Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease)

Journal of Inherited Metabolic Disease
Brian FowlerJ Lindemans

Abstract

This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, megaloblastic anaemia, increased plasma free homocystine (> 20 mumol/L), low plasma methionine (< 10 mumol/L) and increased excretion of formiminoglutamate. On high-dose folic acid, biochemical abnormalities such as formiminoglutamate excretion and homocystinuria nearly normalized, but clinical and haematological abnormalities remained. On replacement of folate with methylcobalamin, alertness, motor function, speech and the electroencephalogram improved, biochemical features were similar, but the mean corpuscular volume increased. The best control was observed on a combination of folate and methylcobalamin. At 17 years of age she remains severely mentally retarded. In cultured fibroblasts methionine synthesis was reduced (0.03 nmol/mg/per 16 h, controls 2.4-6.9); methionine synthase activity was normal under high reducing conditions but decreased on limiting the reducing agent, dithiothreitol, to 5 mmol/L (18% of to...Continue Reading

References

Nov 1, 1978·The Journal of Clinical Investigation·I MellmanL E Rosenberg
Dec 1, 1978·Clinica Chimica Acta; International Journal of Clinical Chemistry·M DuranH A Veder
Mar 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R V Banerjee, R G Matthews
Nov 1, 1989·American Journal of Medical Genetics·D Watkins, D S Rosenblatt
Dec 1, 1989·Blood Reviews·I ChanarinJ Perry
Jul 1, 1985·The Journal of Clinical Investigation·G R Boss
Jun 30, 1988·The New England Journal of Medicine·R CarmelD S Rosenblatt
Feb 1, 1987·American Journal of Medical Genetics·D S RosenblattR W Erbe
Aug 20, 1974·Clinica Chimica Acta; International Journal of Clinical Chemistry·A NiederwieserK Baerlocher
Apr 1, 1970·Journal of Clinical Pathology·B B AndersonC E Fulford-Jones
Jan 24, 1983·Clinica Chimica Acta; International Journal of Clinical Chemistry·A H GijzenC E Voogd
Jul 15, 1983·Clinica Chimica Acta; International Journal of Clinical Chemistry·J van KapelJ Abels
Mar 1, 1993·Metabolism: Clinical and Experimental·R C ChuC A Hall
Jun 1, 1958·The Journal of Clinical Investigation·H TABOR, L WYNGARDEN

❮ Previous
Next ❯

Citations

Jul 14, 2001·Critical Reviews in Clinical Laboratory Sciences·J G Donnelly
Mar 13, 2015·Journal of Inherited Metabolic Disease·Martina HuemerHenk J Blom
Dec 23, 2006·Journal of Inherited Metabolic Disease·P J Lee, A Briddon
Apr 8, 2006·Journal of Inherited Metabolic Disease·R CastroI Tavares de Almeida
Mar 21, 2007·Molecular Genetics and Metabolism·C Lee ElmoreRowena G Matthews
Mar 12, 2010·Molecular Genetics and Metabolism·D S FroeseR A Gravel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.