Treatment for rare form of complicated HSP

Posted - June 2014 in Research Highlights

Betaine successful in lowering cysteine

IMPORTANCE

Hereditary spastic paraplegia is a highly heterogeneous group of neurogenetic disorders with pure and complicated clinical phenotypes. No treatment is available for these disorders.

We identified 2 unrelated families, each with 2 siblings with severe methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting a complicated form of adult-onset hereditary spastic paraparesis partially responsive to betaine therapy.

 OBSERVATIONS

Both pairs of siblings presented with a similar combination of progressive spastic paraparesis and polyneuropathy, variably associated with behavioral changes, cognitive impairment, psychosis, seizures, and leukoencephalopathy, beginning between the ages of 29 and 50 years. By the time of diagnosis a decade later, 3 patients were ambulatory and 1 was bedridden.

Investigations have revealed severe hyperhomocysteinemia and hypomethioninemia, reduced fibroblast MTHFR enzymatic activity (18%-52% of control participants), and 3 novel pathogenic MTHFR mutations, 2 as compound heterozygotes in one family and 1 as a homozygous mutation in the other family. Treatment with betaine produced a rapid decline of homocysteine by 50% to 70% in all 4 patients and, over 9 to 15 years, improved the conditions of the 3 ambulatory patients.

CONCLUSIONS AND RELEVANCE

Although severe MTHFR deficiency is a rare cause of complicated spasticparaparesis in adults, it should be considered in select patients because of the potential therapeutic benefit of betaine supplementation.

 

SOURCE: JAMA Neurol. 2014 May 5.doi: 10.1001/jamaneurol.2014.116. [Epub ahead of print] PMID: 24797679 (PubMed – as supplied by publisher)

Severe Methylenetetrahydrofolate Reductase Deficiency: Clinical Clues to a Potentially Treatable Cause of Adult-Onset Hereditary Spastic Paraplegia.

Lossos A1, Teltsh O2, Milman T3, Meiner V4, Rozen R5, Leclerc D5, Schwahn BC5, Karp N5, Rosenblatt DS6, Watkins D7, Shaag A4, Korman SH4, Heyman SN8, Gal A1, Newman JP1, Steiner-Birmanns B9, Abramsky O1, Kohn Y10.

  • 1Center for Human Neurogenetics, Department of Neurology and Agnes Ginges, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
  • 2Hebrew University-Hadassah School of Medicine, Jerusalem, Israel3National Institute for Biotechnology in the Negev, Ben Gurion University, Beer Sheva, Israel.
  • 3Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
  • 4Department of Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel5Department of Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
  • 5Department of Human Genetics, McGill University, Montreal, Quebec, Canada7Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
  • 6Department of Human Genetics, McGill University, Montreal, Quebec, Canada7Department of Pediatrics, McGill University, Montreal, Quebec, Canada8Department of Medicine, McGill University, Montreal, Quebec, Canada9Department of Biology, McGill University, M.
  • 7Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • 8Department of Internal Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
  • 9Department of Neurology, Shaare Zedek Medical Center, Jerusalem, Israel.
  • 10Hebrew University-Hadassah School of Medicine, Jerusalem, Israel12Department of Child and Adolescent Psychiatry, Jerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem, Israel.

 

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