A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia.

BACKGROUND/AIMS: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. METHODS: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1-3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband's and his brother's clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband's whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). RESULTS: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband's whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. CONCLUSIONS: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.

Thiamine-responsive megaloblastic anemia (TRMA) in an Austrian boy with compound heterozygous SLC19A2 mutations.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare disorder typically characterized by megaloblastic anemia, non-type I diabetes and sensorineural deafness. It is caused by various mutations in the SLC19A2 gene that impair the encoded thiamine transporter. So far, only 70 affected individuals mainly from consanguineous families of Middle and Far Eastern origin with a wide spectrum of signs and symptoms, variable onset of disease, and primarily homozygote mutations in SLC19A2 have been reported. We present the first genuine central European descendent with combined heterozygote mutations in SLC19A2, an Austrian boy suffering from pancytopenia and non-type I diabetes. Both manifestations resolved completely under continuous oral thiamine supplementation. Our observation underlines that despite its rarity, TRMA must be considered as an important differential diagnosis in native central European patients with suggestive signs and symptoms. An early molecular genetic verification of the diagnosis provides a sound basis for a successful and simple treatment that helps to prevent severe sequelae.

Pregnancy- and lactation-related folate deficiency in South Africa--a case for folate food fortification.

OBJECTIVE: Characterisation of patients presenting with megaloblastic anaemia according to clinical, sociological, haematological and aetiological aspects of their disease, and use of these findings to increase awareness among clinicians and to make recommendations regarding changes in national health policy. METHODS: This study included 104 patients presenting with megaloblastic anaemia to a large referral hospital over a 1-year period. Data were collected and analysed in terms of age, gender, parity, gravidity, duration of lactation, socio-economic status, geographical origins, diet, previous haematinic treatment, clinical presentation and haematological measurements. RESULTS: The most common cause of megaloblastic anaemia was pernicious anaemia or probable pernicious anaemia (50%), followed by pregnancy- and lactation-related folate deficiency (32%); of these patients, the majority (28) presented postpartum while lactating; 5 patients were in the immediate puerperal period of 6 weeks, and a further 16 were seen during the first year and 7 during the second year following delivery. Only 4 patients were pregnant, and it is noteworthy that 2 of these were still lactating at 34 weeks' gestation. CONCLUSION: Pregnancy- and lactation-related folate deficiency up to 2 years after delivery remains a common cause of megaloblastic anaemia in South Africa. Certain communities in rural South Africa have recently been shown to have high incidences of both neural tube defects and folate deficiency. The fortification of a staple food (e.g. maize or flour) with folic acid is feasible, inexpensive, safe and likely to be beneficial. This practice should reduce the prevalences of megaloblastic anaemia in fertile women, neural tube defects, other congenital abnormalities, intra-uterine growth retardation, prematurity and possibly cardiovascular disease. There is urgent need for a national policy in this regard.