Congenital amegakaryocytic thrombocytopenia with severe neurological findings O ¨ zcan Bo ¨r a , Ayse B. Turhan a and Coskun Yarar b Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive disorder characterized by thrombocytopenia from failure of megakaryopoiesis. The genetic background of CAMT is mutations in the myeloproliferative ligand gene encoding the thrombopoietin receptor. In our patient with CAMT, we identified homozygous missense mutations [c.407C>T (p.P136L)]. The association of CAMT and central nervous system (CNS) abnormalities is uncommon. Here we present a case in which CAMT appears linked to CNS abnormalities (encephalomalacia, global atrophy) and developmental delay related with intrauterine intracranial hemorrhage. Blood Coagul Fibrinolysis 26:000–000 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. Blood Coagulation and Fibrinolysis 2016, 27:00–00 Keywords: amegakaryocyte, central nervous system abnormalities, mutation, newborn, thrombocytopenia a Division of Pediatric Hematology and Oncology and b Division of Pediatric Neurology, Department of Pediatrics, University of Eskis ¸ehir Osmangazi, School of Medicine, Eskisehir, Turkey Correspondence to Ayse B. Turhan, Division of Pediatric Hematology and Oncology, Department of Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir 26480, Turkey. Tel: +0090 530 527 19 þ97; fax: +0090 216 651 98 58; e-mail: aysebturhan@hotmail.com Received 2 July 2015 Revised 4 November 2015 Accepted 7 November 2015 Introduction Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder characterized by thrombocytopenia and absence or decline in the number of megakaryocytic precursors in the bone marrow. In most of the cases the disease is caused by homozygous or compound heterozygous mutations in the gene myeloproliferative ligand (MPL) encoding the receptor for the hematopoie- tic growth factor thrombopoietin [1–3]. The association of CAMT and central nervous system (CNS) abnormalities is uncommon. c-Mpl is expressed not only in platelets, but also in hematopoietic precursor cells, brain and liver among other organs. c-Mpl mutation may also affect brain development during infancy, explaining the association between thrombocytopenia and cerebral malformations in some patients with CAMT [4,5]. The most frequently described CNS malformations in patients with CAMT are intra or extra utero intracra- nial hemorrhages reported in only up to 25% of patients [4]. The association between CAMT and other types of CNS malformations is even less common. Here we present a case where CAMT appears linked to CNS abnormalities (encephalomalacia, global atrophy) and developmental delay. Brief report Our patient was referred to our hospital with the com- plaint of petechiae and thrombocytopenia (12 000/mm 3 ) at the 7th day of life. Physical examination, hemoglobin and white blood cell count and mean corpuscular eryth- rocyte volume were normal. When viewed on peripheral blood smears, platelets were of normal size and granu- larity. Over the first 3 days the blood culture was sterile and antibiotic treatment was stopped. A urine culture for cytomegalovirus was negative, as were rapid diagnos- tic tests for herpes simplex and titers for toxoplasmosis, cytomegalovirus, rubella and herpes. An echocardiogram was normal, as was a head ultrasound study. Almost daily platelet transfusions were required to maintain platelet counts higher than 50 000/mm 3 in the neonatal period. Bone marrow aspirate has been performed at the 19th day of life, and revealed as apparently normocellular bone marrow morphology with decreased number of megakary- ocytes with normal nuclear lobulation and cytoplasmic granularity. The full spectrum of erythroid and myeloid maturation was present with no dyspoietic features in addition to no evidence of malignancy, leukemia, lymphoma and metastasis. In neonatal period, cranial magnetic reson- ance imaging revealed chronic bleeding areas (Fig. 1). There were no responses to either recurrent intravenous immunoglobulin or steroid treatment. Beyond 8 month of age, platelet counts were maintained higher than 10 000–20 000/mm 3 with transfusions twice a week. Genetic analysis revealed as CAMT, with positive homozygous mutation of c-Mpl [c.407C>T (p.P136L)]. During the follow-up period, progressive and severe neurodevelopmental delay has been seen. On physical examination, he had increased muscle tone, especially in the lower extremities, and flexion deformities have been noted on the right hand. Cranial magnetic resonance imaging revealed encephalomalacia and global atrophy (Fig. 2). Neurological findings of our patients with spastic hemiplegic cerebral palsy were called. Neurological course and findings of our patient might be related with Case report 1 0957-5235 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/MBC.0000000000000508 Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.