Methods and compositions for treating 4-hydroxyphenylpyruvate dioxygenase-like (hpdl)-related diseases or disorders

Various methods and compositions of treating 4-hydroxyphenylpyruvate dioxygenase-like (HPDL)-r elated diseases or disorders are presented herein. Also presented herein are methods of increasing CoQlO biosynthesis, and methods of determining whether a subject will benefit from a CoQlO or CoQlO alternative treatment. Also presented herein are pharmaceutical compositions and dosage forms comprising 4-hydroxymandelic acid (4-HMA), and/or its metabolites. Further presented herein are compounds that inhibit 4-hydroxyphenylpyruvate dioxygenase-like (HPDL). Further presented herein are methods of identifying and/or assessing modulators of HPDL. Yet further presented herein are example methods and systems for isotopic labelling in cells by metabolizing cells in the presence of gaseous isotopic tracer.