Report of rapid diagnosis and precise management of MMADHC-related intracellular cobalamin defect

Disorders of intracellular cobalamin metabolism are a group of metabolic disorders that lead to varied clinical presentation from intrauterine life to adulthood. We report a male infant with developmental regression, macrocytic anaemia and hyperpigmentation. Exome sequencing identified a homozygous pathogenic variant in the MMADHC gene, known to cause homocystinuria, cblD type (MIM #277410). We describe significant clinical improvement with targeted therapy and emphasise the relevance of genomic testing in accurate management of inherited metabolic disorders.

The VEXAS Syndrome: Uncontrolled Inflammation and Macrocytic Anaemia in a 77-Year-Old Male Patient

The VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described X-linked autoinflammatory condition caused by a somatic mutation of the UBA1 gene and characterized by an evolving phenotype. This includes inflammatory processes such as recurrent fever, Sweet’s syndrome of the skin, pulmonary fibrosis, relapsing polychondritis and venous thromboembolism. An important feature, present in almost all cases, is the development of a macrocytic anaemia with vacuolization of myeloid and erythroid precursors. Usually, these patients require high doses of steroids to control symptoms and respond poorly to disease-modifying drugs. We describe a new case of the VEXAS syndrome presenting with Sweet’s syndrome which has now been followed for 6 years.

Hyperregenerative macrocytic anaemia: the role of copper and zinc

In a patient with a history of bariatric surgery, severe copper deficiency presenting with macrocytic hyperregenerative anaemia was diagnosed. Besides the impaired intestinal absorption due to a short bowel syndrome, the enteral zinc supplementation competitively decreased the intestinal copper uptake. Once the zinc supplementation was stopped, enteral copper replacement ensued and normalised haemoglobin levels with decreasing median corpuscular volume were observed during follow-up visits.

A complex comprising C15ORF41 and Codanin-1: the products of two genes mutated in congenital dyserythropoietic anaemia type I (CDA-I)

Congenital dyserythropoietic anaemia (CDA) type I is a rare blood disorder characterised by moderate to severe macrocytic anaemia and hepatomegaly, with spongy heterochromatin and inter-nuclear bridges seen in bone marrow erythroblasts. The vast majority of cases of CDA type I are caused by mutations in the CDAN1 gene. The product of CDAN1 is Codanin-1, which interacts the histone chaperone ASF1 in the cytoplasm. Codanin-1 is a negative regulator of chromatin replication, sequestering ASF1 in the cytoplasm, restraining histone deposition and thereby limiting DNA replication. The remainder of CDA-I cases are caused by mutations in the C15ORF41 gene, but very little is known about the product of this gene. Here, we report that C15ORF41 forms a tight, near-stoichiometric complex with Codanin1 in human cells, interacting with the C-terminal region of Codanin-1. We present the characterisation of the C15ORF41–Codanin-1 complex in humans in cells and in vitro, and demonstrate that Codanin-1 appears to sequester C15ORF41 in the cytoplasm as previously shown for ASF1. The findings in this study have major implications for understanding the functions of C15ORF41 and Codanin-1, and the aetiology of CDA-I.

Pernicious Anaemia with Normal Vitamin B12

A 49-year-old female patient presented to our hospital with asthenia, odynophagia, low grade fever, worsening symptoms of chronic depression, and symmetric leg paresthesias. Investigations showed macrocytic anaemia, leucopenia, thrombocytopenia, high lactate dehydrogenase levels and a normal Coombs test. Trilineage dysplasia was detected in the bone marrow biopsy specimen. The diagnostic work-up led us to the diagnosis of pernicious anaemia with a spuriously normal value of vitamin B12 and high titres of anti-intrinsic factor autoantibodies. This case highlights the importance of considering vitamin B12 deficiency in the differential diagnosis of myelodysplasia, even when vitamin B12 levels seem to be normal.

Study of Anaemia in Children with Severe Acute Malnutrition

Introduction: Severe anaemia is a leading cause of paediatric morbidity, hospitalization, and mortality and it is very important co morbidity in children with severe acute malnutrition. Severe Acute Malnutrition (SAM) with anaemia has been shown to have 2.62 times higher mortality as compared to SAM with no anaemia. So this study was done to evaluate this co-morbidity further. The aim of present study was to determine the prevalence and type of anaemia and to evaluate the possible aetiologies of anaemia in severe acute malnourished (SAM) children.Material and Methods: In tertiary care hospital a cross sectional study was conducted over a period of 8 month with 100 cases of SAM children and 101 cases of normal children. In both cases disorders of primary haematological problem were excluded. Auto analysers were used to measure blood counts. Blood smear was analysed by pathology consultant of institute and recorded for all patients with anaemia. Grade of anaemia and morphologic type of anaemia was analysed. Data were entered in Excel spreadsheets and analysed using SPSS 20.0.Results: Patient with SAM 42% had moderate anaemia and 19% had severe anaemia in contrast 41.6% and 16.8% in NON SAM child respectively. Predominant morphologic type in SAM patient was macrocytic anaemia (33%), while in controls microcytic anaemia (40.6%) was more prevalent.Conclusion: There was a high prevalence of anaemia in SAM children. Major morphologic type in SAM children was macrocytic anaemia which may indirectly show vitamin B12 or folic acid deficiency in these children.