Epidemiological studies have grown in strength within the last decade or so globally as countries see the benefit of introducing national registries that allow patients of various disease categories to be counted.
In centuries past, when the world was unmapped, and matters of geography, population, and disease prevalence can only be intellectually estimated, there was no ironclad way for clinicians to chart the prevalence of a disease in a given population, as well as its evolution. This was a great disservice to the field of rare diseases, in which the only way for clinician and patient to meet was by word-of-mouth and the willingness of either party to travel over sometimes intolerably long distances.
Nevertheless, countries all around the world are recognizing the importance of tracking the prevalence of even rare diseases in a given population, such as is the case for long chain fatty acid oxidation disorders (LCFAOD). The thrust of the benefits are clinical: epidemiological studies aid in risk assessment, informs diagnostic and treatment decision-making and determines the economic burden of each type of therapy.
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Read more about LCFAOD etiology
“With [epidemiological] data, researchers and clinicians can compare disease rates between different subgroups of people to perform risk assessment analyses, support diagnostic decisions, plan health care needs, evaluate disease burden, and determine the economic benefit of treatment,” Kruger and colleagues wrote in Advances in Therapy.
Among the countless rare diseases that can be investigated, Kruger et al initiated a study on the epidemiology of LCFAOD. LCFAOD is a genetic metabolic disorder in which the transport of fatty acids into the mitochondrion is compromised. The ability of fatty acids to travel into the mitochondria when needed is crucial for the body to meet individual energy demands.
There is a great heterogeneity in terms of the presentation of the typical patient with LCFAOD; symptoms can range from liver dysfunction and renal damage to lethargy and muscle weakness. Some patients are at risk of sudden death. This disease can present itself at any age, but it is most lethal when it occurs shortly after birth.
The Arrival of Newborn Screening
In the late 1990s, newborn screening programs for LCFAOD were initiated. In Genetics in Medicine, Marsden and colleagues wrote about the value of having a newborn screening program for this disease. There is no doubt that the introduction of newborn screening programs for LCFAOD have caused detection rates to increase, both in the United States and in many other countries. Crucially, they contribute to improved outcomes, reducing the rates of symptomatic disease, neurodevelopmental delay, and death.
Of course, like all newborn screening tests, false-negatives and false-positives do occur. Also, newborn screening programs alone neither predict disease outcome nor are they particularly helpful in assisting physicians in determining a personalized treatment plan.
Nevertheless, from an epidemiological perspective, newborn screening programs remain 1 of the best ways to accurately estimate the prevalence of a disease in a given population — after all, unless otherwise stated, newborn screening programs are all for infants, meaning that the disease can be diagnosed early, accurately, and widely. Newborn screening programs contribute significantly to the incidence and prevalence data of a particular disease.
Kruger and colleagues conducted a literature review to estimate the prevalence of LCFAOD by using online academic search engines. One study the research team discovered had a model programmed in Microsoft Excel 2010 to forecast LCFAOD prevalence from incidence-derived prevalence data.
“Incidence-derived prevalence was determined as a combination of calculated incidence based on known sources, population, mortality, and rate of diagnosis at a given time point based on the availability and implementation of diagnostic technology, as well as disease management strategies,” Kruger et al wrote.
Read more about LCFAOD treatment
Based on the literature review conducted by Kruger and colleagues, they estimated that there were approximately 2871 cases of LCFAOD in the United States in 2021—1355 were children and 1515 were adults. Compared to the estimated 330 million individuals living in the United States, this figure represents a drop in the bucket.
The Microsoft Excel-derived model predicts that there will be 3425 cases of LCFAOD in the United States in 2040—1452 pediatric cases and 1973 adult cases, a minimal increase at best.
It is perhaps interesting to note that nowhere in medical literature has a true mortality rate been determined for LCFAOD since it is exceedingly rare, has various ages of onset, and different methods of sampling. Nevertheless, the model described in this study estimates that mortality rate is decreasing, meaning that more patients with LCFAOD are surviving into adulthood. This is evidence that early diagnosis is making a notable impact; the downside is that clinicians may not be fully equipped to handle a new wave of young patients with LCFAOD transitioning into adulthood.
Future Research Needed
From this study, we can draw a few conclusions: first, LCFAOD remains exceedingly rare in the United States; second, prognosis is improving. Ultimately, the best way to manage patients with LCFAOD is via early diagnosis and the early initiation of a management plan — 1 of the best arguments for the continued implementation of newborn screening programs. At the same time, we must be mindful that an inevitable population of patients exist who remain undiagnosed until the disease has become advanced.
“Together, these observations emphasize the need for further research on LCFAOD, particularly surrounding mortality and the impact of treatment on outcomes in these patients,” the authors of the study reflected.
References
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
Marsden D, Bedrosian CL, Vockley J. Impact of newborn screening on the reported incidence and clinical outcomes associated with medium- and long-chain fatty acid oxidation disorders. Genet Med. Published online December 7, 2020. doi:10.1038/s41436-020-01070-0
