Clinical trial NCT00653666: Metabolic Consequences of CPT-1 Deficiency
Official title: Metabolic Consequences of CPT1A Deficiency in Alaska Native Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Carnitine Palmitoyl Transferase Type 1A (CPT1A) Deficiency
Keywords: CPT1A
steatosis
deficiency
metabolic
response
fasting
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Alaska Department of Health and Social Services
First posted: 2008-04-07
Enrollment: 12
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: February 2009
Secondary outcomes:
measure: To characterize the metabolic response of Alaska Native children with CPT1A deficiency to fasting,
timeFrame: February 2009
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Melanie B. Gillingham, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gillingham MB, Hirschfeld M, Lowe S, Matern D, Shoemaker J, Lambert WE, Koeller DM. Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant. Mol Genet Metab. 2011 Nov;104(3):261-4. doi: 10.1016/j.ymgme.2011.06.017. Epub 2011 Jun 28.