Hb Lepore/β0-Thalassaemia With α+-Thalassaemia Interactions, A Potential Diagnostic Pitfall

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

The Prevalence of Sensorineural Hearing Loss in β-thalassaemia patient treated with Desferrioxamine

Objective: This study aimed to evaluate the prevalence of sensorineural hearing loss (SNHL) in β-thalassaemia patients treated with Desferrioxamine (DFO) and determine the correlation of SNHL with average daily DFO dosage, serum ferritin level and Therapeutic index (T.I). Methods: This is a cross sectional descriptive study carried out for a period of 14 months and 54 patients were recruited. The recruited patients are transfusion dependant β- thalassaemia patient aged 3 years and above treated with DFO. An interview, clinical examination and hearing assessment, which included tympanogram, and Pure Tone Audiometry (PTA) or behaviour alaudiometry were performed. The data on age started on DFO, average daily DFO, duration of DFO intake, serum ferritin past 1 year and Therapeutic Index (T.I) were obtained from patients’ case notes. Results: The prevalence of SNHL was 57.4% and majority has mild hearing loss (93.6%). Fourteen patients (25.9%) have bilateral ear involvement and as many as 17 patients (31.5%) have SNHL in either ear. A total of 23 patients (42.6%) have normal hearing level. Although the prevalence of SNHL was 57.4%, only a small percentage of the patient noticed and complained of hearing loss (11.1%). There is no association between age started on DFO, average daily DFO and duration of DFO intake with normal hearing group and those patients with SNHL. Positive correlation was seen between average daily DFO with 2000 and 4000Hz on PTA in the left ear and between serum ferritin level past 1 year with 4000 and 8000Hz in the right ear and 8000Hz in the left ear. No significant correlation was seen between T.I on PTA. Conclusion: The prevalence of SNHL from hearing assessment is high in β-thalassaemia patients in this study. However, it is manifested clinically in a smaller percentage. We suggest a baseline hearing assessment should be carried on all β-thalassaemia patients prior to DFO chelation therapy.

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer.

BACKGROUND: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. METHODS: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). RESULTS: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. CONCLUSION: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.