[Date]
[Insurance Company]
[Address 1]
[Address 2]
[City State Zip]
Re: [Patient Name]
Insurance ID: [ID #]
DOB: XX/XX/XXXX
To whom it may concern,
I am writing on behalf of my patient to recommend DNA diagnostic testing for citrin deficiency due to mutations
in the SLC25A13 gene. Citrin deficiency is an inborn error of metabolism. Specifically, citrin deficiency is a urea
cycle disorder that results in decreased aspartate transport and, therefore, a decreased ability of the enzyme
argininosuccinate synthase to produce argininosuccinate and an increased NADH/NAD+ ratio, which impacts
several cellular processes, including glycolysis, gluconeogenesis, and fatty acid synthesis.
Citrin deficiency results in two distinct phenotypes: citrullinemia type II (CTLN2) and neonatal intrahepatic
cholestasis caused by citrin deficiency (NICCD). This patient is suspicious for [CTLN2 OR NICCD].
CTLN2 is often adult-onset, and patients present suddenly with recurrent episodes of hyperammonemia and
associated neuropsychiatric symptoms, including loss of memory, aberrant behaviors, disorientation, flapping
tremor, convulsive seizures, and potentially death from cerebral edema. Patients may have fatty infiltration and
mild fibrosis of the liver, pancreatitis, and hyperlipidemia. Treatment for this condition includes a lowcarbohydrate diet rich in lipids and protein, avoidance of alcohol, administration of arginine to prevent
hyperammonemic attacks, and liver transplant.
NICCD usually presents in infancy with transient intrahepatic cholestasis. Patients may have fatty liver, hepatic
fibrosis, jaundice, failure to thrive, low birth weight, and cataracts. Metabolic abnormalities can include elevated
levels of plasma citrulline, methionine, threonine, arginine, galactose, and tyrosine (without elevation of urinary
succinylacetone). Hemolytic anemia, hypoglycemia, elevated bilirubin, elevated bile acid concentrations,
decreased coagulation factors, and an elevated concentration of alpha-fetoprotein may also be present. Treatment
for this condition may include lactose-free formula (as for patients with galactosemia), medium-chain triglyceride
(MCT) oil, protein supplements, and, in severe cases, liver transplant.
Molecular testing for mutations in SLC25A13 is particularly helpful in patients when the phenotype is unclear,
when biochemical values are borderline, and to distinguish citrin deficiency from citrullinemia type I (due to
mutations in the ASS1 gene). This patient is suspicious for citrin deficiency based on [describe symptomatology]
and/or family history [describe]. If a germline mutation is identified in this patient, his/her recommended
treatment and medical management will be significantly altered.
Please note that this test is performed for clinical management in a laboratory that is CLIA approved for high
complexity testing.
From www.aruplab.com
Revision 1
Created: xx/xx/xxxx
Authorization should be obtained for:
Test name: [Test name]
Facility: ARUP Laboratories
CPT codes: [CPT codes]
Diagnosis code: [Diagnosis code]
Thank you for your time and attention to this matter.
Sincerely,
[Name of Ordering Physician]
From www.aruplab.com
Revision 1
Created: xx/xx/xxxx