Thiamine responsive megaloblastic anemia: The puzzling phenotype

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Thiamine responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type 1 diabetes mellitus and sensorineural deafness. Other clinical findings have been described in few cases. The SLC19A2 gene on chromosome 1q 23.3 is implicated in all cases with TRMA. Our aim is to discuss the clinical manifestations of all Omani children diagnosed with TRMA and determine genotype-phenotype relationship. Procedure: Clinical and laboratory data of all patients diagnosed in Oman were retrospectively collected. Mutation analysis of affected families was conducted using two Microsatellite markers. Genotyping was performed with fluorescent-labeled PCR primers. To define the deletion breakpoint region, PCR reactions were carried out using different primer pairs located at the introns 3 and 3′-untranslated region with Expand Long Template PCR kit. Results: A total of six children have been diagnosed with this syndrome. They were five females and one male. They all presented with sensorineural deafness at birth while the age of anemia presentation ranged between 6 weeks to 19 months. They all belong to same family with complex interfamilial marriages and presented with the typical triad. Of interest is the very rare presentation of one patient with Uhl cardiac anomaly (total absence of right ventricular myocardium with apposition of endocardium and pericardium) that has never been described before in patients with TRMA. All patients have a novel large deletion of 5,224bp involving exons 4, 5, and 6 of SLC19A2. Conclusions: TRMA is a disease of expanding phenotypic spectrum with poor genotype-phenotype correlation.

Original languageEnglish
Pages (from-to)528-531
Number of pages4
JournalPediatric Blood and Cancer
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Megaloblastic Anemia
Thiamine
Phenotype
Deafness
Polymerase Chain Reaction
Oman
Endocardium
Pericardium
Genetic Association Studies
3' Untranslated Regions
Marriage
Microsatellite Repeats
Introns
Anemia
Exons
Myocardium
Diabetes Mellitus
Chromosomes
Genotype
Parturition

Keywords

  • SLC19A2 gene
  • TRMA
  • Uhl anomaly

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Thiamine responsive megaloblastic anemia : The puzzling phenotype. / Beshlawi, Ismail; Zadjali, Shoaib Al; Bashir, Wafa; Elshinawy, Mohamed; Alrawas, Abdulhakim; Wali, Yasser.

In: Pediatric Blood and Cancer, Vol. 61, No. 3, 03.2014, p. 528-531.

Research output: Contribution to journalArticle

@article{c9e5b23604e74842993ecd9945f4f030,
title = "Thiamine responsive megaloblastic anemia: The puzzling phenotype",
abstract = "Background: Thiamine responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type 1 diabetes mellitus and sensorineural deafness. Other clinical findings have been described in few cases. The SLC19A2 gene on chromosome 1q 23.3 is implicated in all cases with TRMA. Our aim is to discuss the clinical manifestations of all Omani children diagnosed with TRMA and determine genotype-phenotype relationship. Procedure: Clinical and laboratory data of all patients diagnosed in Oman were retrospectively collected. Mutation analysis of affected families was conducted using two Microsatellite markers. Genotyping was performed with fluorescent-labeled PCR primers. To define the deletion breakpoint region, PCR reactions were carried out using different primer pairs located at the introns 3 and 3′-untranslated region with Expand Long Template PCR kit. Results: A total of six children have been diagnosed with this syndrome. They were five females and one male. They all presented with sensorineural deafness at birth while the age of anemia presentation ranged between 6 weeks to 19 months. They all belong to same family with complex interfamilial marriages and presented with the typical triad. Of interest is the very rare presentation of one patient with Uhl cardiac anomaly (total absence of right ventricular myocardium with apposition of endocardium and pericardium) that has never been described before in patients with TRMA. All patients have a novel large deletion of 5,224bp involving exons 4, 5, and 6 of SLC19A2. Conclusions: TRMA is a disease of expanding phenotypic spectrum with poor genotype-phenotype correlation.",
keywords = "SLC19A2 gene, TRMA, Uhl anomaly",
author = "Ismail Beshlawi and Zadjali, {Shoaib Al} and Wafa Bashir and Mohamed Elshinawy and Abdulhakim Alrawas and Yasser Wali",
year = "2014",
month = "3",
doi = "10.1002/pbc.24849",
language = "English",
volume = "61",
pages = "528--531",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Thiamine responsive megaloblastic anemia

T2 - The puzzling phenotype

AU - Beshlawi, Ismail

AU - Zadjali, Shoaib Al

AU - Bashir, Wafa

AU - Elshinawy, Mohamed

AU - Alrawas, Abdulhakim

AU - Wali, Yasser

PY - 2014/3

Y1 - 2014/3

N2 - Background: Thiamine responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type 1 diabetes mellitus and sensorineural deafness. Other clinical findings have been described in few cases. The SLC19A2 gene on chromosome 1q 23.3 is implicated in all cases with TRMA. Our aim is to discuss the clinical manifestations of all Omani children diagnosed with TRMA and determine genotype-phenotype relationship. Procedure: Clinical and laboratory data of all patients diagnosed in Oman were retrospectively collected. Mutation analysis of affected families was conducted using two Microsatellite markers. Genotyping was performed with fluorescent-labeled PCR primers. To define the deletion breakpoint region, PCR reactions were carried out using different primer pairs located at the introns 3 and 3′-untranslated region with Expand Long Template PCR kit. Results: A total of six children have been diagnosed with this syndrome. They were five females and one male. They all presented with sensorineural deafness at birth while the age of anemia presentation ranged between 6 weeks to 19 months. They all belong to same family with complex interfamilial marriages and presented with the typical triad. Of interest is the very rare presentation of one patient with Uhl cardiac anomaly (total absence of right ventricular myocardium with apposition of endocardium and pericardium) that has never been described before in patients with TRMA. All patients have a novel large deletion of 5,224bp involving exons 4, 5, and 6 of SLC19A2. Conclusions: TRMA is a disease of expanding phenotypic spectrum with poor genotype-phenotype correlation.

AB - Background: Thiamine responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type 1 diabetes mellitus and sensorineural deafness. Other clinical findings have been described in few cases. The SLC19A2 gene on chromosome 1q 23.3 is implicated in all cases with TRMA. Our aim is to discuss the clinical manifestations of all Omani children diagnosed with TRMA and determine genotype-phenotype relationship. Procedure: Clinical and laboratory data of all patients diagnosed in Oman were retrospectively collected. Mutation analysis of affected families was conducted using two Microsatellite markers. Genotyping was performed with fluorescent-labeled PCR primers. To define the deletion breakpoint region, PCR reactions were carried out using different primer pairs located at the introns 3 and 3′-untranslated region with Expand Long Template PCR kit. Results: A total of six children have been diagnosed with this syndrome. They were five females and one male. They all presented with sensorineural deafness at birth while the age of anemia presentation ranged between 6 weeks to 19 months. They all belong to same family with complex interfamilial marriages and presented with the typical triad. Of interest is the very rare presentation of one patient with Uhl cardiac anomaly (total absence of right ventricular myocardium with apposition of endocardium and pericardium) that has never been described before in patients with TRMA. All patients have a novel large deletion of 5,224bp involving exons 4, 5, and 6 of SLC19A2. Conclusions: TRMA is a disease of expanding phenotypic spectrum with poor genotype-phenotype correlation.

KW - SLC19A2 gene

KW - TRMA

KW - Uhl anomaly

UR - http://www.scopus.com/inward/record.url?scp=84892550614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892550614&partnerID=8YFLogxK

U2 - 10.1002/pbc.24849

DO - 10.1002/pbc.24849

M3 - Article

C2 - 24249281

AN - SCOPUS:84892550614

VL - 61

SP - 528

EP - 531

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 3

ER -