Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison

Abstract

Background: 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). 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).Methods: Patients 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. Results: Patients 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.(Continued on next page)

Case report: Spontaneous bilateral intraocular lens dislocation in a patient with homocystinuria

“…It is diagnosed by elevated plasma total homocysteine concentration ( 7 ). Clinically, it is characterized by ocular disorders, skeletal abnormalities, developmental delays, and thromboembolic events ( 3 ).…”

“…Homocystinuria is a rare autosomal recessive disease mainly caused by the absence of cystathionine-β-synthase, which is involved in the methionine metabolism pathway, affecting 0.82 in 100,000 the population worldwide ( 1 , 2 ). Untreated cases result in multisystemic disorders, including ocular diseases, skeletal abnormalities, developmental delay, and thromboembolic events ( 3 ).…”

Allelic Prevalence and Geographic Distribution of Cerebrotendinous Xanthomatosis

“…We underscore the value of leveraging large and diversi ed population-based genetic databases to assess risk for inherited diseases. Such efforts, cross-referenced with other large-scale programs, such as newborn screening [19] and retrospective administrative claims studies [49], may provide the most accurate strategy to assess disease presence in a population. In turn, this will translate into greater awareness, better recognition, and early treatment intervention, which will directly bene t patients and caretakers.…”

Classic homocystinuria: etiology, natural history and treatment

“…Например, в Катаре она достигла 1:1800 [14]. В США предполагаемая распространенность классической гомоцистинурии составляет 1 : 100 000-200 000, хотя результаты недавно опубликованного исследования свидетельствуют о том, что фактически она по крайней мере в 10 раз выше и может достигать 1 : 10 000 [15]. Классическую гомоцистинурию обычно диагностируют педиатры на основании типичных клинических проявлений и результатов лабораторных исследований, в частности повышения уровня гомоцистеина в крови.…”