Summary Reduced bone mineral density (BMD) in childhood is a risk factor for osteoporosis in later life. This case–control study determined the prevalence of low BMD, calcium intake and physical activity in 62 haemophilic children and 62 sex‐, race‐ and age‐matched healthy boys as controls. Lumbar spine (L2‐L4) BMD was determined by dual‐energy X‐ray absorptiometry; BMD was considered to be low when Z‐score ≥2. Physical activity was assessed using a validated questionnaire and calcium intake with a standardized quantitative food frequency questionnaire. Twenty‐four patients (38%) had low BMD, whereas this was found in only 10 (16%) controls [odds ratio (OR) 2·86, 95% confidence interval (CI) 1·17–7·41; P = 0·014]. Lumbar BMD was significantly lower in the haemophilia patients than the controls (−1·6 ± 1·0 vs. −0·9 ± 0·9 respectively; P = 0·0004). Sedentary and low‐grade exercise predominated in haemophilia (77%) versus control (50%) (OR 3·2, 95% CI 1·36–7·79; P = 0·003). There were no differences between groups with regard to calcium intake. Our results suggest that low‐physical activity is a risk factor for reduced lumbar bone mass in the haemophilic group. This factor must be monitored to avoid a significant reduction in BMD that might contribute to further skeletal fragility.

Hemophilia A (HA) is one of the most common inherited bleeding disorders caused by FVIII gene mutations. Inversion of intron 22 (inv22) originates 50% of cases of severe HA and is a major risk factor for inhibitor development. Inversion of intron 1 (inv1) has been reported to occur in 2-3% of severe HA patients. We studied both inversions to determine their frequencies in Mexican patients with severe HA and to compare these data with other HA populations. The inv22 was evaluated as a risk factor for FVIII inhibitor development in severe HA patients. We studied 44 patients from 31 severe HA families for the detection of inv22 and 94 patients from 65 families to detect inv1. We used the subcycling long-distance PCR to detect inv22 and rapid PCR in duplex reactions to detect inv1. We found a frequency of 45% for the inv22 and no inv1-positive patients (0%). These frequencies were not statistically different from other populations, although haplotype analyses of FVIII gene and telomeric regions should be incorporated to explore population-specific variation of inv1 frequencies. Inv22-positive patients showed 1.88X higher risk for developing inhibitors with respect to patients carrying other severe mutations; however, this OR value was not significant. Our findings confirm inv22 as a hot-spot for severe HA and evidence the low frequency of inv1 in a Mexican population. The non-significant risk for developing inhibitors among inv22-positive patients agrees with the variety of genetic and non-genetic factors involved in such a complication. Am. J. Hematol. 82:283-287, 2007. V V C 2007 Wiley-Liss, Inc.

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A semi-quantitative expression analysis of both AML1-a and AML1-total was performed by RT-PCR in 19 children with acute lymphoblastic leukemia (ALL) at diagnosis. AML1-a expression was assessed in 16 bone marrow (BM) and 13 peripheral blood (PB) samples whereas AML1-total was assessed in 17 BM and 16 PB samples. These analyses were also carried out in 15 PB samples of healthy controls. In addition, 18/19 patients were karyotyped: 11 had an unmodified constitutional karyotype (CK) and seven exhibited acquired chromosomal abnormalities (ACA). The expression of AML1-a was significantly increased in BM and PB when compared with the controls (p < 0.013 and p < 0.035, respectively). A significant increase was found in the expression of AML1-a in BM of the ACA group compared with the CK group (p < 0.0009). The expression of AML1-a in BM and PB showed a significant increase in the ACA group compared with controls (p < 0.00001 and p < 0.012, respectively); in contrast, the CK group did not differ from the controls. These observations may mean that the increase of AML1-a favours the progression of leukemia.

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