Allelic background of LEPRE1 mutations that cause recessive forms of osteogenesis imperfecta in different populations.

Biallelic mutations in LEPRE1 result in recessively inherited forms of osteogenesis imperfecta (OI) that are often lethal in the perinatal period. A mutation (c.1080+1G>T, IVS5+1G>T) in African Americans has a carrier frequency of about 1/240. The mutant allele originated in West Africa in tribes of Ghana and Nigeria where the carrier frequencies are 2% and 5%. By examining 200 samples from an African-derived population in Tobago and reviewing hospital neonatal death records, we determined that the carrier frequency of c.1080+1G>T was about one in 200 and did not contribute to the neonatal deaths recorded over a 3-year period of time in Trinidad. In the course of sequence analysis, we found surprisingly high LEPRE1 allelic diversity in the Tobago DNA samples in which there were 11 alleles distinguished by a single basepair variant in or near exon 5. All the alleles found in the Tobago population that were within the sequence analysis region were found in the African American population in the Exome Variant Project. This diversity appeared to reflect the geographic origin of the original population in Tobago. In 44 individuals with biallelic LEPRE1 mutations identified by clinical diagnostic testing, we found the sequence alterations occurred on seven of the 11 variant alleles. All but one of the mutations identified resulted in mRNA or protein instability for the majority of the transcripts from the altered allele. These findings suggest that the milder end of the clinical spectrum could be due to as yet unidentified missense mutations in LEPRE1.

Anaemia and kidney dysfunction in Caribbean type 2 diabetic patients.

BACKGROUND: Anaemia has been shown in previous studies to be a risk factor for cardiovascular disease in diabetic patients with chronic kidney disorder. This study was aimed to assess the prevalence of anaemia and kidney dysfunction in Caribbean type 2 diabetic patients that have been previously shown to have a high prevalence of the metabolic syndrome. METHODS: 155 type 2 diabetic patients and 51 non-diabetic subjects of African origin were studied. Anthropometric parameters were measured and fasting blood samples were collected for glucose, creatinine, glycated hemoglobin and complete blood count. Anaemia was defined as haemoglobin < 12 g/dl (F) or < 13 g/dl (M). Kidney function was assessed using glomerular filtration rate (GFR) as estimated by the four-variable Modification of Diet in Renal Disease (MDRD) study equation. Subjects were considered to have chronic kidney disease when the estimated GFR was < 60 ml/min per 1.73 m2. Comparisons for within- and between-gender, between diabetic and non-diabetic subjects were performed using Student's t-test while chi-square test was employed for categorical variables. RESULTS: The diabetic patients were older than the non-diabetic subjects. While male non-diabetic subjects had significantly higher red blood cell count (RBC), haemoglobin and hematocrit concentrations than non-diabetic female subjects (p < 0.001), the RBC and hematocrit concentrations were similar in male and female diabetic patients. Furthermore, irrespective of gender, diabetic patients had significantly higher prevalence rate of anemia than non-diabetic subjects (p < 0.05). Anaemic diabetes patients had significantly lower GFR (67.1 +/- 3.0 vs. 87.9 +/- 5.4 ml/min per 1.73 m2, p < 0.001) than non-anaemic patients. CONCLUSION: A high prevalence of anaemia was identified in this group of type 2 diabetic patients previously shown to have a high prevalence of the metabolic syndrome. It is therefore recommended that diagnostic laboratories in developing countries and elsewhere should include complete blood count in routine laboratory investigations in the management of diabetic patients.

Anaemia and kidney dysfunction in Caribbean type 2 diabetic patients.

BACKGROUND: Anaemia has been shown in previous studies to be a risk factor for cardiovascular disease in diabetic patients with chronic kidney disorder. This study was aimed to assess the prevalence of anaemia and kidney dysfunction in Caribbean type 2 diabetic patients that have been previously shown to have a high prevalence of the metabolic syndrome. METHODS: 155 type 2 diabetic patients and 51 non-diabetic subjects of African origin were studied. Anthropometric parameters were measured and fasting blood samples were collected for glucose, creatinine, glycated hemoglobin and complete blood count. Anaemia was defined as haemoglobin < 12 g/dl (F) or < 13 g/dl (M). Kidney function was assessed using glomerular filtration rate (GFR) as estimated by the four-variable Modification of Diet in Renal Disease (MDRD) study equation. Subjects were considered to have chronic kidney disease when the estimated GFR was < 60 ml/min per 1.73 m2. Comparisons for within- and between-gender, between diabetic and non-diabetic subjects were performed using Student's t-test while chi-square test was employed for categorical variables. RESULTS: The diabetic patients were older than the non-diabetic subjects. While male non-diabetic subjects had significantly higher red blood cell count (RBC), haemoglobin and hematocrit concentrations than non-diabetic female subjects (p < 0.001), the RBC and hematocrit concentrations were similar in male and female diabetic patients. Furthermore, irrespective of gender, diabetic patients had significantly higher prevalence rate of anemia than non-diabetic subjects (p < 0.05). Anaemic diabetes patients had significantly lower GFR (67.1 +/- 3.0 vs. 87.9 +/- 5.4 ml/min per 1.73 m2, p < 0.001) than non-anaemic patients. CONCLUSION: A high prevalence of anaemia was identified in this group of type 2 diabetic patients previously shown to have a high prevalence of the metabolic syndrome.

Beta-globin gene cluster haplotypes and alpha-thalassemia in sickle cell disease patients from Trinidad.

In this study, we have determined the frequency of beta(S) haplotypes in 163 sickle cell disease patients from Trinidad. The alpha(3.7) globin gene deletion status was also studied with an observed gene frequency of 0.17. Among the 283 beta(S) chromosomes analyzed, the Benin haplotype was the most prevalent (61.8%) followed by Bantu (17.3%), Senegal (8.5%), Cameroon (3.5%), and Arab-Indian (3.2%), while 5.7% of them were atypical. This beta(S) haplotypes distribution differed from those previously described in other Caribbean islands (Jamaica, Guadeloupe, and Cuba), in agreement with the known involvement of the major colonial powers (Spain, France, and Great Britain) in the slave trade in Trinidad and documented an Indian origin of the beta(S) gene.

Severe aplastic anaemia - complete response to antilymphocyte globulin and cyclosporin

Severe aplastic anaemia is uniformly fatal unless treated with immunosuppressive therapy or bone marrow transplantation. The latter is curative in 65 percent of patients and is the treatment of choice in children and young adults. Antilymphocyte globulin (ALG) and cyclosporin may be used successfully in the absence of an HLA matched sibling donor. We report the case of a twelve year old boy with severe aplastic anaemia who received immunosuppressive with ALG and cyclosporin and is alive and well three years an six months post treatment.(AU)

Pre-operative autologous blood donations: a five year experience in Trinidad and Tobago

A pre-operative autologous blood donation programme was started in 1988 and made available to all doctors offering elective surgical procedures. Two hundred and seventy-seven (277) patients presented for autologous donation over a five-year period. Nine point four per cent were rejected because of low haemoglobin (<10.5 g/dl). The single biggest user of the programme was the Princess Elizabeth Hospital for handicapped persons. Patients undergoing orthopaedic procedures gave 50 per cent of the donations, and ranged in age from 10 to 73 years. The oldest donor was a 73-year-old man who had an abdominal aortic aneurysm replaced. Gynaecological surgeons in the public and private sectors together provided 43.9 percent of donors, 3.6 percent of these underwent elective Caesarean Section, each donating one unit of blood at 36 weeks. Patients undergoing general surgical procedures comprised 10.4 percent of donors. Autologous donors contributed 1.3 percent of the total number of donations over this period (AU)

Pre-operative autologous blood donations: a five year experience in Trinidad and Tobago

A pre-operative autologous blood donation programme was started in 1988 and made available to all doctors offering elective surgical procedures. Two hundred and seventy-seven (277) patients presented for autologous donation over a five-year period. Nine point four per cent were rejected because of low haemoglobin (<10.5 g/dl). The single biggest user of the programme was the Princess Elizabeth Hospital for handicapped persons. Patients undergoing orthopaedic procedures gave 50 per cent of the donations, and ranged in age from 10 to 73 years. The oldest donor was a 73-year-old man who had an abdominal aortic aneurysm replaced. Gynaecological surgeons in the public and private sectors together provided 43.9 percent of donors, 3.6 percent of these underwent elective Caesarean Section, each donating one unit of blood at 36 weeks. Patients undergoing general surgical procedures comprised 10.4 percent of donors. Autologous donors contributed 1.3 percent of the total number of donations over this period