Inactivity is a risk factor for low bone mineral density among haemophilic children.

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 > or =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.

Frequency of intron 1 and 22 inversions of Factor VIII gene in Mexican patients with severe hemophilia A.

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.

Molecular spectrum of beta-thalassemia in the Mexican population.

Beta-thalassemia (beta-thal) is present in 59% and 75% of patients with abnormal hemoglobin disorders in northwestern and central Mexico, respectively. In our Research Center, up until 1997, we reported the presence of 13 beta-thal alleles in 26 unrelated chromosomes (-28A>C; -87C>T; MET1VAL; IVS1, G>A, +1; IVS1, G>A, +5; IVS1, G>C, +5; IVS1, G>A, +110; IVS2, C>G, +745; GLU6FS; VAL11FS; GLN39TER; HBD/HBB 104 kb del; and HBD87/HBB116 fusion). Since then, 57 more beta-thal chromosomes have been identified by the amplification-refractory mutation system (ARMS) and DNA sequencing from 54 individuals with beta-thalassemia (seven compound heterozygotes, three with two beta-thal alleles, three with beta-thal and HbS, and one with beta-thal and HbD; and 47 beta-thal heterozygotes). Nine of the previously observed alleles were found, together with three new alleles: IVS2, G>A, +1; LYS17TER; and 4-bp del, 41/42CTTT. Moreover, a novel mutation was observed, HIS77FS, bringing to a total of 17 beta-thal alleles identified in our population. Six alleles constitute 78.3% of the observed alleles: five Mediterranean alleles (GLN39TER; IVS1, G>A, +1; IVS1, G>A, +110; HBD/HBB 104 kb del; and IVS1, G>A, +5) and one common in the Kurdish population (-28A>C). We note especially the presence in these families of -28A>C and VAL11FS, both of which have previously been considered private alleles. The observed spectrum of mutations is characteristic of populations with low frequencies of thalassemias. Because thalassemia is not a rare disease in Mexico, we emphasize its necessary consideration in the differential diagnosis of microcytic hypochromic anemia.

Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants.

Screening for mutations at the G-6-PD gene by PCR-SSCP combined with restriction enzyme analysis and DNA sequencing was performed in nine G-6-PD deficient individuals with negative results for the presence of the most frequent G-6-PD mutations previously observed in Mexican population. The variants G-6-PD Valladolid(406T), G-6-PD Durham(713G), and G-6-PD Viangchan(871A) and four new G-6-PD mutant alleles were identified. The new mutations are located at cDNA nt 376 A --> T (126 Asn --> Tyr), nt 770 G --> T (257 Arg --> Leu), nt 1094 G --> A (365 Arg --> His), and nt 1285 A --> G (429 Lys --> Glu) and they were named G-6-PD San Luis Potosi, G-6-PD Zacatecas, G-6-PD Veracruz, and G-6-PD Yucatán, respectively. To date, a total of 18 different G-6-PD variants have been observed in Mexico and several of them are common in Africa, South Europe, and Southeast Asia.

Eritrocitos micronucleados en niños esplenectomizados con y sin quimioterapia / Micronucleated erytrocytes in splenectomized children with or without antineoplastic chemotherapy

Introducción. En el ser humano el bazo elimina de la circulación eritrocitos micronucleados (EMN) entre otras anormalidades; después de la esplenectomía, estos se evidencia, y al recibir quimioterapia antineoplásica (QA) se incrementa. El objetivo de este trabajo fue comparar el número de EMN en sangre periférica de niños esplenectomizados con y sin QA. Material y métodos. Se colectaron 56 muestras de 42 pacientes del Departamento de Hematología de Pediatria del Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, las cuales fueron divididas en 4 grupos (grupo 1: paciente con bazo y sin QA, grupo 2: paciente con bazo y con QA; grupo 3: pacientes esplenectomizados y sin QA; y grupo 4: pacientes esplenectomizados y con QA). Se realizaron frotis de sangre periférica; se tiñeron (tinción de Wright y Giemsa) y contaron al microscopio los EMN en 10,000 eritrocitos totales. Resultados. Se observó diferencia entre esplenectomizados vs no esplenectomizados (P<0.001); no así en el grupo no esplenectomizado con y sin QA. Al compara el grupo esplenectomizado sin QA vs con QA, se encontró diferencia significativa (P< 0.001). El número de EMN en niños resultó más bajo (P< 0.001) al compararlos con datos previos de adultos. Conclusión. Estos resultados revelan que el niño esplenectomizado es un bioindicador de agentes genotóxicos