Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report (original) (raw)
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Thiamine-responsive megaloblastic anemia syndrome: a novel mutation
Genetic counseling, 2012
The thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss due to mutations in SLC 19A2 that encodes a thiamine transporter protein. The disease can manifest at any time between infancy and adolescence, and not all cardinal findings are present initially. The anemia typically improves significantly with pharmacological doses of thiamine. Variable improvement in diabetes is also noted. However, the hearing loss is apparently irreversible, although a delay in the onset of deafness may be possible. We present a 2-year old girl with non-autoimmune diabetes mellitus and anemia in whom we found a novelc.95T>A (leu32X) mutation in the SLC19A2 gene in this study.Our patient with this new mutation did not suffer from hearing loss.
Thiamine-responsive megaloblastic anemia: early diagnosis may be effective in preventing deafness
2015
Thiamine-responsive megaloblastic anemia syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss. Mutations in the SLC19A2 gene, encoding a high-affinity thiamine transporter protein, THTR-1, are responsible for the clinical features associated with thiamine-responsive megaloblastic anemia syndrome in which treatment with pharmacological doses of thiamine correct the megaloblastic anemia and diabetes mellitus. The anemia can recur when thiamine is withdrawn. Thiamine may be effective in preventing deafness if started before two months. Our patient was found homozygous for a mutation, 242insA, in the nucleic acid sequence of exon B, with insertion of an adenine introducing a stop codon at codon 52 in the high-affinity thiamine transporter gene, SLC19A2, on chromosome 1q23.3. Key words: thiamine-responsive megaloblastic anemia, diabetes mellitus, deafness. Thiamine-responsive megaloblastic anemia (TRMA; OMIM 2...
Ibnosina Journal of Medicine and Biomedical Sciences
Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and ...
A long-term follow-up of a case of Rogers syndrome, Thiamine responsive megaloblastic anemia
International Journal of Contemporary Pediatrics
Thiamine-responsive megaloblastic anemia (TRMA) also known as Rogers syndrome is a rare autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus, and progressive sensorineural deafness. The disease can be manifested anytime between infancy and adolescence, and all the cardinal findings may not be present at the time of the diagnosis. The main defect lies in the active thiamine uptake into cells which is disturbed. Not many cases have been reported about the long-term follow-up of children with this disorder and their associated complications. We hereby report a 14 years follow-up of a girl with Rogers syndrome diagnosed at toddler age with nonresponsive anemia and diabetes and further progressed to have sensorineural hearing loss. Her clinical exome study showed a mutation in the SLC19A2 gene. This experience illustrates the relevance of a detailed evaluation and regular follow-up to assess the progression of the syndrome till her pubertal age.
Novel Mutation in the SLC19A2 Gene in Thiamine-Responsive Megaloblastic Anemia (Rogers’ Syndrome)
Iranian Journal of Neonatology IJN, 2012
Introduction: The Thiamine Transporter gene SLC19A2 is the only gene known to be associated with TRMA. This syndrome is a trial clinical characterized by megaloblastic anemia, nonautoimmune diabetes mellitus and sensory-neural hearing loss. Methods: Described here are three children from consanguineous Iranian families with thiamine – responsive megaloblastic anemia (TRMA) or Rogers' syndrome. Case one and two were siblings of healthy first-cousin parents and case three from a healthy second-cousin couple. These cases presented with hyperglycemia, anemia, and hearing loss. Thiamine reversed the anemia and there was a satisfactory response for the hyperglycemia as well. Results: In all three patients, direct sequencing revealed a homozygous mutation c.38 G>A (P.E.128K) resulting in the substitution of glutamic acid to lysine at position 128 in exon 2 of the SLC19A2 gene on chromosome 1q23.3. This novel mutation was confirmed by the PCR RFLP assay of more than 100 contro...
Pediatric Blood & Cancer, 2013
The syndrome of diabetes mellitus, sensorineural deafness and megaloblastic anemia dose not result from thiamine deficiency. The previous reported patients had no sign of beriberi, had normal nutrition, and had no evidence of malabsorption. The features of this syndrome with apparent inheritance of autosomal recessive trait may define this puzzling syndrome as a true thiamine dependency state. The first Iranian patient was described by Vossough et al. in 1995. We found nine new cases with diagnostic criteria of thiamine responsive megaloblastic anemia during eight years of our study. In two patients, presentation of diabetes and anemia was concomitant. All of them were deaf with sensorineural hearing loss which was detected in infancy up to two years of age. The presence of congenital valvular heart disease was eliminated by normal echocardiography, but cardiomyopathy was discovered in two. Nonspecific amino-aciduria was discovered in three but urinary screening tests for hereditary orotic aciduria were negative. Ox-Phos biochemistry of muscle mitochondria which demonstrates severe defect in complexes I, III, IV in diabetes mellitus associated with deafness, were done but was unremarkable in our patients. Urinary methylmalonic acid and methyl malonyl carnitine by GS/MS and TMS was done in our patients and showed abnormal results in six patients. Thiamine gene, SLC 19A2, was detected in four patients.
Journal of Pediatrics, 1978
A 6-)'ear-old girl is described who has congenital megaloblastic anemia which completel)" responded onl)' tO pharmacologic doses of ihiamine. Relapse was observed twice when the drug was discontinued. The rehztroduction of thiamine caused a prompt reticuloc)'tosis and a rise hi hemoglobin concentration. Other abnormalities included latent diabetes mellitas, sensorineural deafness, and "'situs iltversus totalis." ller parents are first cousins, both with partial deafness. Her father has an abnormal oral ghtcose tolerance test. A single shnilar case has been reported; the combination of abnost the same anomalies seems to represent a newl)" recognized s)'ndrome. This case rehlforces the proposal that thiamine has a role #z hematopoiesis.