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Hemolytic anemia with null PKLR mutations identified using whole exome sequencing and cured by hematopoietic stem cell transplantation combined with splenectomy

Bone Marrow Transplantation volume 51, pages 1605–1608 (2016)Cite this article

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Genetic testing has become clinically available and is now used for the confirmatory diagnosis of Mendelian disorders. However, when confirmatory genetic testing for an initial diagnosis is negative, the potential disease is diversified into various disorders showing similar clinical and laboratory features. In that situation, time and effort are required to make an accurate diagnosis. High-throughput sequencing, previously performed on a research basis, is very useful to genetically differentiate clinically similar diseases.1, 2

In this study, we present two sibling patients who initially exhibited congenital dyserythropoietic anemia (CDA)-associated features but were finally identified as having two PKLR null mutations using whole exome sequencing (WES). The patients were a Korean boy and his younger sister. The boy presented with neonatal anemia, a complete blood count (CBC) with a leukocyte count of 7.7 × 109/L, hemoglobin (Hb) of 7.9 g/dL and platelet count of 470 × 109/L. The RBC indices included a mean corpuscular volume (MCV) of 88.6 fL, a mean corpuscular Hb (MCH) of 30.1 pg and a MCH concentration (MCHC) of 34.0%. The values of the indices were characteristic of normocytic normochromic anemia. The total and indirect bilirubin levels were 2.92 and 2.61 mg/dL, respectively. The lactate dehydrogenase (LD) level was 1166 IU/L (reference range 250–450 IU/L), and the haptoglobin level was lower than the detection limit (reference range 30–200 mg/dL). A peripheral blood (PB) smear revealed anisocytosis, and a paroxysmal nocturnal hemoglobinuria investigation by flow cytometry was normal. The bone marrow (BM) revealed CDA-associated features and a normal karyotype. The patient was examined regularly and received blood transfusions and an iron chelating agent, deferasirox. A sister was born when the male patient was 3 years and 10 months old. She also developed neonatal anemia and required blood transfusions. When she was 7 months old, she was admitted for evaluation of a possible hematologic disorder similar to her brother's. She exhibited a leukocyte count of 3.3 × 109/L, Hb of 10.8 g/dL and platelet count of 202 × 109/L. Her RBC indices were as follows: MCV 86.4 fL, MCH 29.1 pg and MCHC 33.6%, indicating normocytic normochromic anemia. Her total and indirect bilirubin levels were 2.69 and 2.22 mg/dL, respectively. Her LD level was 894 IU/L, and haptoglobin was not detected. A PB smear revealed normal morphology, and the BM revealed 100% cellularity and marked erythrocytosis with dysplasia, similar to her brother. She attended regular follow-up visits with regular blood transfusions.

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Acknowledgements

We are grateful to the patients and their parents, and The Catholic Genetic Laboratory Center for assisting us in carrying out this study and compiling this report. This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120175 and HI14C3417).

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  1. Y Kim and N-G Chung: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    M Kim, J Park, J Lee, W Jang, H Chae & Y Kim

  2. Catholic Genetic Laboratory Center, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    M Kim, J Park, J Lee, W Jang, H Chae, H Choi, J Kim, A Kwon & Y Kim

  3. Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    J-W Lee, B Cho & N-G Chung

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Kim, M., Park, J., Lee, J. et al. Hemolytic anemia with null PKLR mutations identified using whole exome sequencing and cured by hematopoietic stem cell transplantation combined with splenectomy. Bone Marrow Transplant 51, 1605–1608 (2016). https://doi.org/10.1038/bmt.2016.218

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