ABSTRACT
AIMS/HYPOTHESIS: Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes. METHODS: We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. RESULTS: We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes onset was 10 months (IQR 5-27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine (p = 0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day. CONCLUSIONS/INTERPRETATION: In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent. DATA AVAILABILITY: SLC19A2 mutation details have been deposited in the Decipher database ( https://decipher.sanger.ac.uk/ ).
Subject(s)
Anemia, Megaloblastic/drug therapy , Anemia, Megaloblastic/genetics , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sensorineural/genetics , Pharmacogenetics , Thiamine Deficiency/congenital , Thiamine/therapeutic use , Alleles , Child, Preschool , Cohort Studies , Female , Genetic Testing , Genotype , Humans , Infant , Male , Membrane Transport Proteins/genetics , Mutation , Phenotype , Surveys and Questionnaires , Thiamine Deficiency/drug therapy , Thiamine Deficiency/geneticsABSTRACT
BACKGROUND: Catheter-associated Candida bloodstream infections are a common and serious problem in the neonatal intensive care unit (NICU). Several prophylactic regimens have been developed including oral administration of nonabsorbable antifungals and intravenous infusions. No reports to date have employed a topical regimen. PURPOSE: To evaluate the effectiveness of topical nystatin cream in preventing catheter-associated Candida sepsis. METHODS: A retrospective descriptive design was used to determine the incidence of Candida sepsis in extremely low-birth weight (ELBW, <1000 g at birth) infants who were treated with topical nystatin cream for Candida bloodstream infection prophylaxis between January 1, 2000, and December 31, 2010. The electronic medical records of study infants were reviewed to establish the incidence of Candida sepsis. RESULTS: A total of 464 ELBW infants were admitted to the NICU during the study period. Three infants (0.65%) developed Candida sepsis. IMPLICATIONS FOR PRACTICE: These data demonstrate that a topical nystatin cream protocol is associated with a very low rate of Candida sepsis in ELBW infants with central catheters. The use of this protocol may contribute to a decrease in the morbidity and mortality rate associated with catheter-associated Candida infections in ELBW infants. IMPLICATIONS FOR RESEARCH: Before generalizations can be made as to the safety and efficacy of this protocol as compared to enteral and parenteral prophylactic treatments and in other institutions, large multicenter randomized controlled trials are required.
