The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
Objectives:

 -  To study nutrition and immune system problems in people with urea cycle disorders.

 -  To study how people with urea cycle disorders and healthy volunteers respond to standard
 flu and/or hepatitis A vaccines.

 -  To compare differences in nutrition and immune systems of people with urea cycle
 disorders with that of healthy volunteers.

 Eligibility:

 -  Healthy males and females at least 2 years of age who are able to travel to the National
 Institutes of Health hospital in Bethesda, MD

 -  Males and females at least 2 years of age who have a urea cycle disorder and are able to
 travel to the National Institutes of Health hospital in Bethesda, MD.

 Design:

 For Patients with urea cycle disorder:

 -  Participants will spend 2 to 3 days in the National Institutes of Health hospital for
 the following tests:

 -  A physical exam and review of medical history

 -  Food log for 3 days before the start of the study

 -  Blood tests

 -  24-hour urine collection

 -  Resting metabolism test

 -  DEXA scan imaging study of bones and body fat

 -  Participants who are old enough to do certain tasks by themselves (like dressing and
 eating) can choose to have the following extra tests:

 -  24-hour metabolic room measurements

 -  BodPod(Registered Trademark) study to measure bones and body fat

 -  Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the
 study and will be monitored to check for possible side effects.

 -  Participants will return within 1 to 3 months for follow-up tests/immunizations.

 For Healthy Volunteers:

 -  Participants will be seen at the outpatient clinics at the National Institutes of Health
 hospital for up to 2 visits for the following:

 -  Review food log completed 3 days before the start of the study

 -  Blood tests

 -  Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the
 study and will be monitored to check for possible side effects.

 -  Participants will return within 1 to 3 months for follow-up tests/immunizations.

 -  Review of second food log completed 3 days before second outpatient visit
Urea cycle disorders (UCD) are amongst the most frequent of the inborn errors of metabolism
 (IEM) and result from a block in the hepatic disposal of waste nitrogen from protein
 catabolism. Viral infections play a significant role in precipitating life-threatening acute
 hyperammonemic crises in UCD. The recent H1N1 influenza pandemic has placed this vulnerable
 population at significant risk. The standard of care for these patients is routine
 vaccination for seasonal and H1N1 influenza viruses. However, nutritional deficiencies and
 their underlying enzymopathy may affect the efficacy of vaccination.

 Dietary management of urea cycle disorders includes dietary modification with protein
 restriction. Protein energy malnutrition, essential fatty acid deficiencies and micronutrient
 deficiencies due to restrictive dietary management have been reported in various inborn
 errors of metabolism. In general, dietary deficiencies and their effect on immune function
 are well documented.

 In addition to the disposal of waste nitrogen, the urea cycle also generates arginine for
 various biologic functions. Depending on the site of the metabolic block, UCD patients are at
 risk for becoming systemically deficient in citrulline and arginine, with potential
 implications for the immune system. The immunomodulatory roles of the amino acids citrulline
 and arginine have been characterized in the context of nutritional deficiencies in disease
 states such as cancer and sepsis. Systemic infection may also deplete systemic citrulline and
 arginine, compounding an underlying deficiency in UCD. Cells of the immune system have a more
 direct relationship with the urea cycle: urea cycle enzymes arginosuccinate synthetase (ASS),
 arginosuccinate lyase (ASL) and arginase (ARG1) may also be components of leukocyte
 metabolism. Overall, general and specific nutritional deficiencies and enzymopathies
 affecting leukocyte metabolism may potentially affect vaccine efficacy. However, immune
 system function in experiments of nature such as UCD remains an understudied area.

 In this protocol, we will clinically evaluate the nutritional/metabolic and immunologic
 states of patients with UCD or related disorders. Routine inpatient admissions will last 2-3
 days and involve urine collection, blood drawing, radiological procedures, nutrition
 assessment and biometrics, and vaccination for combined seasonal/H1N1 influenza. Follow-up
 outpatient appointments will be scheduled at the end of the study period.

 The study objectives will be to describe the nutritional and immune deficiencies seen, query
 for nutrition/enzymatic/immunologic correlations in this patient population, describe vaccine
 efficacy in this patient population, and search for new genes in rare families that have
 evidence for an unknown class of UCD. The population will consist of patients previously
 evaluated at NIH, physician referrals, and families directed to the study from
 clinicaltrials.gov as well as the National Urea Cycle Disorders Foundation. All patients will
 be evaluated at the NIH Clinical Center.
-  INCLUSION CRITERIA:

 Patients:

 Any gender and ethnicity age 2 years and older with a diagnosis of a urea cycle disorder
 are eligible to enroll in this protocol.

 Patients need to be medically and nutritionally managed by a local metabolic provider. If
 necessary, we will obtain written consent from the patient to review medical records from
 their home physician to confirm eligibility.

 Healthy Volunteers:

 Any gender and ethnicity age 2 years and older are eligible to enroll in this protocol.

 Have access to own personal medical provider <TAB>

 EXCLUSION CRITERIA:

 Less than 2 years of age

 Inability to travel to NIH because of their medical condition

 Recent (6 month) history of vaccination or immune modulating drug

 Severe reactions to eggs and or latex

 History of severe reactions to previous immunizations (e.g. hives, rash, difficulty
 breathing)

 Persons without a personal medical provider

 Persons with current infections or under care of medical provider for an ongoing medical
 issue