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Recessive spastic paraparesis associated with complex I deficiency due to MTHFR mutations
  1. Deborah Bathgate1,
  2. Patrick Yu-Wai-Man2,
  3. Brian Webb3,
  4. Robert W Taylor2,
  5. Brian Fowler4,
  6. Patrick F Chinnery2
  1. 1Department of Neurology, James Cook University Hospital, Middlesbrough, UK
  2. 2Mitochondrial Research Group, Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK
  3. 3Department of Biochemistry, James Cook University Hospital, Middlesbrough, UK
  4. 4University Children's Hospital (UKBB), Basel, Switzerland
  1. Correspondence to Professor P F Chinnery, Institute of Human Genetics, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK; p.f.chinnery{at}ncl.ac.uk

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5,10-Methylenetetrahydrofolate reductase (MTHFR, EC.1.5.1.20) catalyses the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This serves as a methyl donor for homocysteine re-methylation to methionine, which is essential for DNA and protein methylation, neurotransmitter and phospholipid synthesis. Homocystinuria due to MTHFR deficiency usually presents in childhood with developmental delay, psychiatric features, and an encephalopathy with low or normal plasma methionine.1 Onset in late childhood or early adult life is rare.1 Here we describe MTHFR deficiency presenting in two adult siblings with slowly progressive spastic paraparesis.

Case report

A young adult of Pakistani origin presented with a 2 year history of walking difficulty due to a spastic paraparesis. Brain and spinal cord MR imaging was normal, as were electromyography, nerve conduction studies, and visual evoked potentials. Routine haematological and biochemical blood tests were normal, as were levels of vitamin B12, folate, very long chain fatty acids, hexosaminidase, copper, and HTLV1 antibodies. The parents were first cousins, leading to a clinical diagnosis of autosomal recessive hereditary spastic paraparesis (HSP).

Five years later the patient presented acutely with a behavioural disturbance, urinary and faecal …

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