Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3 gene; first reported case from Botswana.

Huntington's disease-like 2 (HDL2) is a rare autosomal dominant progressive neurodegenerative disorder commonly seen in adults. It was first described in a large African-American family in the United States. HDL2 clinically resembles Huntington's disease (HD) and causes adult-onset relentlessly progressive movement, emotional and cognitive dysfunction. Onset is usually in the fourth decade with slow progression to death. We present a 47-year-old male Botswana native, with a four-year-history of chorea, slurred speech, mood instability, cognitive impairment and weight loss. Genetic testing reveals normal HTT gene but a heterozygous expansion mutation at the JPH3 locus, confirmatory of HDL2. Though some cases of HDL2 have been reported from neighboring South Africa, this is the first instance from Botswana. This report draws attention to the fact that HDL2 exists among native Batswana, and even though clinically indistinguishable from HD, molecular testing can result in positive case identification.

Preliminary report of HLA (DNA) typing of Nigerians using sequence-specific primer technique.

AIMS AND OBJECTIVES: This communication is an attempt to present the experience and a preliminary report of results over a one-year period. PATIENTS AND METHODS: From December 2011 to December 2012, a prospective determination of the HLA types of 20 individuals referred to the Tissue Typing Laboratory of the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife was done. These consisted of prospective transplant recipients, their donors, and a migrant pair for kinship determination. DNA was extracted from the client's peripheral blood sample, using the QIAmp Blood DNA Mini kit, (Qiagen). PCR was done using OlerupR low-resolution PCR-SSP typing kit. The PCR product was resolved in 2% agarose gel, and the bands visualised under UV light. The HLA types were determined using provided tables and/or Helmberg software. Data were presented using descriptive statistics whileHLA antigen frequency (AF) was expressed in percentage and gene frequency (GF) was determined using square root method (1-(1-AF)1/2). RESULTS: A total of 20 individuals (13males and 7females) consisting of seven renal transplant recipients and seven prospective donors; a stem cell recipient and three donors and a migrant pair for kinship determination were typed. Age ranged from 4-65 years. 44 HLA alleles were detected, while HLA-A, B, C, DRB1 and DQB1 were 7, 10, 11, 8, 8 alleles respectively. The alleles were heterogeneous in distribution while 6 antigens (HLA-A*02, B*30, C*15, DRB1*03, DRB1*08 and DQB1*06) were having frequencies e"25%. CONCLUSION: This report confirms that DNA-based HLA typing is feasible locally, andit was observed that renal transplantation procedure is the most frequent indication. The HLA antigens observed to have very high frequencies (e"25% frequency) in this population were HLA-A*02, B*30, C*15, DRB1*03, DRB1*08 and DQB1*06. There is a strong need to develop a broad-based HLA data bank for Nigeria to further strengthening her transplantation programmes.

Imatinib (Glivec) and gastrointestinal stromal tumours in Nigerians.

BACKGROUND: To assess the response and the impact on the overall survival (OS) on c-KIT-positive (CD117+) gastrointestinal stromal tumours (GISTs) patients treated with imatinib mesylate. METHODS: Between July 2003 and December 2012, consenting patients with advanced c-kit-positive GISTs were enrolled to receive imatinib mesylate therapy at a dose of 400mg - 800mg daily, supplied gratis by Novartis Pharma (Basel, Switzerland) under its GIPAP initiative. Disease severity was based on tumour site, size and mitotic index at diagnosis. Clinical features together with drug toxicity, haematological and biochemical parameters were monitored. Overall survival (OS) reviewed at 12 months intervals over 5 years was computed using Kaplan-Meier RESULTS: There were 27 patients in all (17 males and 10 females with a median age of 52 years (range 26 - 83). Twenty three patients, 15 males and 8 females that have been followed up for at least 6 months were evaluated, aged 26-83 years (median = 56). There were 17 (73.9%) gastric tumours and 6 extragastric including 3 cases of peritoneum and 1 each of small gut, colon and rectum. At diagnosis, 21 (91.3%) cases were high risk, and 1 each fell into the intermediate and low risks, respectively. Ten patients (43.4%) including 5 with metastases presented with unresectable lesions. Five patients (21.7%) had complete tumour resection, 5 (3 with metastases) had partial resections and 3 others with non-bulky, nonmetastatic diseases underwent no surgery. Imatinib was used as the primary therapy for all patients, except the 5 patients that underwent complete tumour resection. Nine (39.1%) patients were lost to disease progression with a median survival of 16.7 +/- 10.7 (+/- SE) (95% CI = 0-37.6) months. The overall survival at 2 years for all patients was 71.9%, which dropped to 65.9% at 4 years. CONCLUSIONS: Although a small number of GISTs, imatinib induced an extended remission in patients with advanced disease, most of whom would have been dead within a few months of diagnosis.

AIDS-related lymphomas in Nigeria

Aggressive non-Hodgkin's lymphoma (NHL), including primary central nervous system (CNS) lymphoma, lymphoblastic lymphoma and non-endemic Burkitt's lymphoma have been recognized as AIDS-defining cancers in most developed countries. However, HIV/AIDS epidemics appear not to have been associated with higher incidence of lymphomas in Africa. We therefore carried out this study to highlight the significance or otherwise of HIV/AIDS epidemics in the pathogenesis of lymphomas in a population of Nigerians with the disease. Since January 1993 to the present, all patients with haematologic cancers are routinely screened (following appropriate counseling) for HIV infection. Patients with a histological diagnosis of malignant chronic lymphoproliferative diseases {non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Burkitt's lymphoma (BL) and Hodgkin lymphoma (HL)} at the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife from January 1993 to August 2008 were noted. Those patients confirmed to be HIV/AIDS positive among the cohort with lymphomas were retrospectively studied using their clinical case notes. Data obtained were analyzed using appropriate descriptive and inferential statistics. A total of 391 patients were histologically confirmed to have lymphoma {NHL-109, (27.9 percent); CLL-76, (19.4 percent); BL-178, (45.5 percent) and HL-28, (7.2 percent)} during the study period. Nine patients (2.3 percent) were confirmed to be HIV- positive, all within the age bracket 24-60 (median = 50) years. Six of these, five males and one female, ages 24-60 (median = 37.5) years, had NHL while another three, all females (age 50 - 68years; median = 56 years) had CLL. None of the patients with HL and BL were HIV positive. Patients with NHL presented at advanced stage of the disease (at least clinical stage IIIb), and all those with CLL presented at stage C of the International Working Party Classification. All the HIV-positive patients ...

AIDS-related lymphomas in Nigeria.

Aggressive non-Hodgkin's lymphoma (NHL), including primary central nervous system (CNS) lymphoma, lymphoblastic lymphoma and non-endemic Burkitt's lymphoma have been recognized as AIDS-defining cancers in most developed countries. However, HIV/AIDS epidemics appear not to have been associated with higher incidence of lymphomas in Africa. We therefore carried out this study to highlight the significance or otherwise of HIV/AIDS epidemics in the pathogenesis of lymphomas in a population of Nigerians with the disease. Since January 1993 to the present, all patients with haematologic cancers are routinely screened (following appropriate counseling) for HIV infection. Patients with a histological diagnosis of malignant chronic lymphoproliferative diseases {non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Burkitt's lymphoma (BL) and Hodgkin lymphoma (HL)} at the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife from January 1993 to August 2008 were noted. Those patients confirmed to be HIV/AIDS positive among the cohort with lymphomas were retrospectively studied using their clinical case notes. Data obtained were analyzed using appropriate descriptive and inferential statistics. A total of 391 patients were histologically confirmed to have lymphoma {NHL-109, (27.9%); CLL-76, (19.4%); BL-178, (45.5%) and HL-28, (7.2%)} during the study period. Nine patients (2.3%) were confirmed to be HIV- positive, all within the age bracket 24-60 (median = 50) years. Six of these, five males and one female, ages 24-60 (median = 37.5) years, had NHL while another three, all females (age 50 - 68 years; median = 56 years) had CLL. None of the patients with HL and BL were HIV positive. Patients with NHL presented at advanced stage of the disease (at least clinical stage IIIb), and all those with CLL presented at stage C of the International Working Party Classification. All the HIV-positive patients with NHL succumbed to the disease within one to three weeks of admission into the hospital. The prevalence of AIDS-related lymphomas is 2.3% compared to 4.4% found in the general population. However, it is interesting that no single case of AIDS-associated BL was seen, despite the fact that Burkitt's lymphoma is endemic in this part of the world. All the patients presented at a very advanced stage of the disease with significantly shortened survival.

Herpes zoster complicating imatinib mesylate for gastrointestinal stromal tumour.

Varicella zoster virus (VZV) infection is uncommon in patients with gastrointestinal stromal tumour (GIST) and who have not been exposed to extensive radiotherapy and/or high-dose chemotherapy. We report a 56-year-old Nigerian man with GIST who developed VZV infection while on imatinib mesylate therapy. From August 2003 to November 2005, 64 patients (GIST/CML = 6/58) were enrolled into an ongoing Glivec (imatinib mesylate) international patient-assistance programme therapy for Philadelphia/bcr-abl-positive chronic myeloid leukaemia (CML) and CD117-positive GIST patients at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. The patient developed herpes zoster (HZ) infection 23 months into therapy with Glivec. With his absolute lymphocyte count at 2,774 cells per microlitre and CD4 count at 950 cells per microlitre, no obvious immunological defect was observed. Prompt resolution of symptoms without sequelae was achieved by treating with acyclovir, analgesic and dressing of lesions with desiccant. To our knowledge, this is the first reported case of HZ infection in a patient with GIST on Glivec therapy, and the response is similar to that of CML patients who developed VZV while on similar therapy.

Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up.

We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)/acute lymphoblastic leukemia=25/19) who underwent allogeneic transplantation at our center between 11/1990 and 04/2004. The median leukemic blasts was 25% and age 28 years (range, 3-56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body irradiation and etoposide (Bu/Cy/VP, n=22; TBI/Cy/VP, n=17; others, n=5) followed by marrow or peripheral blood transplant (n=23/21) from unrelated or related donors (n=28/16). All patients had graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. One patient experienced late graft failure. Severe acute-GVHD and chronic-GVHD appeared in eight and 14 patients, respectively. Thirteen patients (30%) remain alive after a median of 25.3 months (range, 2.4-134.1); with 31 deaths, mostly from relapse (n=15) and infections (n=12). Overall survival (OS) and progression-free survival (PFS) at 5 years was 28 and 26%, respectively. OS and PFS were significantly better with blasts < or =20% and time to transplant < or =1 year while transplant-related mortality was less with the use of TBI. We conclude that patients with refractory leukemia can benefit from allogeneic BMT, especially with < or =20% marrow blast.

Haematological parameters in prospective nigerian blood donors rejected on account of anaemia and/or microfilaria infestation.

BACKGROUND: Worldwide, prospective blood donors are screened for blood transfusion-transmissible diseases. In addition, predonation fitness requires adequate haematocrit and, in the tropics, negative screening for microfilaria that may precipitate allergy. The high prevalence of anaemia and microfilaria, though treatable, has contributed to the dearth of eligible blood donors. This study aims to characterize anaemia in prospective blood donors rejected for anaemia and find haematological effects of microfilarial infestation in prospective blood donors. METHODS: This prospective study was carried out from 1st of August to November 30th, 2002 at the blood transfusion unit of the Haematology Department of Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife. All consenting prospective blood donors that were rejected for anaemia and or microfilaria infestation during the study period were studied for their age, sex and haematological profile. A randomly selected population of successful donors was similarly studied. RESULTS: Sixty rejected prospective blood donors (5.2% of the total screened)) were studied. Forty-five (75%) of them were rejected for anaemia alone, 10 (16.7%) for microfilaria alone and 5 (8.3%) for both anaemia and microfilaria. The mean ages of those rejected were 33.3(+/- 9.9) years for anaemia alone, 29.9(+/- 8.5) years for microfilaria alone and 35.4(+/- 8.3) years for those with anaemia and microfilaria combined. The mean age of the successful group was 28.9(+/- 8.5) years. Of the 60 rejected subjects, 53 were males while 7 were females. Blood film of the anaemia group revealed features suggestive of iron deficiency anaemia (hypochromic microcytic cells) in 60% of them. The white cell count (WCC) was significantly increased in the microfilarial group compared to others and it revealed lymphocytosis and eosinophilia. CONCLUSION: The importance of these findings have been discussed in line with the existing literature. The need for intensive health education to encourage voluntary donation and promote the interest of females in blood donation is emphasized.