Novel mutation in the SLC19A2 gene in an African‐American female with thiamine‐responsive megaloblastic anemia syndrome

Abstract

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine-responsive anemia. Mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter protein THTR-1 are responsible for the clinical features associated with TRMA syndrome. We report an African-American female with TRMA-syndrome associated with thyroid disease and retinitis pigmentosa caused by a novel mutation in the SLC19A2 gene. The patient presented at 12 months of age with paroxysmal atrial tachycardia and hepatosplenomegaly. One month later, she developed DM requiring intermittent insulin therapy. At 2-1/2 years of age, profound sensorineural hearing loss was discovered. By 4 years of age, daily insulin therapy (0.5 U/kg/day) was instituted and her insulin requirement gradually increased to 1.0 U/kg/day by 9 years of age. She developed optic atrophy, retinitis pigmentosa, and visual impairment by 12 years of age with severe restriction of peripheral vision by 16 years. At age 19, a thiamine-responsive normocytic anemia was discovered. She was diagnosed with autoimmune thyroiditis at 20 years and she experienced a psychotic episode associated with a mood disorder at age 21. With oral thiamine therapy, her insulin requirement decreased by 30% over a 20 month period. Molecular analysis revealed that the patient is homozygous for a missense mutation (C152T) in exon 1 of the SLC19A2 gene.

Anemia in a Child with Deafness: Be Vigilant for a Rare Cause!

“…This mutation has previously been described in three children from two consanguineous families from Pakistan [3].Diabetes mellitus is non-type 1 in nature with onset from infancy to adolescence. Decrease in insulin requirement with institution of high-dose of thiamine has been reported [4]. This was observed in our case also.…”

Thiamine transporter mutation: an example of monogenic diabetes mellitus

“…In 1978, a second case was reported by Viana & Carvalho (7). Since then, a number of cases have been described (4,(8)(9)(10)(11)(12)(13). It was postulated that this syndrome is related to defects in thiamine metabolism (1,7,14).…”

Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation

“…4,27,[56][57][58][59] Although mutations in SLC19A2 are one of the causes of PNDM, 1 the clinical diagnosis of SLC19A2 deficiency is rarely made until the presentation of all syndromic symptoms (i.e. diabetes, anemia, and deafness) and is sometimes unrecognized among patients with early onset diabetes.…”

“…diabetes, anemia, and deafness) and is sometimes unrecognized among patients with early onset diabetes. 28,56 Because deafness was the earliest symptoms diagnosed in the disease, reflecting the fact that hearing loss is more recognizable than anemia and diabetes, the results of newborn hearing tests could aid in the differential diagnosis of SLC19A2 deficiency among patients with PNDM to permit an earlier diagnosis, proper treatment, and less mortality. 52,60,61 It has been shown that despite thiamine treatment, insulin dependency can relapse after adolescence in some SLC19A2-deficient patients.…”