18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

Patient, 1-month-old ALFP, born at term without intercurrences. In the first week of life, she sought medical care with maternal complaints of pallor, persistent crying and refusal to breastfeed, verified in a hemoglobin test of 4.5 g/dl, in addition to severe dysphagia in a contrast-enhanced test. In myelogram, presence of partial true megaloblastic transformation and expressive magaloblastic disposition. Evidenced in image exam global atrophy, both infra and supra tentorial, with signs of periventricular parenchymal hypodensity to the lateral ventricles. The diagnosis of Homocystinuria – Megaloblastic Anemia cblE came after a genetic panel with 2 verified in the MTRR gene (p.Gly548Alafs*2 and p.Lys382Glu), one known to be pathogenic and the other, until then, of uncertain clinical significance, interpreted as compound heterozygosity. The patient evolved with global delay in neuropsychomotor development. Initiate gained with vitamin B12, with hematimetric normalization, in addition to gains in cognitive and motor development.


Megaloblastic anemia-homocystinuria (cblE type) is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12) dependent pathway that converts homocysteine to methionine - catalyzed by methionine synthase (MTR). The clinic is heterogeneous and depends on the age of onset of symptoms, but neurological and hematological manifestations predominate. The confirmation of the diagnosis is through studies of the enzymatic activity and the complementary genetic analysis allows to distinguish the 3 CbIC groups. CbID and CbF. The treatment is based on the intramuscular administration of hydroxycobalamin. Other therapeutic adjuvants can be used, such as betaine, folic acid, carnitine and moderate protein restriction, with different results.

Comentários finais

The presentation of this report intends to address a rare inborn error of metabolism, but there is a simple treatment that installs early and later complications and major clinical ones. In addition, we present the description of a new mutation of unknown significance.

Referências (se houver)

Rosenblatt DS, Thomas IT, Watkins D, Cooper BA, Erbe RW. Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. Am J Med Genet. 1987 Feb;26(2):377-83. doi: 10.1002/ajmg.1320260216. PMID: 3812589.

Zavadakova, P., Fowler, B., Zeman, J., Suormala, T., Pristoupilova, K., Kozich, V. CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in 2 families. J. Inherit. Metab. Dis. 25: 461-476, 2002. Note: Erratum: J. Inherit. Metab. Dis. 26: 95 only, 2003.

Watkins, D., Rosenblatt, D. S. Genetic heterogeneity among patients with methylcobalamin deficiency. J. Clin. Invest. 81: 1690-1694, 1988.

Palavras Chave

Homocystinuria; Megaloblastic Anemia; MTRR gene; Vitamin B12

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Eu, Lethícia Nogueira Santos Barreto, autora responsável do relato, declaro que não há conflito de interesse da minha parte, bem como pelos co-autores envolvidos no trabalho.


Erros inatos do metabolismo


Universidade Estadual Paulista - UNESP - São Paulo - Brasil


Lethícia Nogueira Santos Barreto, Bruna Eugenia Gomes Felipe, Lucas Barbosa Napolitano de Moraes, Lara Cristina Antunes dos Santos, Maria Beatriz Bravin, Andrea Siqueira Campos Monti, Mirelle Tristão de Souza, Carolina Casarin Brosco, Gabriela de Castro Fim