Neurological
Vitamin-Responsive Neurogenic Disorders: Role in Diseases, Tests, and Future Directions
Vitamin-responsive hereditary diseases are a rare set of disorders that can be underdiagnosed in adults. In a review article recently published in JAMA Neurology, researchers outlined clinical situations when diagnostic tests for vitamin-responsive hereditary diseases should be performed and when vitamins should be given for optimal disease outcomes.
According to the researchers of the study, the pathophysiology of vitamin-responsive diseases can be divided into 4 groups: patients with impaired cofactor synthesis from vitamins; impaired transport of vitamins; enzymatic defect requiring a vitamin-derived cofactor; and a secondary vitamin defect caused by abnormalities unrelated to a genetic defect involved in vitamin metabolism.
The tools available to support the diagnostic process of vitamin-responsive hereditary diseases include clinically oriented gene panels, whole exome sequencing, and whole genome sequencing. In many different clinical situations, a valid diagnostic approach involves a first-line or parallel biochemical strategy.
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The first-line biochemical or parallel diagnostic approach may be largely appropriate, considering that some clinical situations do not always indicate a genetic causative factor in advance. This leads to several tests being carried out to determine the causative factor.
According to the study researchers, genetic tests have their limits in vitamin-responsive diseases. For example, the time it takes to obtain genetic test results can lead to delays in vitamin administration in situations where immediate therapy is imperative. Genetic tests may also not be able to recognize or interpret different variants. After all, genetic testing is not readily available in certain regions, while vitamins are abundant and readily available worldwide.
Certain conditions for which vitamin administration may be appropriate in connection with hereditary diseases responsive to vitamin include muscle and nervous diseases, Hartnup disorder, biotinidase deficiency, and parkinsonism.
The field of research into vitamin-responsive hereditary diseases is expanding rapidly. Given their evolving nature, it is likely that some hereditary, vitamin-responsive diseases previously reported only in children are now documented in adults.
Therefore, the researchers in this review concluded that a study of vitamin supplementation “is needed in patients with phenotypes similar to or close to a known vitamin-responsive genetic disorder, even if classical biochemical and genetic studies (including Ganz-Exome and Ganz -Genome sequencing) “) have negative results.”
reference
Mandia D, Shor N, Benoist JF, Nadjar Y. Vitamin-Responsive Neurogenetic Disorders in Adolescence and Adulthood: A Review. JAMA Neurol. 2021; 78 (4): 483-490. doi: 10.1001 / jamaneurol.2020.4911