Transcobalamin II deficiency: Case report and review of the literature

Kaikov, Yigal; Wadsworth, Louis D.; Hall, Charles A.; Rogers, Paul C.

doi:10.1007/bf01955004

Cited by 41 publications

(20 citation statements)

References 20 publications

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“…This autosomal recessive disorder presents with failure to thrive, mucosal ulceration, vomiting, diarrhoea, lethargy, irritability and occasionally immunological dysfunction. The haematological features include; pancytopenia, macrocytic anaemia, neutropenia, reticulocytopenia, and megaloblastic bone marrow (Hakami et al 1971;Kaikov et al 1991).…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…TCII deficiency is an autosomal recessive condition resulting from mutations in the TCN2 gene on chromosome 22q12 (Watkins and Rosenblatt 2011;Regec et al 1995). It typically presents in the first 2 months of life with pancytopenia, failure to thrive, and gastrointestinal symptoms (Kaikov et al 1991;Gimpert et al 1975). Laboratory markers typically include increased homocysteine, reduced methionine, increased methylmalonic acid, metabolic acidosis, and megaloblastic anemia (Kaikov et al 1991).…”

Section: Discussionmentioning

confidence: 99%

“…It typically presents in the first 2 months of life with pancytopenia, failure to thrive, and gastrointestinal symptoms (Kaikov et al 1991;Gimpert et al 1975). Laboratory markers typically include increased homocysteine, reduced methionine, increased methylmalonic acid, metabolic acidosis, and megaloblastic anemia (Kaikov et al 1991). Stroke and peripheral neuropathy have not previously been reported in association with TCII deficiency.…”

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

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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.

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“…Typically, symptoms of vitamin B 12 deficiency include poor feeding, weight loss and irritability; glossitis and infections have also been reported. 14,15 It is the neurologic manifestations, however, that are the most concerning. As illustrated by the two infants we described, central nervous system symptoms can be severe, beginning with irritability, apathy, lethargy and gross motor developmental regression.…”

Section: Clinical Presentationmentioning

confidence: 99%

Vitamin B₁₂ deficiency in infants secondary to maternal causes

Roumeliotis

Dix

Lipson

2012

CMAJ

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A nine-month-old female infant presented with a two-day history of vomiting, diarrhea and decreased urine output, along with a three-month history of lethargy and reduced tone. Her early development had been normal, but regression of skills had begun three months before presentation, with a loss of gross motor skills progressing to a loss of head control. The child had been exclusively breastfed until solids were slowly introduced over the last month. Her family was of South-East Asian ethnic origin, and her mother was a strict life-long vegan who took prenatal vitamins during pregnancy.On examination, the baby was sleepy and pale. Her weight was 6.65 kg (< 3rd percentile), height was 69 cm (25th percentile) and head circumference was 41 cm (< 3rd percentile). The liver edge was 3 cm below the costal margin. The splenic tip was palpable. Her axial and peripheral muscle tone was decreased, with frog-like posture of both legs. No antigravity power was exhibited. Reflexes were 3+ in her lower extremities and 2+ in her upper extremities. She was able to fix visually but did not follow.Laboratory investigations showed a hemo- /L. The blood smear showed pancytopenia with severe leukoerythroblastic change, dysplastic red blood cells and rare hypersegmented neutrophils; it appeared severely megaloblastic overall (Figure 1). The albumin level was 18 (range 34-42) g/L. Vitamin B 12 level was less than 37 (range 133-695) pmol/L (lower reporting limit), and the folate level was 14 (range 7-36) nmol/L. A bone marrow biopsy showed morphological changes consistent with megaloblastic anemia. Magnetic resonance imaging (MRI) of the patient's brain showed generalized atrophy. Metabolic and biochemical investigations, including acylcarnitine profile, plasma amino acid and urine organic acids, showed abnormalities consistent with dietary protein deficiency.Because the infant had been mostly breastfed with limited solid intake, we examined the mother. Her complete blood count was normal, but her vitamin B 12 level was low at 63 (adult reference range 133-695, deficient < 107) pmol/L. Review of the mother's prenatal blood work indicated a normal hemoglobin level, with a normal mean corpuscular volume.The infant's anemia was managed initially with a slow transfusion of packed red blood cells. Intramuscular injections of vitamin B 12 (1000 µg) were given daily for seven days, then weekly for the next month, along with oral iron supplementation. Nasogastric feeding with formula was initiated because of poor suck, and breastfeeding was maintained for comfort. The mother was started on oral B 12 supplementation.Five months later, the infant was consuming solid baby food and infant formula, and her growth parameters had improved. Her muscle tone and neurologic status had also improved. The complete blood count and B 12 levels were normal. • Infant B 12 sufficiency is related to maternal levels via neonatal stores at birth and the amount in breast milk. Cases Vitamin• Vitamin B 12 deficiency in infants, although rare, is important to recogn...

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Transcobalamin II deficiency: Case report and review of the literature

Cited by 41 publications

References 20 publications

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

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

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

Vitamin B₁₂ deficiency in infants secondary to maternal causes

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Transcobalamin II deficiency: Case report and review of the literature

Cited by 41 publications

References 20 publications

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

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

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

Vitamin B12 deficiency in infants secondary to maternal causes

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Vitamin B₁₂ deficiency in infants secondary to maternal causes