Korsakoff syndrome (KS) is a disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation. This neurological disorder is caused by a deficiency of thiamine (vitamin B1) in the brain, and it is typically associated with and exacerbated by the prolonged, excessive ingestion of alcohol. Korsakoff syndrome is often accompanied by Wernicke encephalopathy; this combination is called Wernicke–Korsakoff syndrome.Korsakoff syndrome is named after Sergei Korsakoff, the Russian neuropsychiatrist who described it during the late 19th century. Signs and symptoms
There are seven major symptoms of Korsakoff syndrome, an amnestic-confabulatory syndrome:
anterograde amnesia, memory loss for events after the onset of the syndrome
retrograde amnesia, memory loss extends back for some time before the onset of the syndrome
amnesia of fixation, also known as fixation amnesia (loss of immediate memory, a person being unable to remember events of the past few minutes)
confabulation, that is, invented memories which are then taken as true, due to gaps in memory, with such gaps sometimes associated with blackouts
minimal content in conversation
lack of insight
apathy – interest in things is quickly lost, and there is an indifference to changeBenon R. and LeHuché R. (1920) described the characteristic signs of Korsakoff syndrome with some additional features including: confabulation (false memories), fixation amnesia, paragnosia or false recognition of places, mental excitation, and euphoria.Thiamine is essential for the decarboxylation of pyruvate, and deficiency during this metabolic process is thought to cause damage to the medial thalamus and mammillary bodies of the posterior hypothalamus, as well as generalized cerebral atrophy.
There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population.There are an estimated 3,600 MLD births per year, with 1,900 alive in the US, 3,100 in Europe, and 49,000 alive worldwide with MLD.MLD is considered a rare disease in the US and other countries. Research
Bone marrow and stem cell transplant therapies
Several trials are underway to continue to improve the effectiveness and reduce the risks of bone marrow and stem cell transplants. Gene therapy
(current as of April 2021)
Two different approaches to gene therapy are currently being researched for MLD. Gene therapy with an autologous stem cell transplant – Italian researchers at the San Raffaele Telethon Institute tested a novel approach combining gene therapy with an autologous stem cell transplant.Gene therapy for late infantile and early juvenile patients was approved by the European Commission in December 2020 after receiving a favorable European Medicines Agency CHMP review in October 2020. The product is being marketed in the EU as Libmeldy. Libmeldy is a gene therapy medicinal product, for which CD34+ haematopoietic stem and progenitor cells are collected either from the patients own bone marrow or mobilised peripheral blood.