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 deficiency and cardiac dysfunction in Cambodian infants.

OBJECTIVES: To compare blood thiamine concentrations, echocardiography findings, and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in infants with clinically diagnosed beriberi and healthy matched controls, and to evaluate changes after thiamine treatment. STUDY DESIGN: Sixty-two Cambodian infants (20 cases and 42 controls), aged 2-47 weeks, were enrolled in this prospective study. Echocardiography and phlebotomy were performed at baseline and after thiamine treatment. RESULTS: Both cases and controls were thiamine-deficient, with median blood thiamine diphosphate (TDP) concentrations of 47.6 and 55.1 nmol/L, respectively (P = .23). All subjects had normal left ventricular ejection fraction. The median NT-proBNP concentration in cases (340 pg/mL [40.1 pmol/L]) was higher than previously reported normal ranges, but not statistically significantly different from that in controls (175 pg/mL [20.7 pmol/L]) (P = .10), and was not correlated with TDP concentration (P = .13). Two cases with the lowest baseline TDP concentrations (24 and 21 nmol/L) had right ventricular enlargement and elevated NT-proBNP levels that improved dramatically by 48 hours after thiamine administration. CONCLUSION: Only a minority of thiamine-deficient Cambodian infants demonstrate abnormal echocardiography findings. Thiamine deficiency produces echocardiographic evidence of right ventricular dysfunction, but this evidence is not apparent until deficiency is severe. NT-proBNP concentrations are mildly elevated in sick infants with normal echocardiography findings, indicating possible physiological changes not yet associated with echocardiographic abnormalities.

Thiamine nutritional status and depressive symptoms are inversely associated among older Chinese adults.

Thiamine has been hypothesized to play an important role in mental health; however, few studies have investigated the association between thiamine nutritional status and depression in the general population. Concentrations of free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men and women aged 50-70 y. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score of ≥16. The median erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and 169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower concentrations of all 3 erythrocyte thiamine biomarkers were monotonically associated with a higher prevalence of depressive symptoms: the multivariable adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI = 1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P-trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP. In conclusion, poorer thiamine nutritional status and higher odds of depressive symptoms were associated among older Chinese adults. This finding should be further investigated in prospective or interventional studies.

Malnutrition improvement for infants under 18 months old of Dai minority in Luxi, China.

BACKGROUND: Child malnutrition and thiamine deficiency remain a matter of public concern in Dai children under 5 years old in Southwest areas of China. The aim of the present study was to understand the status and correlates of malnutrition and thiamine deficiency in Dai children under 18 months old in Yunnan, China, and to explore an effective intervention for improving their nutritional status and decreasing the prevalence of malnutrition and thiamine deficiency in Dai children. METHODS: Well-trained investigators completed a baseline evaluation survey, including questionnaire survey by maternal interviews, child physical measurements, lab examination of thiamine, and group discussions in a cross-sectional study. An intervention plan was constructed by a group consisting of the city governor, government officers, maternal and child health workers, community leaders, and villagers etc. A comprehensive community-based intervention was carried out for 352 children born after July 2001 and their mothers or caregivers in half of the baseline survey villages by the end of 2003. The intervention included participatory intervention, community nutrition education, child growth monitoring and distributing thiamine to new mothers just before or after delivery. RESULTS: The baseline evaluation survey in 2000 indicated that the prevalence of moderate and severe protein-energy malnutrition was 19.5% for underweight, 16.4% for stunting, and 6.7% for wasting, respectively. With increasing age, the prevalence increased, peaking at 12-15 months. The prevalence of underweight in girls was higher than in boys. A total of 10.5% of children suffered from thiamine deficiency, and 5.7% of the children were insufficient in thiamine supply. Low Kaup target (<25%) was significantly associated with lack of guidance by doctors, lack of nutrition knowledge, lack of knowledge of causes of malnutrition and local culture food taboos. The status of child nutrition has been improved significantly since the intervention measure implementation. The change of prevalence of underweight children aged 6-17 months prior to and after the intervention was significant: 20.5% before and 13.7% after the intervention in infants aged 6-11 months, and 39.0% before and 26.4% after the intervention in young children aged 12-17 months. Prevalence of girls was higher than that of boys. Some women began to eat vegetables and pork from the market, which were forbidden by the culture food taboos. There is no case report of child thiamine deficiency in project villages. CONCLUSION: The prevalence of moderate and severe protein-energy malnutrition is high in Dai infants and young children. However, based on the local situation, participatory community-based comprehensive nutrition intervention effectively reduces the prevalence of child malnutrition and thiamine deficiency. It is highlighted that population nutritional intervention can produce better results with participation at a community level.

[Neuromyelopathy in the population of Noir-marron of Saint-Laurent du Maroni in French Guiana]. / Neuromyélopathies dans la population de Noirs marrons de Saint-Laurent du Maroni en Guyane française.

The neurological observations have been reported at André Bouron Hospital of Saint-Laurent du Maroni and at General Hospital of Cayenne during a period of 5 years. All patients belonged to the "Noir Marron" ethnic group and lived in the area of Saint-Laurent. There were six women and four men, aged 15-35 years. Neurological symptoms were isolated or associated to other organ failure. Neurological manifestations included retrobulbar optic neuropathy, spastic paraparesis, sensitive ataxia and cerebellar ataxia, psychiatric symptoms were observed. Other organs affected were cardiovascular, digestive, cutaneous or endocrinologic (thyroid). Diet consist mainly in cassava. Thiamin deficiency has been observed several times. Improvement of neurological deficits following thiamin administration points towards Thiamin as an etiological factor. Ethnological specificity of Saint-Laurent area may explain that such neurological manifestation have not been observed in the rest of the department.

Thiamin intakes and erythrocyte thiamin levels in eleven-year-old children in the Western Cape.

Dietary intake of thiamin has been evaluated in a series of 615 eleven-year-old children in Western Cape Province, South Africa. Thiamin intakes, determined by 24-hour recall and local food composition tables, were highest in rural white children (boys 1.49 mg/day, girls 1.11 mg), followed by rural black (Xhosa) children (1.33, 1.15 mg), and lowest in rural (1.18, 1.11 mg) and urban coloured (Euro-African-Malay) subjects (1.11, 0.85 mg). The group means exceeded WHO recommended daily intakes except for urban coloured girls. Thiamin nutritional status was determined by automated microbiological assay of thiamin in erythrocytes in a subsample of 69 children. One urban coloured child was thiamin deficient. The highest mean value (69.4 micrograms/l) was found in rural coloured children, followed by their urban counterparts (64.8 micrograms/l) and black rural children (63.6 micrograms/l). Rural white children had the lowest mean value (60.3 micrograms/l). In general, thiamin stores in these children appear to be adequate.