To the Editor, Cytidine triphosphate (CTP) synthase 1 is responsible for the catalytic conversion of uridine triphosphate to CTP in lymphocytes [1]. This reaction is important for the biosynthesis of nucleic acids, playing a key role in lymphocyte function and turnover [1, 2]. Lack of this enzyme due to mutation in CTPS gene is associated with impaired capacity of activated T and B lymphocytes to proliferate in response to antigen-induced activation. Patients with this mutation all have ancestors from the North West of England [1] and present in the first decade of life with severe acute and chronic herpes virus infections and recurrent infections with encapsulated bacteria. There is a high risk of Epstein Bar virus (EBV)-driven lymphoma [1]. This is a potentially lifethreatening primary immune deficiency (PID) and longterm survival has not been reported.

We report on 11 patients with CTPS1 mutations who underwent hematopoietic stem cell transplant (HSCT) at three UK centres (London, Manchester and Newcastle). The molecular diagnosis was made pre-HSCT in six patients and retrospectively in five patients who had undergone HSCT for previously undiagnosed life-threatening PID. All patients had the same homozygous NM_001905. 3: c. 1692-1 G> C mutation (rs145092287) mutation and all the parents were heterozygous carriers. This mutation is known to lead to an abnormal transcript lacking exon 18 and complete lack of protein expression [1]. Six patients had an affected sibling. Patient 1 had 2 affected siblings who died of infection and hemophagocytic lymphohistiocytosis (HLH) in early childhood and patient 2 also had a sibling who died of overwhelming varicella zoster virus (VZV) and EBV infections before diagnosis. Pre-transplant features are summarised in Table 1. Systemic viral infections were seen in all patients, with acute and chronic EBV infections in nine patients, four suffering from EBV-driven lymphoproliferative disease (LPD)(two CNS and one lung) and one with EBV-driven HLH. Four patients had severe chickenpox. Five patients presented with chronic diarrhoea. Four patients with EBV-driven LPD received rituximab and three EBV-specific cytotoxic T lymphocytes (CTLs)(two pre-transplant and one post transplant). The age of the patients at transplant ranged from 15 months to 17 years. The source of stem cells was peripheral blood in seven patients, bone marrow in three and cord blood in one. Eight received matched (10/10) donor stem cells, two had 1/10 mismatches and one received a haploidentical 6/10 transplant from his father as there were no suitable matched donor (Table 2). All but one received conditioning with fludarabine in combination with treosulfan (n= 3), melphalan (n= 4), treosulfan and thiotepa (n= 1, the nonreduced-intensity conditioning protocol) or low-dose busulfan (n= 2)[3], one received treosulfan and cyclophosphamide. All but one patient received serotherapy with