A modeling methodology for estimating the prevalence of rare diseases has been proposed and demonstrated for long chain fatty acid oxidation disorder (LCFAOD).

The proposed model, published in Advances in Therapy, utilizes newborn screening reports and applies them to key modifiers. The modifiers include changes in population growth over time and variable standardization rates of the disease screening that lead to a confirmed diagnosis or improvements in standards of care and survival estimates.

“Although each rare disease is unique, the approach described here and demonstrated in the estimation of LCFAOD prevalence provides the necessary tools to calculate key epidemiological estimates useful in performing risk assessment analyses,” the authors said.

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Using the model, the authors estimated the current prevalence of LCFAOD at 2871 cases in the US in 2021 with 1355 being in children and 1515 being adults. The overall diagnostic rate was estimated to be 72%.

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The prevalence estimate varied depending on the year 1990, the year that LCFAOD was introduced to newborn screening panels, having a prevalence of 2030 cases with 43% being pediatric and 57% being adults. The estimated diagnosis rate was much lower in 1990 as well being only 39%. Using the model to predict future prevalence, 3425 cases are predicted for the year 2040. 

Applying the model to global prevalence estimated 56,245 cases in 1990 which increased to 82,333 cases in 2021. The forecast for 2040 yielded an estimate of 95,457 global cases.

The estimates were calculated using incidence data, diagnostic rate, population changes, and mortality information. From literature sources, the global incidence rate for LCFAOD was estimated to be 200 per 100,000 births (0.0020%). Diagnostic rates differed before and after the initialization of newborn screening and values were based on clinical expertise, the current standard of care, and the intensity of disease presentation.

No true mortality rate has been established for LCFAOD in the literature due to high variability based on the age of onset, symptoms, age at diagnosis, and differences in sampling. For the mortality rate used in the model, the survival curve for the general population was applied with modifications of excess mortality added ranging from an extra 10.0% for undiagnosed patients with the most intense symptoms down to 0.0% for asymptomatic patients with an early diagnosis.


Kruger E, McNiven P, Marsden D. Estimating the prevalence of rare diseases: long-chain fatty acid oxidation disorders as an illustrative example. Adv Ther. Published online June 8, 2022. doi:10.1007/s12325-022-02186-2