Asunto(s)
Anemia Megaloblástica/genética , Diabetes Mellitus/genética , Pérdida Auditiva Sensorineural/genética , Deficiencia de Tiamina/congénito , Anemia Megaloblástica/historia , Niño , Diabetes Mellitus/historia , Femenino , Pérdida Auditiva Sensorineural/historia , Historia del Siglo XX , Humanos , Proteínas de Transporte de Membrana , Mutación , Deficiencia de Tiamina/genética , Deficiencia de Tiamina/historiaRESUMEN
Antecedentes. El síndrome de anemia megaloblástica sensible a la tiamina (TRMA, por sus siglas en inglés), también conocido como síndrome de Rogers, se caracteriza por presentar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Las alteraciones en el transporte de la tiamina hacia las células se deben a mutaciones homocigotas o heterocigotas compuestas en el gen SLC19A2. Presentación de un caso. Presentamos el caso de una niña que manifestaba sordera neurosensorial tratada con una prótesis auditiva, diabetes con necesidad de insulina y anemia macrocítica, tratada con tiamina (100 mg/día). El nivel de hemoglobina mejoró hasta alcanzar 12,1 g/dl después de aumentar la dosis terapéutica de tiamina hasta 200 mg/día. Conclusión. Se debe evaluar a los pacientes con TRMA para detectar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Se les debe dar seguimiento para determinar la respuesta de la enfermedad hematológica y de la diabetes después de la terapia con tiamina. La dosis terapéutica de tiamina puede aumentarse según la respuesta clínica. Debe proporcionarse asesoramiento genético.
Background. Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case presentation. We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. Conclusion. Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.
Asunto(s)
Humanos , Femenino , Lactante , Proteínas de Transporte de Membrana/genética , Deficiencia de Tiamina/congénito , Deficiencia de Tiamina/genética , Diabetes Mellitus/genética , Pérdida Auditiva Sensorineural/genética , Anemia Megaloblástica/genética , MutaciónRESUMEN
BACKGROUND: Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. CASE PRESENTATION: We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. CONCLUSION: Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.
ANTECENDENTES: El síndrome de anemia megaloblástica sensible a la tiamina (TRMA, por sus siglas en inglés), también conocido como síndrome de Rogers, se caracteriza por presentar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Las alteraciones en el transporte de la tiamina hacia las células se deben a mutaciones homocigotas o heterocigotas compuestas en el gen SLC19A2. PRESENTACIÓN DE UN CASO: Presentamos el caso de una niña que manifestaba sordera neurosensorial tratada con una prótesis auditiva, diabetes con necesidad de insulina y anemia macrocítica, tratada con tiamina (100 mg/día). El nivel de hemoglobina mejoró hasta alcanzar 12,1 g/dl después de aumentar la dosis terapéutica de tiamina hasta 200 mg/día. Conclusión. Se debe evaluar a los pacientes con TRMA para detectar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Se les debe dar seguimiento para determinar la respuesta de la enfermedad hematológica y de la diabetes después de la terapia con tiamina. La dosis terapéutica de tiamina puede aumentarse según la respuesta clínica. Debe proporcionarse asesoramiento genético.
Asunto(s)
Anemia Megaloblástica/genética , Diabetes Mellitus/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Transporte de Membrana/genética , Mutación , Deficiencia de Tiamina/congénito , Femenino , Humanos , Lactante , Deficiencia de Tiamina/genéticaRESUMEN
OBJECTIVE: To determine causative mutations and clinical status of 7 previously unreported kindreds with TRMA syndrome, (thiamine-responsive megaloblastic anemia, online Mendelian inheritance in man, no. 249270), a recessive disorder of thiamine transporter Slc19A2. STUDY DESIGN: Genomic DNA was purified from blood, and SLC19A2 mutations were characterized by sequencing polymerase chain reaction-amplified coding regions and intron-exon boundaries of all probands. Compound heterozygotes were further analyzed by sequencing parents, or cloning patient genomic DNA, to ascertain that mutations were in trans. RESULTS: We detected 9 novel SLC19A2 mutations. Of these, 5 were missense, 3 were nonsense, and 1 was insertion. Five patients from 4 kindreds were compound heterozygotes, a finding not reported previously for this disorder, which has mostly been found in consanguineous kindreds. CONCLUSION: SLC19A2 mutation sites in TRMA are heterogeneous; with no regional "hot spots." TRMA can be caused by heterozygous compound mutations; in these cases, the disorder is found in outbred populations. To the extent that heterozygous patients were ascertained at older ages, a plausible explanation is that if one or more allele(s) is not null, partial function might be preserved. Phenotypic variability may lead to underdiagnosis or diagnostic delay, as the average time between the onset of symptoms and diagnosis was 8 years in this cohort.
Asunto(s)
Anemia Megaloblástica/genética , Heterocigoto , Proteínas de Transporte de Membrana/genética , Mutación/genética , Tiamina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Adulto , Anemia Megaloblástica/complicaciones , Anemia Megaloblástica/tratamiento farmacológico , Niño , Preescolar , Estudios de Cohortes , Sordera/etiología , Diabetes Mellitus/etiología , Femenino , Humanos , Lactante , Masculino , FenotipoRESUMEN
Thiamine-responsive megaloblastic anemia is a rare autosomal recessive disorder whose main symptoms are anemia, diabetes mellitus, and sensorineural deafness. We describe a 20-year follow-up of 2 previously reported patients and of 1 patient diagnosed before onset of symptoms and treated with thiamine since the first sign of disease.
Asunto(s)
Anemia Megaloblástica/tratamiento farmacológico , Tiamina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Anemia Megaloblástica/genética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Femenino , Estudios de Seguimiento , Pérdida Auditiva Sensorineural/genética , Humanos , Adulto JovenAsunto(s)
Anemia Macrocítica/genética , Anemia Megaloblástica/genética , Homocistinuria/genética , Malonatos/orina , Ácido Metilmalónico/orina , Mutación , Deficiencia de Vitamina B 12/genética , Vitamina B 12/uso terapéutico , Anemia Megaloblástica/tratamiento farmacológico , Fibroblastos/metabolismo , Homocistinuria/tratamiento farmacológico , Humanos , Recién Nacido , Masculino , Vitamina B 12/farmacocinética , Deficiencia de Vitamina B 12/tratamiento farmacológicoRESUMEN
Three brothers with diabetes mellitus, thiamine-responsive megaloblastic anemia, and sensorineural deafness are reported. Two had, in addition, congenital septal defects. The activities of thiamine-dependent enzymes were determined in one patient, revealing low alpha-ketoglutarate dehydrogenase activity, which could have caused a sideroblastic anemia with secondary megaloblastic changes. The anemia was thiamine dependent. The cause of the diabetes mellitus was not known, but it was not type 1.