Department of Neurology, Shanghai Children's Hospital, Yuan Fang, Chen Yucai
In 1983, the Odens' six-year-old son Lorenzo suddenly and brutally threw things on the ground during class, this child born in a family of financial scientists was lively and cheerful, intelligent and polite from an early age, this move attracted the attention of the teacher, and in the following months, the parents found that their son's temper suddenly became grumpy, walking unsteadily, his memory deteriorated, and the sound of the sound became louder and louder when listening to music. On the day of the medical examination, doctors found extensive, symmetrical white matter lesions in his skull imaging; levels of very long-chain fatty acids (VLCFAs) in the blood were markedly elevated, and Lorenzo was diagnosed with adrenal leukodystrophy, a rare disease predicted to survive only two years.
Adrenoleukodystrophy (ALD) is a rare disease of abnormal lipid metabolism caused by abnormal peroxisome function caused by mutations in the ABCD1 gene on the X chromosome (Xq28) (adenosine triphosphate-binding cassette D1), with an incidence of 1/21 000 to 1/15 500. Clinical manifestations are progressive demyelinating of the white matter of the brain and adrenal insufficiency. There are two ways of heredity of the disease: (1) autostained inheritance, neonatal onset, relatively rare; (2) X-linked recessive inheritance, childhood or youth onset, mainly based on auditory and visual function impairment, intelligence loss, behavioral abnormalities, movement disorders as the main manifestations, poor prognosis.
Lorenzo became ill because he inherited the ABCD1 mutation gene carried in his mother's X chromosome, and his nervous system was invaded by VLCFA: the myelin sheath became inflamed and disappeared, and in just a few months he lost control of his limbs, swallowing, and language function, and had frequent, uncontrollable epilepsy. The Audens began to study ALD, and the parents, in order to save their children, began to devote themselves to the obscure study of biochemistry in order to solve the mystery of the metabolism of very long-chain fatty acids. 28 months after his diagnosis, "Lorenzo's oil", a mixture of trioleate glyceryl and trichocionate, was born to treat the rare disease that his son Lorenzo suffered from. After treatment, although Lorenzo VLCFA returned to normal, the neurological damage that had occurred could not be repaired, Lorenzo's physical condition did not improve significantly, and he died at the age of 30. This is the story of the famous Lorenzo's oil, in those years when medicine was not developed enough, Lorenzo's oil seemed to be the straw for early diagnosis of children's life, for those children who were found early and actively treated can indeed improve the survival rate and quality of life to a certain extent.
Although "Lorenzo's oil" reduces the synthesis of VLCFA in patients with ALD, there is controversy in clinical applications, and for patients with ALD, the current treatment of choice is allogeneic stem cell transplantation. Since 2017, the Department of Neurology of Shanghai Children's Hospital has cooperated with the Department of Hematology to carry out allogeneic hematopoietic stem cell transplantation for children with ALD, which not only prolongs the survival period of children with early ALD, but also greatly improves and improves their quality of life. It is the most effective treatment for the treatment of early ALD at this stage. Up to now, the Department of Neurology and the Department of Hematology of Shanghai Children's Hospital have successfully carried out hematopoietic stem cell transplantation treatment for 2 children with peroxisome disease, and the prognosis of the children is good.
Expert introduction
Yuan Fang
Yuan Fang, attending physician of the Department of Neurology, Shanghai Children's Hospital, master's degree from Shanghai Jiao Tong University School of Medicine, specializes in epilepsy, neuroimmune-related diseases, tic disorders, etc., and published SCI2 articles.
Chen Yucai
Deputy Director of neurology. Adjunct Associate Professor, OSF Children's Hospital, USA. He studied under Professor Wang Meixian, Professor Murong Shenxing, Professor Wu Xiru, and Professor William Davis Parker. Winner of the National Outstanding Doctoral Dissertation. The total SCI impact factor of published articles exceeds 20 points, and the total number of citations exceeds 400 times. CACNA1H, a susceptibility gene for childhood absence epilepsy, was discovered and its function was systematically studied. He is a member of the International Children's Multiple Sclerosis Group. He was a member of the Fujian Pediatrics Branch of the Chinese Medical Association and the deputy leader of the Pediatric Neurology Group of Fujian Province. He is a member of the American Neurology Association and a member of the Research Committee of the University of Illinois at Chicago.
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