The neurologic aspects of transcobalamin II deficiency

Hall, Charles A.

doi:10.1111/j.1365-2141.1992.tb06410.x

Cited by 50 publications

(17 citation statements)

References 16 publications

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“…The serum cobalamin levels must be kept very high to treat TC-deficient patients successfully (Rosenblatt and Whitehead 1999). Neurological symptoms are rare in TC deficiency; they most often occur as a result of delayed or improper treatment (Hall 1992). TCdeficient patients need also to be monitored for retinopathy (Dharmasena et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Prasad

Rosenblatt

Corley

et al. 2008

J of Inher Metab Disea

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It is unusual for inborn errors of metabolism to be considered in the investigative work-up of pancytopenia. We report a family in which the proband presented with failure to thrive at 2 months of age and subsequent bone marrow failure. A previous sibling had died at 7 months of age with suspected leukaemia. Haematological findings in the proband were significant for pancytopenia, and bone marrow aspiration showed dysplastic changes in all cell lineages. Urinary organic acid analysis revealed elevated methylmalonic acid. The synthesis of transcobalamin II (transcobalamin, TC) by cultured fibroblasts was markedly reduced, confirming the diagnosis of TC deficiency. The proband and his younger asymptomatic sister (also found to have TC deficiency) were homozygous for R399X (c.1195C>T), a novel mutation resulting in the loss of the C- terminal 29 amino acids of TC, a highly conserved region. Response to parenteral vitamin B(12) in the proband was dramatic. At 6 years 3 months of age, physical examination is normal and developmental level is age appropriate. His sister is clinically asymptomatic and is also developing normally. Propionylcarnitine concentrations were not elevated in the newborn screening cards from the proband and sister, but that was for specimens retrieved from storage after 7 years and 5 years, respectively. Inherited and acquired cobalamin disorders should both be considered in the differential diagnosis of bone marrow failure syndromes in young children. Early detection of the metabolic causes of bone marrow failure can ensure prompt recovery in some cases involving the vitamin B(12) pathway.

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Section: Discussionmentioning

confidence: 99%

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Prasad

Rosenblatt

Corley

et al. 2008

J of Inher Metab Disea

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“…11 Transcobalamin II deficiency is a autosomal recessive disorder that leads to absence of transcoba lamin II and symptoms of vitamin B12 deficiency. 12,13 Transcobalamin II (TCII) is a carrier protein for vitamin B12 in the plasma and is responsible for delivery of the vitamin to the cell via the TCII receptor. 14 The TCII gene is located on chromosome 22q12 -13.…”

Section: Discussionmentioning

confidence: 99%

Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation

et al. 2008

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We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues. His parents were found to be carriers of a nonsense mutation of the PMS2 gene.

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“…This retinal degeneration resembles the ophthalmologic complications reported in some patients with inherited intracellular Cbl type C defect (Gerth et al 2008). An additional TC-deficient patient has been described with retinal degeneration (Dharmasena et al 2008), which, along with neurological impairment, is possibly attributable to insufficient and/or orally administered Cbl therapy, with subsequent severe intracellular Cbl depletion and defective CNS remethylation (Hall 1992;Surtees 1998).…”

Section: Discussionmentioning

confidence: 98%

Should transcobalamin deficiency be treated aggressively?

Schiff

Baulny²,

Bard³

et al. 2010

J of Inher Metab Disea

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Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.

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The neurologic aspects of transcobalamin II deficiency

Cited by 50 publications

References 16 publications

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation

Should transcobalamin deficiency be treated aggressively?

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