A rare inborn error of intracellular processing of cobalamin presenting with microcephalus and megaloblastic anemia:: A report of 3 children

被引:9
作者
Muller, P.
Horneff, G.
Hennermann, J. B.
机构
[1] HELIOS Krankenhaus Leisnig, Abt Kinder & Jugendmed, D-04703 Leisnig, Germany
[2] Asklepios Klin St Augustin, Zentrum Allgemeine Padiat & Neonatol, St Augustin, Germany
[3] Univ Med Berlin, Otto Heubner Centrum Kinder & Jugendmed, Berlin, Germany
来源
KLINISCHE PADIATRIE | 2007年 / 219卷 / 06期
关键词
cobalamine defect type E; homocysteine; megaloblastic anemia; microcephalus;
D O I
10.1055/s-2007-973067
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Introduction: Defects of methionine synthase or methionine synthase reductase result in an impaired remethylation of homocysteine to methionine. Patients present with megaloblastic anemia, failure to thrive and various neurological manifestations including mental retardation, cerebral atrophy, muscular hypotonia or hypertonia, ataxia, seizures, nystagmus and visual disturbances. Patients: We report on three children (two girls, one boy), aged 3.5-7.5 years, who presented with severe megaloblastic anemia, microcephalus and partly nystagmus (2/3) due to a rare inborn error of remethylation. Results: Methionine synthase reductase deficiency, cblE type of homocystinuria (OMIM 236270), is a rare autosomal recessive inherited disorder described only in 14 patients worldwide. Metabolic hallmarks of the disease are hyperhomocysteinemia (median 98 mu mol/l, normal range < 15) without methylmalonic aciduria but often hypomethioninemia. The patients described here were diagnosed at ages of 2-18 months. The importance of an early recognition of this possibly underdiagnosed congenital disease is stressed. Treatment consisted of the application of hydroxocobalamine (1-2mg weekly, i.m.), betaine (100-200mg/kg daily, p.o.), folate (5-10mg daily, p.o.) and intensive physical therapy. Conclusion: Defects of intracellular processing of cobalamine must be considered in all patients with neurological symptoms in combination with megaloblastic anemia. Measurements of homocysteine and methionine in plasma as well as methylmalonic acid in urine is required for confirming the diagnosis. Early treatment improves the outcome, although mental disability may not be prevented. Treatment has a positive impact on megaloblastic anemia but only slight effect on hype rho mocysteinemia. The long-term cardiovascular risk of hyperhomocysteinemia in cblE deficient patients is not known yet.
引用
收藏
页码:361 / 367
页数:7
相关论文
共 32 条
  • [1] SERUM BETAINE, N,N-DIMETHYLGLYCINE AND N-METHYLGLYCINE LEVELS IN PATIENTS WITH COBALAMIN AND FOLATE-DEFICIENCY AND RELATED INBORN-ERRORS OF METABOLISM
    ALLEN, RH
    STABLER, SP
    LINDENBAUM, J
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 1993, 42 (11): : 1448 - 1460
  • [2] BALKENHOL ND, 2003, MONATSSCHR KINDERH S, V1, P151
  • [3] TNFα contributes to the death of NGF-dependent neurons during development
    Barker, V
    Middleton, G
    Davey, F
    Davies, AM
    [J]. NATURE NEUROSCIENCE, 2001, 4 (12) : 1194 - 1198
  • [4] Myelinolytic lesions in spinal cord of cobalamin-deficient rats are TNF-α-mediated
    Buccellato, FR
    Miloso, M
    Braga, M
    Nicolini, G
    Morabito, A
    Pravettoni, G
    Tredici, G
    Scalabrino, G
    [J]. FASEB JOURNAL, 1999, 13 (02) : 297 - 304
  • [5] Remethylation defects: guidelines for clinical diagnosis and treatment
    de Baulny, HO
    Gerard, M
    Saudubray, JM
    Zittoun, J
    [J]. EUROPEAN JOURNAL OF PEDIATRICS, 1998, 157 (Suppl 2) : S77 - S83
  • [6] Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria
    Dobson, CM
    Wai, T
    Leclerc, D
    Kadir, H
    Narang, M
    Lerner-Ellis, JP
    Hudson, TJ
    Rosenblatt, DS
    Gravel, RA
    [J]. HUMAN MOLECULAR GENETICS, 2002, 11 (26) : 3361 - 3369
  • [7] Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease)
    Fowler, B
    Schutgens, RBH
    Rosenblatt, DS
    Smit, GPA
    Lindemans, J
    [J]. JOURNAL OF INHERITED METABOLIC DISEASE, 1997, 20 (06) : 731 - 741
  • [8] Defects in human methionine synthase in cblG patients
    Gulati, S
    Baker, P
    Li, YN
    Fowler, B
    Kruger, W
    Brody, LC
    Banerjee, R
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 (12) : 1859 - 1865
  • [9] PLASMA-CONCENTRATIONS OF HOMOCYSTEINE AND OTHER AMINOTHIOL COMPOUNDS ARE RELATED TO FOOD-INTAKE IN HEALTHY-HUMAN SUBJECTS
    GUTTORMSEN, AB
    SCHNEEDE, J
    FISKERSTRAND, T
    UELAND, PM
    REFSUM, HM
    [J]. JOURNAL OF NUTRITION, 1994, 124 (10) : 1934 - 1941
  • [10] HALLAM LJ, 1987, BLOOD, V69, P1128