Page 258 - 2021_06-Haematologica-web

Letters to the Editor
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Figure 1. Family pedigree charts of five homozygous Southeast Asian ovalocytosis cases. Families of each homozygous Southeast Asian ovalocytosis (SAO) cases are represented: (A) GO 003/10, (B) GO 001/14, (C) GO 010/10, (D) GO 012/19, and (E) GO 012/13. Squares and circles denote male and females, respectively, with filled ones (grey or black) showing members affected with SAO. The numbered triangle (C) shows number of spontaneous abortions that occurred in the couple’s past pregnancies. Parents of two SAO homozygous children (GO 012/19 and GO 010/10) had multiple unsuccessful pregnancies. The mother of GO 012/19 suffered two intra-uterine deaths (including GO 012/19), while the mother of GO 010/10 suffered three spontaneous abortions. None of these other unsuccessful pregnancies were investigated further. On the other hand, parents of GO 012/13 have two living children among whom one is SAO het- erozygous, while parents of GO 012/19 have three living children with unknown SAO status (see the Online Supplementary Table S2). d: died; IUD: intra-uterine death.
revealed pale appearance, distended abdomen due to hepatosplenomegaly, and jaundice in all five cases. One of the five cases was reported to have dRTA diagnosed in the third month14 but the other four were not tested. Despite medical interventions, all five homozygous SAO children failed to thrive. This could be due to hepatosplenomegaly, severe anemia or lack of appropri- ate clinical management. It is difficult to gain more insights into the implications of the SAO homozygous cases as incomplete clinical data of the SAO cohort was collected, lacking data on hemoglobin abnormalities and blood group compatibility. It is also not known whether prenatal diagnosis and termination of pregnancy were offered. These services are not always available, and/or not acceptable to parents. It is now evident that careful clinical management can improve the life of homozygous SAO individuals.4 The long-standing assumptions that homozygous SAO is lethal, and that heterozygous SAO is asymptomatic should be re-assessed.
Several point mutations in AE1 that result in a wide range of complications have been reported, many of them leading to anemia and dRTA.2,12 Hemolytic anemia is recorded in children with homozygous G701D or com- pound heterozygous G701D/SAO, V850/SAO, A858D/SAO and V850/A858D mutations.1 Therefore, homozygous SAO and other AE1 null individuals, who show disparity in survival, may be indicating the cumula- tive result of hemolysis, acidosis and other hematological abnormalities influenced by the co-occurrence of addi- tional mutations.
To our knowledge, this preliminary Malaysian SAO cohort study, for the first-time reports five homozygous
SAO live-born cases. Since Malaysia and Southeast Asia have a high prevalence of SAO it would be beneficial to screen for SAO at antenatal clinics, at least for parents with a history of hydropic or stillborn fetuses. It is also essential to investigate the impact of heterozygous mutant SAO AE1 on other pathological conditions and ageing. Development of international and national guide- lines for assessing a number of hematological, renal, and hepatic conditions in combination with genetic mutation markers to improve survival of homozygous AE1 null probands is needed.
Amanda A. Lavinya,1 Ruzzieatul A. Razali,2
Munirah A. Razak,3 Rashidah Mohamed,4
Emmanuel J. Moses,5 Meera Soundararajan,6 Lesley J. Bruce,7 Jeyanthy Eswaran1,8 and Narazah Mohd Yusoff5
1Newcastle University Medicine Malaysia, Johor, Malaysia; 2Clinical Genetics Section, Advanced Medical and Dental Institute (AMDI), University Sains Malaysia, Penang, Malaysia; 3Pathology Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 4Pathology Department, Hospital Ampang, Selangor, Malaysia; 5Cluster of Regenerative Medicine, Advanced Medical and Dental Institute (AMDI), University Sains Malaysia, Penang, Malaysia; 6Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, UK; 7Bristol Institute for Transfusion Sciences, NHS Blood and Transplant, Bristol, UK and 8Institute of Clinical and Translational Research, Faculty of Medicine, Newcastle University,
Newcastle upon Tyne, UK
Correspondence:
NARAZAH MOHD YUSOFF - narazah@usm.my
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haematologica | 2021; 106(6)