Ann Hematol (2003) 82:178–180 DOI 10.1007/s00277-002-0596-7 CASE REPORT M. Gupta · S. Gupta · R. Saxena · R. Ahmed · V. P. Choudhry Familial hyperhomocysteinemia: multiple venous thrombosis in four generations of a family Received: 24 June 2002 / Accepted: 9 November 2002 / Published online: 1 February 2003  Springer-Verlag 2003 Abstract We describe a family in which four generations (eight members) had deep vein thrombosis of the lower limb and three of the alive members had documented hyperhomocysteinemia. In addition, one of the family members had evidence of arterial thrombosis in the form of cerebral infarcts. Interestingly, all affected members in the family were males. Keywords Hyperhomocysteinemia · Venous thrombosis Introduction The association between moderate hyperhomocysteine- mia and venous thrombosis is known. Although mild hyperhomocysteinemia often occurs within families, thus far no direct association between venous thromboembo- lism and specific mutations that cause hyperhomocys- teinemia have been reported. Several case control studies that used thrombosis-free population-based controls have demonstrated an association between mildly elevated levels of homocysteine and venous thromboembolism. However, no family studies have been reported for hyperhomocysteinemia. Here we describe an interesting family in which four generations (eight members) of the family had either documented or suspected deep vein thrombosis and three of the alive members had documented hyperhomocys- teinemia. One of the family members had evidence of arterial thrombosis also in the form of cerebral infarcts. Interestingly, all eight affected family members were males. None of the females in the entire family were symptomatic. Case report The index case was a 32-year-old man with swelling and pain of the left leg for the last 2 years. His history dated back to 2 years when he met with a roadside accident and suffered a fracture of the right tibia. He had a plaster cast for 3 months. The swelling and pain in his left leg had been waxing and waning since then. He also noted bluish discoloration of his left ankle 1.5 years later. There was no history of swelling and pain in the right leg and upper limbs. There was no history of prominence of veins, ulcer formation, loss of sensation, and claudication in the lower limbs. There was no past history of diminution of vision, syncopal attacks, respiratory distress, chest or abdominal pain. The patient had not taken any medications for his illness. He was nonhypertensive, nondiabetic, and a nonsmoker. He had a significant family history. His father and one of his paternal cousins had suspected deep vein thrombosis of the lower extremities. Their problem also started after prolonged immobili- zation following roadside accidents. Apart from these three, the other family members who are/were affected include the great- grandfather, grandfather, two of his father’s brothers, and another paternal cousin who additionally had multiple cerebral infarcts and expired 6 months previously. None of the females in the entire family was affected (family pedigree is shown in Fig. 1). M. Gupta · S. Gupta · R. Saxena ( ) ) · R. Ahmed · V. P. Choudhry Department of Haematology, All India Institute of Medical Sciences, IRCH building 1st floor, Ansari Nagar, AIIMS, 110029 New Delhi, India e-mail: renusax@hotmail.com Tel.: +91-11-6864851 ext. 3642 Fax: +91-11-6862663 Fig. 1 Family pedigree