OBJECTIVES: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare genetic disorders stemming from inborn errors of metabolism. LC-FAOD are chronic diseases that present across a broad clinical spectrum, punctuated by episodes of acute, life-threatening, spontaneous decompensation, regardless of current status or subtype. Prior to newborn screening (NBS) implementation, LC-FAOD were diagnosed symptomatically, with asymptomatic or pre-symptomatic individuals going unidentified. While NBS has increased diagnosis rates, determining overall prevalence in the United States (US) is difficult because states implemented NBS at dissimilar rates, or number of subtypes screened was limited. This study describes an epidemiological model developed to estimate overall prevalence of LC-FAOD.

METHODS: A targeted literature review identified studies reporting LC-FAOD incidence, NBS, prevalence, disease severity, and mortality. Incidence rate was calculated as confirmed positive LC-FAOD cases divided by total number of live births. Incidence-derived prevalence was determined as combination of calculated incidence, survival estimates, and diagnosis rates. To apply the diagnostic rate to all country/state data, the diagnostic criteria, rates of misdiagnosis, delayed diagnosis, or incomplete diagnosis were assumed to be the same. For older, pre-NBS cohorts, cumulative probability of diagnosis by a given age was assumed. All metrics were incorporated into the model to simulate changes in prevalence over time.

RESULTS: The literature review revealed LC-FAOD incidence of approximately 0.002%. In the US in 2020, the model estimated 2,922 patients with LC-FAOD and 2,059 (70.4%) positively diagnosed. The majority (63%) of diagnosed patients would be pediatric due to NBS and premature mortality in adult patients. In 2030, the model projected the population would increase to 3,189 patients, with 2,497 (78.3%) positively diagnosed.

CONCLUSIONS: The present model represents a method of estimating incidence and prevalence of rare diseases where existing research is limited. The primary limitation were limited data inputs, particularly mortality of pre-NBS adults.