Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent

Abstract

Thiamine responsive megaloblastic anemia syndrome, an autosomal recessive inherited disorder characterized by a triad of anemia, diabetes mellitus and sensorineural deafness is caused by a deficiency of a thiamine transporter protein. The disorder is rare and has not been reported from our community which has high background of consanguinity. We report a six years old girl who presented with diabetes mellitus which remitted after thiamine replacement. The girl in addition had sensorineural deafness, reinopathy, atrial septal defect and megaloblastic anemia which responded to high doses of thymine. This is the first case reported from Kashmir valley and third from India. The presentation and management in such cases is discussed.

Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults

“…Other, more variable features include optic atrophy, congenital heart defects, short stature, and significant neurological deficits such as stroke and epilepsy during infancy (77, 86). The term “thiamine-responsive” refers to the observation of clinical, symptomatic improvement after administration of high doses of thiamine (86, 87).…”

Stroke-like Episodes in Inherited Neurometabolic Disorders

“…Mutation in the SLC19A2 gene is associated with loss-of-function in plasma membrane thiamine-transporter I. Vitamin B1 is transported into cells via two transporters: THTR1, associated with the SLC19A2 gene, and THTR2, which is encoded by the SLC19A3 gene. Loss-of-function mutation of SCL19A2 is connected with dysfunction of pancreatic beta-islet cells, ear cells and stem cells of hematopoiesis due to high expression of THTR1 thiamine transporter on aforementioned units [ 81 , 82 , 83 , 84 , 85 ]. TRMA is commonly diagnosed during infancy or early childhood.…”

“…Neurological manifestations are observed in 20–40 % of patients with TRMA in their early childhood [ 81 , 82 , 87 , 88 ]. THTR2 transporter seems to be more essential for thiamine brain active transport than the THTR1 channel [ 88 , 90 ] ( Table 4 ) [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Review: Understanding Rare Genetic Diseases in Low Resource Regions Like Jammu and Kashmir – India

“…There are further series of case reports on RDs including Ellis-van Creveld Syndrome, Epidermolysis Bullosa, Fabry's disease, Fahr's disease, Hereditary Stomatocytosis, Holt-Oram Syndrome, Ollier's disease, different types of Porphyria, Rogers Syndrome, Wolfram syndrome, congenital anomalies, and many more from different regions of J&K (Bhat J. I. et al, 2010;Bhat Y. J. et al, 2010;Bhat et al, 2015;Qayoom et al, 2010;Ganie et al, 2011Ganie et al, , 2012Majid et al, 2012;Shoib et al, 2012;Hassan and Keen, 2013;Rasool et al, 2015;Wani et al, 2016;Kumar S. et al, 2017;Nazir and Chalkoo, 2017;Ilyas et al, 2019). Most of these are merely presented as case reports and the underpinning molecular etiology of many of the reported as well as unreported RDs cases from J&K have been due for years.…”