OBJECTIVES: Long-chain fatty acid oxidation disorders (LC-FAOD) are 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. Many countries have introduced NBS for LC-FAOD, which has increased diagnosis rates and reduced mortality rates, whereas some countries have no screening for LC-FAOD. This study describes an epidemiological model developed to estimate overall prevalence of LC-FAOD and reports results for 5 countries - Germany, Italy, Spain, United Kingdom (UK), and France.

METHODS: A targeted literature review identified studies reporting LC-FAOD incidence, NBS, prevalence, morbidities, 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 data, diagnostic criteria, rates of misdiagnosis, delayed diagnosis, or incomplete diagnosis were assumed the same. For countries without NBS and older, pre-NBS cohorts, cumulative probability of diagnosis by a given age was assumed. All metrics were incorporated into the MS Excel model to simulate changes in prevalence over time.

RESULTS: Literature review revealed LC-FAOD incidence of ~0.002%. In 2020, the model predicted 546 (68% diagnosed), 387 (53%), 296 (50%), 471 (49%), and 476 (49%) patients for Germany, Italy, Spain, UK and France respectively. Germany and Italy have 100% NBS, UK and France have no NBS and Spain has variation across regions.

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 patients with LC-FAOD identified symptomatically.