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Novel mutation in the SLC19A2 gene in an Iranian family with thiamine-responsive megaloblastic anemia: a series of three cases.

Ghaemi N, Ghahraman M, Abbaszadegan MR, Baradaran-Heravi A, Vakili R - J Clin Res Pediatr Endocrinol (2013)

Bottom Line: This mutation results in the substitution of glutamic acid to lysine at position 128 in exon 2 and was not detected in 200 control chromosomes.Thiamine therapy reversed the anemia and alleviated the hyperglycemia in all three patients.We recommend sequence analysis of the SLC19A2 gene in individuals with a clinical triad of diabetes mellitus, hearing loss, and anemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Endocrinology, Imam Reza Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. E-mail: vakilir@mums.ac.ir.

ABSTRACT
Thiamine-responsive megaloblastic anemia (TRMA) is a clinical triad characterized by megaloblastic anemia, non-autoimmune diabetes mellitus, and sensory-neural hearing loss. Mutations in the thiamine transporter gene, solute carrier family 19, member 2 (SLC19A2), have been associated with TRMA. Three pediatric patients from a large consanguineous Iranian family with hyperglycemia, anemia, and hearing loss were clinically diagnosed with TRMA. In all three patients, TRMA was confirmed by direct sequencing of the SLC19A2 gene that revealed a novel missense homozygous mutation c.382 G>A (p.E128K). This mutation results in the substitution of glutamic acid to lysine at position 128 in exon 2 and was not detected in 200 control chromosomes. Thiamine therapy reversed the anemia and alleviated the hyperglycemia in all three patients. We recommend sequence analysis of the SLC19A2 gene in individuals with a clinical triad of diabetes mellitus, hearing loss, and anemia. The administration of thiamine ameliorates the megaloblastic anemia and the hyperglycemia in patients with TRMA.

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Related in: MedlinePlus

Family pedigree and SLC19A2 mutation analysis: A. The pedigree of the large consanguineous family with TRMA; B. The DNA sequencing chromatograms showing a G to A transition at codon sequence 382 in exon 2 of the SLC19A2 gene; Patients are homozygous for the mutation and the healthy members of the families are heterozygous
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f1: Family pedigree and SLC19A2 mutation analysis: A. The pedigree of the large consanguineous family with TRMA; B. The DNA sequencing chromatograms showing a G to A transition at codon sequence 382 in exon 2 of the SLC19A2 gene; Patients are homozygous for the mutation and the healthy members of the families are heterozygous

Mentions: The propositus was the second child of healthy first-cousin parents. Hearing loss was noted since he was six months of age. The patient was referred to our hospital with growth restriction, megaloblastic anemia (Hb 10.1 g/dL, MCV 97.2) and hyperglycemia (FBS 191 mg/dL) at the age of 16 months. Audiometry revealed deep sensorineural hearing loss. Clinical diagnosis of TRMA was suspected and confirmed by DNA sequencing of the coding exons of the SLC19A2 gene. This revealed a novel homozygous mutation c.382G>A resulting in the substitution of glutamic acid to lysine at position 128 (p.E128K) of the SLC19A2 protein. Healthy members of the family including parents and a younger brother were heterozygous for this mutation (Figure 1). The c.382G>A missense mutation was absent in 200 unrelated control alleles confirmed by polymerase chain reaction followed by restriction fragment length polymorphism. Thiamine therapy ameliorated the patient’s anemia and hyperglycemia. In the patient’s most recent visit, his growth status, his hemoglobin and blood glucose levels were normal (Table 1).


Novel mutation in the SLC19A2 gene in an Iranian family with thiamine-responsive megaloblastic anemia: a series of three cases.

Ghaemi N, Ghahraman M, Abbaszadegan MR, Baradaran-Heravi A, Vakili R - J Clin Res Pediatr Endocrinol (2013)

Family pedigree and SLC19A2 mutation analysis: A. The pedigree of the large consanguineous family with TRMA; B. The DNA sequencing chromatograms showing a G to A transition at codon sequence 382 in exon 2 of the SLC19A2 gene; Patients are homozygous for the mutation and the healthy members of the families are heterozygous
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814536&req=5

f1: Family pedigree and SLC19A2 mutation analysis: A. The pedigree of the large consanguineous family with TRMA; B. The DNA sequencing chromatograms showing a G to A transition at codon sequence 382 in exon 2 of the SLC19A2 gene; Patients are homozygous for the mutation and the healthy members of the families are heterozygous
Mentions: The propositus was the second child of healthy first-cousin parents. Hearing loss was noted since he was six months of age. The patient was referred to our hospital with growth restriction, megaloblastic anemia (Hb 10.1 g/dL, MCV 97.2) and hyperglycemia (FBS 191 mg/dL) at the age of 16 months. Audiometry revealed deep sensorineural hearing loss. Clinical diagnosis of TRMA was suspected and confirmed by DNA sequencing of the coding exons of the SLC19A2 gene. This revealed a novel homozygous mutation c.382G>A resulting in the substitution of glutamic acid to lysine at position 128 (p.E128K) of the SLC19A2 protein. Healthy members of the family including parents and a younger brother were heterozygous for this mutation (Figure 1). The c.382G>A missense mutation was absent in 200 unrelated control alleles confirmed by polymerase chain reaction followed by restriction fragment length polymorphism. Thiamine therapy ameliorated the patient’s anemia and hyperglycemia. In the patient’s most recent visit, his growth status, his hemoglobin and blood glucose levels were normal (Table 1).

Bottom Line: This mutation results in the substitution of glutamic acid to lysine at position 128 in exon 2 and was not detected in 200 control chromosomes.Thiamine therapy reversed the anemia and alleviated the hyperglycemia in all three patients.We recommend sequence analysis of the SLC19A2 gene in individuals with a clinical triad of diabetes mellitus, hearing loss, and anemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Endocrinology, Imam Reza Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. E-mail: vakilir@mums.ac.ir.

ABSTRACT
Thiamine-responsive megaloblastic anemia (TRMA) is a clinical triad characterized by megaloblastic anemia, non-autoimmune diabetes mellitus, and sensory-neural hearing loss. Mutations in the thiamine transporter gene, solute carrier family 19, member 2 (SLC19A2), have been associated with TRMA. Three pediatric patients from a large consanguineous Iranian family with hyperglycemia, anemia, and hearing loss were clinically diagnosed with TRMA. In all three patients, TRMA was confirmed by direct sequencing of the SLC19A2 gene that revealed a novel missense homozygous mutation c.382 G>A (p.E128K). This mutation results in the substitution of glutamic acid to lysine at position 128 in exon 2 and was not detected in 200 control chromosomes. Thiamine therapy reversed the anemia and alleviated the hyperglycemia in all three patients. We recommend sequence analysis of the SLC19A2 gene in individuals with a clinical triad of diabetes mellitus, hearing loss, and anemia. The administration of thiamine ameliorates the megaloblastic anemia and the hyperglycemia in patients with TRMA.

Show MeSH
Related in: MedlinePlus