure levels of phenylacetate/phenylacetylglutamine in patients undergoing Ravicti or Buphenyl drug therapy. This blood test measures these analytes of the drugs, which is useful in determining whether the drugs are being properly metabolized by the body. This information can ultimately assist the patient’s metabolic physician in determining optimal dosing of Ravicti or Buphenyl and avoid the  possibility of underdosing/overdosing, either of which could result in metabolic instability and hyperammonemia.
 

 

"I will never forget how much NUCDF helped in diagnosing and management of Baby F., a South Asian baby whom we lost since we could not support him due to lack of resources.
As a paediatrician who treated Baby F. while getting advice from Dr. Batshaw online, I am very much impressed how dedicated are this professional and the members of NUCDF particularly Cindy who offered all possible help and advice in our effort to keep the life of that baby going. Although Baby F. was suffering in a remote corner of this globe, in South Asia, NUCDF was kind enough to reach out to help that little life until he died.
Keep up your excellent job.
Long live NUCDF"

Dr. R - U.K.