An Italian case series' description of thiamine responsive megaloblastic anemia syndrome: importance of early diagnosis and treatment

Abstract

Background: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations.

Cases presentation: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed.

Conclusions: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

Keywords: Case series; Nonautoimmune diabetes; Optic atrophy; Sensorineural deafness; Thiamine-responsive megaloblastic anemia syndrome.

Fig. 1

Case 1 ambulatory glucose profile report. Glycaemic control recorded by RT-CGM one week after switching from insulin therapy to oral thiamine therapy

Fig. 2

Color fundus photographs of the left eye of the older sister acquired in January 2011. Only the left was available, and the images were not centred on the posterior pole due to nystagmus. A: Color fundus picture of the nasal retinal sector showing optic disc pallor and attenuation of the retinal vessels. B: Color fundus picture of the inferior retinal sector showing bone-spicule pigment deposits in the mid periphery)

Fig. 3

Spectral-domain optical coherence tomography (SD-OCT) of the older sister performed in September 2020. A: SD-OCT perifoveal B-scan of the right eye revealing vitreo-macular traction syndrome and epiretinal membrane (ERM) along with severe outer retinal layers and retinal pigment epithelium (RPE) atrophy. B: SD-OCT foveal B-scan of the left eye showing ERM and severe outer retinal layers and RPE atrophy)

Fig. 4

Colour fundus photographs of the right eye (RE) and left eye (LE) of the younger sister acquired in September 2020. A and B: right eye (RE) and and left eye (LE) colour fundus photographs showing mild disk pallor, with preserved retinal vessel calibre and foveal reflex

Fig. 5

Spectral-domain optical coherence tomography, fundus autofluorescence of the younger sister acquired in September 2020. A and B: RE and LE FAF revealing a normal autofluorescence of the posterior pole. C and D: RE and LE SD-OCT showing an integrity of the inner and outer retinal layers and a normal reflectivity of the retinal pigment epithelium)