A Novel mtDNA Large-Scale Mutation Clinically Exclusively Presenting With Refractory Anemia

Abstract

We report a rare case of juvenile cobalamin deficiency who presented at the age of seventeen years. He was underweight and had skin changes, normocytic anemia and autonomic dysfunction which lead to adynamic ileus and acute post-renal failure. The expected macrocytosis was masked by an underlying alpha thalassemia trait. The patient had an excellent response to parenteral cobalamin treatment.

Haematological abnormalities in mitochondrial disorders

“…This finding is consistent with other reports, where anaemia was also more frequent in MIDs than abnormalities in thrombocyte or leucocyte count (either as the sole, dominant or collateral feature of the phenotype) (Table VIII). (17,21) Although anaemia as a sole manifestation of MID was not seen in the present study, it has been previously reported in a patient carrying a large-scale mtDNA deletion (encompassing the genes ATPase6, COX-III, ND3, ND4, ND5, ND6 and cytb). (21) In another case, a mutation in the nDNA-located gene, SLC25A38, which encodes a carrier of the inner mitochondrial membrane, resulted in isolated non-syndromic microcytic, hypochromic and sideroblastic anaemia (autosomal recessive pyridoxinerefractory sideroblastic anaemia).…”

“…(17,21) Although anaemia as a sole manifestation of MID was not seen in the present study, it has been previously reported in a patient carrying a large-scale mtDNA deletion (encompassing the genes ATPase6, COX-III, ND3, ND4, ND5, ND6 and cytb). (21) In another case, a mutation in the nDNA-located gene, SLC25A38, which encodes a carrier of the inner mitochondrial membrane, resulted in isolated non-syndromic microcytic, hypochromic and sideroblastic anaemia (autosomal recessive pyridoxinerefractory sideroblastic anaemia). (17) Anaemia as the sole feature of the phenotype is also characteristic of XLSA.…”

“…MIMODS). (21) Sideroblastic anaemia is heterogeneous and characterised by excess iron accumulation in the mitochondria of erythroblasts. (11,26) The morphological hallmark of sideroblastic anaemia is the ring sideroblast, a pathological erythroid precursor containing an excessive amount of non-heme iron deposits in the mitochondria with perinuclear distribution, generating a ring appearance.…”

Novel 5.712 kb mitochondrial DNA deletion in a patient with Pearson syndrome: A case report

“…No strict correlations have been observed between heteroplasmy in blood cells and the severity of hematopoietic features. Furthermore, no obvious genotype-phenotype correlation has been identified regarding the appearance of hematological manifestations in PS and the mtDNA deletion (18). The different phenotypic expression of the same mtDNA defects may be associated with nuclear modifier genes, polymorphisms and environmental factors (19).…”

Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation

“…The majority of CPEO patients present homoplasmic large-scale deletions in mitochondrial DNA (mtDNA) [4]. Mitochondrial disease-associated FSGS has mainly been reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) [5], another type of mitochondrial disease caused by heteroplasmic point mutations in mtDNA, mainly m.3243A>G transitions.…”