RESUMO
OBJECTIVES: Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. CASE PRESENTATION: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Anemia Macrocítica , Deficiência de Vitamina B 12 , Recém-Nascido , Humanos , Vitamina B 12/uso terapêutico , Transcobalaminas/genética , Estudos Retrospectivos , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/genética , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Diagnóstico PrecoceRESUMO
OBJECTIVE: To evaluate the clinical outcomes at age 1.5 ± 0.5 years of infants with vitamin B12 deficiency identified by newborn screening (NBS). STUDY DESIGN: Prospective multicenter observational study on health outcomes of 31 infants with vitamin B12 deficiency identified by NBS. Neurodevelopment was assessed by the Denver Developmental Screening Test. RESULTS: In 285â862 newborns screened between 2016 and 2019, the estimated birth prevalence of vitamin B12 deficiency was 26 in 100â000 newborns, with high seasonal variations (lowest in summer: 8 in 100â000). Infants participating in the outcome study (N = 31) were supplemented with vitamin B12 for a median (range) of 5.9 (1.1-16.2) months. All achieved age-appropriate test results in Denver Developmental Screening Test at age 15 (11-23) months and did not present with symptoms characteristic for vitamin B12 deficiency. Most (81%, n = 25) mothers of affected newborns had a hitherto undiagnosed (functional) vitamin B12 deficiency, and, subsequently, received specific therapy. CONCLUSIONS: Neonatal vitamin B12 deficiency can be screened by NBS, preventing the manifestation of irreversible neurologic symptoms and the recurrence of vitamin B12 deficiency in future pregnancies through adequate treatment of affected newborns and their mothers. The high frequency of mothers with migrant background having a newborn with vitamin B12 deficiency highlights the need for improved prenatal care.
Assuntos
Deficiência de Vitamina B 12 , Vitamina B 12 , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Triagem Neonatal , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Estudos Prospectivos , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/epidemiologia , VitaminasRESUMO
Se presenta el caso de un paciente adulto mayor con antecedente de haber presentado úlcera gástrica hace 40 años, cuyos familiares observaron desde hace dos meses cambios en el comportamiento, los cuales incluyeron progresivamente desorientación, agitación psicomotriz, negativismo, delirio de persecución, lo que motivó ser traído al servicio de emergencia. Así mismo presentó palidez marcada y equimosis múltiple, por lo cual fue admitido posteriormente en nuestro servicio y diagnosticado de demencia reversible por anemia perniciosa. También se le detectó pancitopenia y cambios neurológicos. El paciente respondió favorablemente a la administración de vitamina B12.
This is the case of an elderly patient with a 40-year history of stomach ulcer, whose relatives perceived behavioral changes for the last two months. Those changes progressively included disorientation, psychomotor agitation, negativism and delirium of persecution, which caused him to be brought to the emergency room. He also showed marked pallor and multiple ecchymosis, due to which he was hospitalized in our service and diagnosed with reversible dementia caused by pernicious anemia. Pancytopenia and neurological changes were also found. The patient responded favorably to the administration of vitamin B12.
RESUMO
Embora o quadro clássico de mielopatia por deficiência de vitaminaB12 seja a degeneração subaguda combinada da medula, a manifestaçãoclínica pode ser variável. Homem branco de 36 anos de idade com hipotireoidismo e vitiligo apresentou dormência nas mãos de início súbito. Exame físico: sinal de Lhermitte e hipoestesia nas palmas. Evidenciada alteração de sinal na ressonância magnética (RM) da medula cervical. Foram evidenciados nível sérico de vitamina B12 de 150 pg/mL, gastrite atrófica e hemograma normal. Paciente foi tratado com reposição intramuscular de vitamina B12. Após seis meses, houve remissão completa dos sintomas com normalização do exame de imagem em um ano. O presente caso ilustra discreta alteração clínica e lesão extensa na RM (dissociação entre a clínica e o exame de imagem) na deficiência de B12. A melhora dos sintomas precedeu a resolução da alteração no exame de imagem, no presente caso.
Although the classic manifestation of myelopathy due to vitamin B12deficiency is a subacute combined degeneration of the spinal cord, the clinical manifestation may be varied. A 36-year-old white man with hypothyroidism and vitiligo presented sudden onset of numbness in hands. Physical examination: Lhermitte's sign and hypoesthesia in palms. Signal change on magnetic resonance image (MRI) of the cervical spinal cord was evidenced. Serum vitamin B12 of 150 pg/mL, gastric atrophy and normal hemogram were shown. The patient was treated with intramuscular vitamin B12 replacement. After six months there was complete remission of the symptoms, and within one year the MRI was normal. This case illustrates mild clinical signs and extensive changes on MRI (dissociation between clinic and image) in B12 deficiency. Resolution of MRI was observed after the clinical signs, in the present case.