Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in the AK1 gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in the AK1 gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger’s sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation in AK1 gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population.

Objective. The aim of this paper is to report the case of Wiskott-Aldrich syndrome (WAS) that presented with unusual laboratory features. Clinical Presentation and Intervention. Male neonate admitted with symptoms related to thrombocytopenia, whose initial diagnosis was considered as neonatal alloimmune thrombocytopenia and JMML (juvenile myelomonocytic leukemia) but subsequently diagnosis was confirmed as WAS. Conclusion. This case shows that a suspicion of WAS is warranted in the setting of neonatal thrombocytopenia with JMML-like blood picture and normal sized platelets.

No abstract

No abstract

Background: Vitamin D deficiency has been recently associated, as an independent risk factor, with lower rates of progression-free survival (PFS) and overall survival (OS) in patients with Hodgkin (HL) and non-Hodgkin's lymphoma (NHL). Aims: To investigated the impact of vitamin D status on the outcome of lymphoma patients in two Institutions. Methods: From 2015 to 2018, we tested circulating 25-hydroxyvitamin D3 (25[OH]D3) levels in a prospective cohort of 135 newly diagnosed patients with NHL and HL in two Institutions in Spain. 25[OH]D3 levels were measured by chemoluminescent immunoassay. Determinations were based on guidelines from the Food and Nutrition Board of the Institute of Medicine. According to current guidelines, we considered the following thresholds: vitamin D deficient (<10 ng/ml), vitamin D insufficiency (10 to 30 ng/ml) and normal vitamin D level (>30 ng/ ml). Patients with <20 ng/ml from one Institution had vitamin D substitution. OS and PFS were calculated using Kaplan-Meier estimators, comparison between categories performed by log-rank test and Cox PH regression, and the effect of covariates reported with 95% confidence interval (95 CI). Results: 135 newly diagnosed patients with NHL and HL were included. Median age at diagnosis was 67 years (range, 20 to 91 years). NHL subtypes: 47% diffuse large b cell lymphoma (DBCL), 30% Indolent lymphoma, 5% mantle cell lymphoma, 6% Tcell lymphoma, 10% Hodgkin lymphoma and 3% others NHL 34% had advanced stage and and 39% of NHL patient had ≥ 3score of International Pronostic Index (IPI).55% of the patients were diagnosed in spring or summer. Median 25(OH)D levels at diagnosis were 18 ng/ml. 11% of patients had normal 25(OH)D levels, 77% had insufficient 25(OH)D levels and 12% were deficient at lymphoma diagnosis. Median follow-up was 12 months and 22 deaths were observed. The three groups of vitamin D levels were associated with OS, but this difference was not statistically significant (Figure 1). In the DLBCL subset, we inspected in a Cox Model the effect of Vitamin D levels for OS/PFS, adjusting for IPI Score and vitamin D substitution. Vitamin D levels did not achieve statistical significance for PFS (hazard ratio [HR], 1.02; 95% CI, 0.99 to 1.04) and OS (HR: 0.99; 95% CI, 0.94 to 1.06). Remarkably, there was a tendency towards a better statistically significant outcome in patients supplemented (HR for PFS: 0.36; 95% CI, 0.10 to 1.29; p = 0.10). Summary/Conclusion: Most of our patients present with low levels of vitamin D[JPD1] . In our limited series, with the current follow-up time, baseline vitamin D values did not significantly impact PFS and OS. Further studies are needed to confirm our data.