Metabolic Consequences of CPT-1 Deficiency

Study Overview
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Brief Summary
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The purpose of this study is to learn more about how long children with CPT-1 deficiency can wait between meals without developing low blood sugar or symptoms of low blood sugar. The other purpose is to learn more about how much fat is stored in the liver of a child with CPT-1 deficiency.

Detailed Description
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With the advent of enhanced screening (via tandem mass spectroscopy, MS/MS), the Northwest Regional Newborn Screening Program (NWRNSP) has identified a high incidence of carnitine palmitoyl transferase type 1A (CPT1A) deficiency in Alaska Native infants. Since October of 2003 approximately 80 Alaska Native infants have been identified with this condition; previously only 30 published cases were known worldwide. All of the infants are homozygous for a c.1436C-T sequence variant in the CPT1A gene, which results in the substitution of a leucine for proline at amino acid position 479 (P479L), and an approximately 80% reduction of CPT1A activity (non-classic CPT1A deficiency) (7). The clinical implications of this very restricted level of enzyme activity are not known. However, patients with more severe reductions of CPT1A activity (as the result of other mutations) are known to be at high risk for hypoketotic hypoglycemia, liver dysfunction, and sudden unexplained death (1). Hepatomegaly with micro- and macro-vesicular steatosis is also common (16). Currently the treatment of Alaska Native infants and children with CPT1A deficiency is based on data from patients with more severe forms of CPT1A deficiency and other fatty acid oxidation (FAO) disorders. Our ultimate goal is to establish evidence-based guidelines for treatment of the form of CPT1A deficiency prevalent in the Alaska Native population. This pilot study addresses two specific questions and will provide the first glimpse of the physiologic effects of homozygosity for the c.1436C-T sequence variant in the CPT1A gene. These data will aid in the development of strategies for clinical management that can be evaluated in future prospective studies, and provide preliminary data required for applications for NIH funding for more in-depth characterization of the clinical consequences of this condition.

Official Title
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Metabolic Consequences of CPT1A Deficiency in Alaska Native Children

Conditions
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Carnitine Palmitoyl Transferase Type 1A (CPT1A) Deficiency

Intervention / Treatment
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* Other: Medically supervised fasting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CPT-1 deficiency homozygous for the c.1436C-T sequence variant greater than 6 kg otherwise healthy siblings must be free of CPT-1 deficiency but heterozygous for c.1436C-T sequence variant and otherwise healthy Exclusion Criteria: liver dysfunction diabetes renal disease metal plate in body

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Medically supervised fasting|Metabolic fasting studies will be conducted over an 18-hour period or until blood glucose is < 40 mg/dl. If the YSI reading is 40 mg/dl or less, at any time during the study, then a blood sample will be collected, and the fast terminated by giving D25W IV and then feeding orally.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare body composition, liver and muscle lipid content, and liver function of Alaska Native children with CPT1A deficiency, with similar measures in their unaffected siblings. |  | February 2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the metabolic response of Alaska Native children with CPT1A deficiency to fasting, |  | February 2009 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPT1A, steatosis, deficiency, metabolic, response, fasting