RESUMEN
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/ ).
Asunto(s)
Anemia Megaloblástica/tratamiento farmacológico , Anemia Megaloblástica/genética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/genética , Farmacogenética , Deficiencia de Tiamina/congénito , Tiamina/uso terapéutico , Alelos , Preescolar , Estudios de Cohortes , Femenino , Pruebas Genéticas , Genotipo , Humanos , Lactante , Masculino , Proteínas de Transporte de Membrana/genética , Mutación , Fenotipo , Encuestas y Cuestionarios , Deficiencia de Tiamina/tratamiento farmacológico , Deficiencia de Tiamina/genéticaRESUMEN
Neonatal adrenal hematoma is a rare finding that can be discovered incidentally or presents with various symptoms. However, urinary tract infection (UTI) has not been reported in association with this condition. We report on a 4-week old child with massive unilateral adrenal hematoma discovered incidentally during a routine abdominal ultrasound scan for UTI. The mass resolved spontaneously after several months with no complications. The diagnosis and management of infantile suprarenal mass and the possible link between this child's UTI and the adrenal hematoma are discussed.