Regular Article
Estimated prevalence of moderate to severely elevated total homocysteine levels in the United States: A missed opportunity for diagnosis of homocystinuria?

https://doi.org/10.1016/j.ymgme.2020.02.001Get rights and content
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Highlights

  • Prevalence of homocystinuria (HCU) may be underestimated due to inadequate screening.

  • Patients with elevated homocysteine but no HCU diagnosis display other signs of HCU.

  • Thousands of patients in the US may be living with the sequela of undiagnosed HCU.

  • Intermediate to severely elevated homocysteine may warrant further testing for HCU.

Abstract

Classical homocystinuria (HCU) is a genetic disorder caused by mutations in the cystathionine beta synthase gene, which results in impaired metabolism of the sulfur-bearing amino acid homocysteine and its accumulation in blood and tissues. Classical HCU can be detected via newborn screening in the United States, but the test is widely acknowledged to miss many patients. While severely elevated homocysteine levels (>100 μmol /L) frequently lead to a classical HCU diagnosis, intermediate levels (>30 to 100 μmol /L), though linked to many of the known complications of HCU, are not always recognized as associated with HCU. We aimed to identify and describe potentially undiagnosed classical HCU patients using a nationally-representative database of administrative claims and laboratory results. We estimated the national prevalence of patients with homocysteine >30 μmol /L, and compared their demographic and clinical characteristics to those of patients with homocysteine levels ≤30 μmol/L. Among 57,580 patients with a homocysteine test result, 1.8% had a value >30 μmol /L. Patients with homocysteine >30 μmol /L were more frequently diagnosed with hypothyroidism (39.2% vs. 20.7%, p < .001) and renal disease (9.7% vs. 5.5%, p < .001), and were more likely to have a prescription for an anxiolytic/antidepressant (44.5% vs. 38.9%), opioid (58.4% vs. 53.1%), steroid (46.4% vs. 42.5%), or thyroid hormone (38.8% vs. 18.8%), compared to patients with homocysteine ≤30 μmol /L (all p < .05). Both groups were equally likely to have a diagnosis of homocystinuria or another disorder of sulfur-bearing amino acid metabolism (3.8% vs. 4.0%, p = .752). The age-adjusted national prevalence of homocysteine >30 μmol /L was estimated at 33,068 (95% CI: 1033 - 35,104). These findings suggest that thousands of people in the US may be living with intermediate to severely elevated homocysteine levels and may require further evaluation for the presence of classical HCU.

Abbreviations

CBS
cystathionine beta synthase
HCU
homocystinuria
MTHFR
methylenetetrahydrofolate reductase
tHcy
total homocysteine

Keywords

Homocysteine
Homocystinuria
Hyperhomocysteinemia
Prevalence

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