Abstract
BackgroundClassical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000–200,000 people in the United States (US). HCU is poorly detected by newborn screening, resulting in underestimates of its prevalence. This study compared characteristics, healthcare use and costs, and projected prevalence between patients with diagnosed HCU, elevated total homocysteine (tHcy), and diagnosed phenylketonuria (PKU).MethodsPatients in the MarketScan® Research Databases were identified with strictly-defined HCU (> 2 diagnoses, including 1 ICD-10), broadly-defined HCU (> 1 ICD-10), elevated tHcy (> 20 μmol/L) without an HCU diagnosis, or > 1 ICD-9/ICD-10 PKU diagnosis during 1/1/2010–12/31/2016 (first qualifying claim = index). Demographics and healthcare utilization and costs per patient per month (PPPM) were compared between all cohorts, frequencies of comorbidities and medications were compared between HCU and elevated tHcy patients, and healthcare provider types were assessed among HCU patients. The prevalence of patients meeting each cohort definition was projected to the United States (US) population.ResultsPatients with strictly-defined (N = 2450) and broadly-defined (N = 6613) HCU, and with elevated tHcy (N = 2017), were significantly older than PKU patients (N = 5120) (57 vs. 56 vs. 53 vs. 18 years; p < 0.05). Vitamin D deficiency, hyperlipidemia, folic acid/B vitamins, and lipid-lowering medications, among others, were more common among diagnosed HCU patients vs. those with elevated tHcy (all p < 0.05). Rates of healthcare utilization were generally higher among HCU and elevated tHcy patients, compared to PKU, though total healthcare costs were similar between groups. Most HCU patients (~ 38%) received their index diagnosis from a primary care physician; very few (~ 1%) had any claim from a geneticist during their enrollment. The age-adjusted national prevalence of HCU was projected at 31,162 (95% CI: 30,411 – 31,913; ~ 1 in 10,000 of the US population) using the broad definition.ConclusionsThe actual prevalence of HCU may be > 10 times prior estimates, at 1 in 10,000 in the US, and this study suggests that HCU is not being diagnosed until later in life. Improvements to newborn screening, detection in young children, and physician education regarding HCU among patients may be necessary to alleviate the burden of this genetic disease.
Highlights
Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000–200,000 people in the United States (US)
Patient selection Out of 100.5 million patients in the Commercial and Medicare databases during the study period, a total of 2450 patients met the criteria for the strictly-defined HCU cohort (> 2 HCU diagnoses, > 1 of these diagnosis being an International classification of diseases (ICD)-10 diagnosis) and an additional 4163 patients had only 1 claim with an HCU diagnosis and that claim had to be an ICD-10 diagnosis
Over 96% of the patients in the Lab Database with an elevated total homocysteine (tHcy) test result had no claims with an ICD-9 or ICD-10 HCU diagnosis during that time period (n = 2017), and these are the patients that comprised the cohort of patients with elevated tHcy without an HCU diagnosis
Summary
Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000–200,000 people in the United States (US). Published literature previously estimated the prevalence of HCU to be approximately 1 in 200,000–335,000 worldwide, and 1 in 100,000–200,000 in the United States (US) [4–6]. These estimates were largely based on patients seen by metabolic geneticists and diagnosed by newborn screening. The preferred newborn screening technique for HCU used in the US has poor sensitivity, as it tests for the precursor amino acid methionine rather than homocysteine. Many patients are not diagnosed until they present with clinical events later in life (ocular disorders, developmental delays, or cardiovascular events including strokes, pulmonary embolism, and myocardial infarction at a young age), and some are likely never diagnosed [6]
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