Clinical Guidance

The clinical manifestations of primary carnitine deficiency (PCD) can vary widely with respect to age of onset, organ involvement, and severity. The broad clinical spectrum ranges from metabolic decompensation in infancy to cardiomyopathy in childhood, fatigability in adulthood, and absence of clinical manifestations. PCD has typically been associated with an infantile metabolic presentation that usually presents before age two years in about half of untreated affected individuals. The remaining half have a childhood myopathic presentation that typically presents between ages two and four years with dilated cardiomyopathy, hypotonia, muscle weakness, and elevated creatine kinase (CK). However, adults with PCD and mild or no manifestations are likely underdiagnosed, making it difficult to determine the relative proportion of these presentations . Table 3. Primary Carnitine Deficiency: Select Features

Diagnostic Criteria

Suggestive Findings A diagnosis of primary carnitine deficiency (PCD) may be suspected due to an abnormal newborn screening result prior to onset of suggestive findings or may be considered because of symptoms of PCD . Scenario 1: Abnormal Newborn Screening (NBS) Result NBS for PCD is primarily based on use of dried blood spots collected between 24 hours and 72 hours after birth to quantify free carnitine (C0) concentration by tandem mass spectrometry. (For information on NBS by state in the United States, see www.newbornscreening.hrsa.gov.) Low concentration of free carnitine can identify (1) an infant with PCD, (2) a mother with PCD, or (3) both. NBS can identify a mother with PCD because transfer of carnitine across the placenta from an affected mother to her fetus results in a low plasma carnitine concentration in her newborn. Thus, an infant who does not have PCD but is born to a mother who has PCD can have low plasma carnitine concentrations shortly after birth, resulting in a false positive NBS result . Note: (1) NBS for PCD has low positive predictive value (e.g., 4.7% in California ). There are many factors that may affect NBS for PCD, including maternal carnitine deficiency, prematurity, pivalic acid-containing antibiotics, and some other inborn errors of metabolism. At least one country (New Zealand) has discontinued NBS for this disorder because of its very low sensitivity and positive predictive value . (2) In the US, most NBS laboratories determine their own cutoff levels for test results that are considered to be out of range and require further laboratory testing because out-of-range NBS results individually are not entirely specific to PCD. Positive NBS results (i.e., low blood concentrations of free carnitine) require evaluation of the newborn and mother as soon as possible and no later than three days after birth. • See and on how to make an analyte diagnosis or confirm a diagnosis molecularly. • For recommendations on presumptive treatment of affected newborns while awaiting diagnosis confirmation to prevent irreversible neurocognitive impairment, consult a metabolic specialist to discuss immediate treatment for PCD with oral levocarnitine supplementation and other recommended care. • If a metabolic specialist is not available, begin treatment for PCD with oral levocarnitine supplementation (typically 100-200 mg/kg/day, divided in three doses; see ) to prevent metabolic decompensation. Table 1. Primary Carnitine Deficiency: Testing Recommended at the Time of Diagnosis of Low Carnitine Blood Levels via NBS

Management Guidelines

No clinical practice guidelines for primary carnitine deficiency (PCD) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PCD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Surveillance Guidelines

In addition to regular evaluations by a metabolic specialist and metabolic dietician, the evaluations summarized in are recommended to monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations. Table 10. Primary Carnitine Deficiency: Recommended Surveillance