Should transcobalamin deficiency be treated aggressively?

Schiff, Manuel; Baulny, Hélène Ogier de; Bard, Ghislaine; Barlogis, Vincent; Hamel, Christian; Moat, Stuart; Odent, Sylvie; Shortland, Graham; Touati, Guy; Giraudier, Stéphane

doi:10.1007/s10545-010-9074-x

Cited by 33 publications

(32 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The anemia is usually megaloblastic and, in some cases, is seen in the context of pancytopenia or isolated erythroid hypoplasia. TC deficiency has been misdiagnosed as leukemia (Schiff et al 2010) as has B12/folate deficiency (Aitelli et al 2004). Delayed or inadequate treatment, as well as administration of folate in the absence of Cbl, can all lead to neurological deficits including developmental delay, neuropathy, myelopathy, and retinal degeneration (Hall 1992;Souied et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Trakadis

Alfares

Bodamer

et al. 2013

J of Inher Metab Disea

View full text Add to dashboard Cite

Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.

show abstract

Section: Introductionmentioning

confidence: 99%

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Trakadis

Alfares

Bodamer

et al. 2013

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Because only a minority of circulating cobalamin is bound to transcobalamin, serum cobalamin level is usually in the reference range or only slightly reduced. Patients may have immature white cell precursors in an otherwise hypocellular bone marrow, leading in some cases to misdiagnosis as leukemia [Meyers and Carmel, 1984; Schiff et al, 2010]. Most patients that have been investigated had absence of immunologically detectable transcobalamin, although patients with a physiologically inactive transcobalamin have been described [Haurani et al, 1979; Seligman et al, 1980; Cooper and Rosenblatt, 1987].…”

Section: Introductionmentioning

confidence: 99%

Inborn errors of cobalamin absorption and metabolism

Watkins

Rosenblatt²

2011

American J of Med Genetics Pt C

174

View full text Add to dashboard Cite

Derivatives of cobalamin (vitamin B(12)) are required for activity of two enzymes in humans. Adenosylcobalamin is required for activity of mitochondrial methylmalonylCoA mutase and methylcobalamin is required for activity of cytoplasmic methionine synthase. Deficiency in cobalamin, or inability to absorb cobalamin normally, can result in accumulation of methylmalonic acid and homocysteine in blood and urine. Methylmalonic acidemia can result in metabolic acidosis which in severe cases may be fatal. Hyperhomocysteinemia along with hypomethioninemia can result in hematologic (megaloblastic anemia, neutropenia, thrombocytopenia) and neurologic (subacute combined degeneration of the cord, dementia, psychosis) defects. Inborn errors affecting cobalamin absorption (inherited intrinsic factor deficiency, Imerslund–Gra¨ sbeck syndrome) and transport (transcobalamin deficiency) have been described. A series of inborn errors of intracellular cobalamin metabolism, designated cblA-cblG, have been differentiated by complementation analysis. These can give rise to isolated methylmalonic acidemia (cblA, cblB, cblD variant 2), isolated hyperhomocysteinemia (cblD variant 1, cblE, cblG) or combined methylmalonic acidemia and hyperhomocysteinemia (cblC, classic cblD, cblF). All these disorders are inherited as autosomal recessive traits. The genes underlying each of these disorders have been identified. Two other disorders, haptocorrin deficiency and transcobalamin receptor deficiency, have been described, but it is not clear that they have any consistent clinical phenotype.

show abstract

“…The patients with treatment failure presented with cognitive decline, visual dysfunction from maculopathy, and proprioceptive difficulties from presumed dorsal column involvement of the spinal cord. Symptoms improved when IM therapy was resumed (Schiff et al 2010). …”

Section: Discussionmentioning

confidence: 99%

Expanding the Spectrum of Methylmalonic Acid-Induced Pallidal Stroke: First Reported Case of Metabolic Globus Pallidus Stroke in Transcobalamin II Deficiency

et al. 2013

View full text Add to dashboard Cite

A 10-year-old boy with transcobalamin II (TCII) deficiency on oral cyanocobalamin therapy presented with acute right hemiparesis and sensory axonal neuropathy in the context of an intercurrent viral illness. MRI demonstrated unilateral globus pallidus stroke with normal MRA. Echocardiogram was normal. Methylmalonic acid in serum was mildly elevated at 10.29 mmol/L (normal < 0.37 mmol/L), which was an 18-fold increase from his previous baseline. The patient was switched to IM cyanocobalamin and serum methylmalonic acid levels normalized over 6 months to 0.01 mmol/L. After 4 months of IM cyanocobalamin therapy, the neuropathy had resolved. Repeat MRI 4 months after the sentinel stroke demonstrated a chronicappearing contralateral globus pallidus stroke of uncertain timing.Conclusions: We are describing the first case of metabolic stroke and peripheral neuropathy in TCII deficiency. The neuropathy was responsive to parenteral hydroxycobalamin. Unilateral globus pallidus stroke in the appropriate clinical context should not exclude a metabolic etiology as it may herald contralateral involvement and may provide an opportunity for early recognition and treatment.

show abstract

Should transcobalamin deficiency be treated aggressively?

Cited by 33 publications

References 24 publications

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Inborn errors of cobalamin absorption and metabolism

Expanding the Spectrum of Methylmalonic Acid-Induced Pallidal Stroke: First Reported Case of Metabolic Globus Pallidus Stroke in Transcobalamin II Deficiency

Contact Info

Product

Resources

About