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Homozygous antithrombin deficiency type II (99 Leu to Phe mutation) and childhood thromboembolism
S Kuhle1, D A Lane, K Jochmanns
1Dept. of Paediatrics, Vienna University Hospital, Austria.
Insights
Homozygous antithrombin deficiency type II can cause severe thromboembolic events in children, even from one week of age. Genetic analysis is crucial for early diagnosis and management of this rare bleeding disorder.
Area of Science:
- Medical Genetics
- Hematology
- Thrombosis Research
Background:
- Antithrombin deficiency is a rare genetic disorder that increases the risk of blood clots.
- Type II deficiency specifically affects the heparin-binding site of antithrombin.
- Homozygous deficiency is extremely rare and less understood than heterozygous forms.
Observation:
- The study identified 5 children from 3 families with homozygous antithrombin deficiency type II (99 Leu to Phe mutation).
- Four children experienced severe, spontaneous thromboembolic events, including deep vein thrombosis, caval vein thrombosis, and ischemic stroke, at various ages from one week to 14 years.
- One 17-year-old male patient with the same genetic mutation remained asymptomatic.
Findings:
- Homozygous antithrombin deficiency type II can manifest with severe clinical symptoms early in life.
- The specific mutation (99 Leu to Phe) impacts the heparin-binding site, leading to thrombotic events.
- Asymptomatic presentation is possible despite homozygous deficiency, highlighting variability in disease expression.
Implications:
- Early and accurate diagnosis of homozygous antithrombin deficiency is critical for preventing severe thrombotic events.
- Genetic analysis is essential for confirming the diagnosis in suspected cases.
- Long-term oral anticoagulation therapy should be considered for individuals diagnosed with this condition to mitigate thrombosis risk.
Abstract:
We report 5 children from 3 families with homozygous antithrombin deficiency type II affecting the heparin binding site (99 Leu to Phe mutation). Four children had severe spontaneous thromboembolic events (deep leg or caval vein thrombosis, ischaemic stroke) at one week, 3 months, 13 and 14 years of age. The fifth patient, a 17 year-old boy was asymptomatic. Early manifestation of homozygous deficiency calls for prompt and accurate diagnosis. In doubtful cases genetic analysis is required. Long-term oral anticoagulation should be considered in affected individuals.