High clinical burden of classical homocystinuria in the United States: a retrospective analysis
Abstract Background Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden...
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BMC
2025-01-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03530-9 |
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| author | Mahim Jain Mehul Shah Kamlesh M. Thakker Andrew Rava Agnes Pelts Block Colette Ndiba-Markey Lionel Pinto |
| author_facet | Mahim Jain Mehul Shah Kamlesh M. Thakker Andrew Rava Agnes Pelts Block Colette Ndiba-Markey Lionel Pinto |
| author_sort | Mahim Jain |
| collection | DOAJ |
| description | Abstract Background Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden of patients with HCU, especially stratified by total homocysteine (tHcy) levels. This study aimed to describe the overall clinical burden of patients with HCU in the United States and key clinical events by tHcy levels using administrative claims data. Methods This non-interventional retrospective cohort analysis from January 01, 2016, through September 30, 2021, used Optum’s de-identified Market Clarity Data. Patients who had 1 or more International Classification of Diseases, Tenth Revision code for homocystinuria (E72.11) or the signs, disease, and symptoms term homocystinuria in the natural language processing dataset were included. To obtain a study population most likely to have HCU, stratifications by tHcy levels, clinical characteristics, and phenotypic expressions were applied to refine the cohort. Included patients were then stratified by highest tHcy level. Clinical burden was measured by category of HCU-related events. Descriptive statistics were reported. Results Six hundred thirty-three patients met the inclusion criteria, and 601 patients had a tHcy level: < 50 µM (n = 278), 50 to < 100 µM (n = 212), and ≥ 100 µM (n = 111). Among the 601 patients with a tHcy level, almost one-half (n = 297, 49.4%) had at least one thrombotic/thromboembolic, skeletal, ocular, or neurological event and 14.1% (n = 85) had multiple events. Thrombotic/thromboembolic events (n = 186, 30.9%) were the most common type of events, followed by skeletal (n = 100, 16.6%), ocular (n = 63, 10.5%), and neurological events (n = 50, 8.3%). During follow-up, 5.7% (n = 34) of the patients died. All events assessed were more prevalent in the 50 to < 100 µM group and ≥ 100 µM group compared with those in the < 50 µM group. Conclusions As has been believed, patients with tHcy ≥ 100 µM carried a substantial clinical burden, but the burden is also very high in those whose levels were ≥ 50 µM. Thrombotic/thromboembolic events were more common than skeletal, ocular, or neurological events. Meaningfully lowered tHcy levels may help to reduce significant clinical events. |
| format | Article |
| id | doaj-art-50abc3cd7f8546269d3b021cd1c506dd |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-50abc3cd7f8546269d3b021cd1c506dd2025-01-26T12:52:21ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-0120111210.1186/s13023-025-03530-9High clinical burden of classical homocystinuria in the United States: a retrospective analysisMahim Jain0Mehul Shah1Kamlesh M. Thakker2Andrew Rava3Agnes Pelts Block4Colette Ndiba-Markey5Lionel Pinto6Kennedy Krieger Institute, Johns Hopkins MedicineTravere Therapeutics, Inc.Notting Hill Consulting LLCGenesis Research GroupTravere Therapeutics, Inc.Genesis Research GroupTravere Therapeutics, Inc.Abstract Background Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden of patients with HCU, especially stratified by total homocysteine (tHcy) levels. This study aimed to describe the overall clinical burden of patients with HCU in the United States and key clinical events by tHcy levels using administrative claims data. Methods This non-interventional retrospective cohort analysis from January 01, 2016, through September 30, 2021, used Optum’s de-identified Market Clarity Data. Patients who had 1 or more International Classification of Diseases, Tenth Revision code for homocystinuria (E72.11) or the signs, disease, and symptoms term homocystinuria in the natural language processing dataset were included. To obtain a study population most likely to have HCU, stratifications by tHcy levels, clinical characteristics, and phenotypic expressions were applied to refine the cohort. Included patients were then stratified by highest tHcy level. Clinical burden was measured by category of HCU-related events. Descriptive statistics were reported. Results Six hundred thirty-three patients met the inclusion criteria, and 601 patients had a tHcy level: < 50 µM (n = 278), 50 to < 100 µM (n = 212), and ≥ 100 µM (n = 111). Among the 601 patients with a tHcy level, almost one-half (n = 297, 49.4%) had at least one thrombotic/thromboembolic, skeletal, ocular, or neurological event and 14.1% (n = 85) had multiple events. Thrombotic/thromboembolic events (n = 186, 30.9%) were the most common type of events, followed by skeletal (n = 100, 16.6%), ocular (n = 63, 10.5%), and neurological events (n = 50, 8.3%). During follow-up, 5.7% (n = 34) of the patients died. All events assessed were more prevalent in the 50 to < 100 µM group and ≥ 100 µM group compared with those in the < 50 µM group. Conclusions As has been believed, patients with tHcy ≥ 100 µM carried a substantial clinical burden, but the burden is also very high in those whose levels were ≥ 50 µM. Thrombotic/thromboembolic events were more common than skeletal, ocular, or neurological events. Meaningfully lowered tHcy levels may help to reduce significant clinical events.https://doi.org/10.1186/s13023-025-03530-9Classical homocystinuriaTotal homocysteineClinical burden |
| spellingShingle | Mahim Jain Mehul Shah Kamlesh M. Thakker Andrew Rava Agnes Pelts Block Colette Ndiba-Markey Lionel Pinto High clinical burden of classical homocystinuria in the United States: a retrospective analysis Orphanet Journal of Rare Diseases Classical homocystinuria Total homocysteine Clinical burden |
| title | High clinical burden of classical homocystinuria in the United States: a retrospective analysis |
| title_full | High clinical burden of classical homocystinuria in the United States: a retrospective analysis |
| title_fullStr | High clinical burden of classical homocystinuria in the United States: a retrospective analysis |
| title_full_unstemmed | High clinical burden of classical homocystinuria in the United States: a retrospective analysis |
| title_short | High clinical burden of classical homocystinuria in the United States: a retrospective analysis |
| title_sort | high clinical burden of classical homocystinuria in the united states a retrospective analysis |
| topic | Classical homocystinuria Total homocysteine Clinical burden |
| url | https://doi.org/10.1186/s13023-025-03530-9 |
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