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

A method of treating a 4-hydroxyphenylpyruvate dioxygenase-like (HPDL)-related disease or disorder in a subject in need thereof, comprising:

• a. detecting the presence of one or more mutations in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis in a biological sample obtained from the subject, wherein the one or more mutations result in reduced or abolished activity and/or expression of the protein(s) produced by said gene(s);
• and
• b. (i) when the one or more mutations are present in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis, administering to the subject a therapeutically effective amount of 4-hydroxymandelic acid (4-HMA), or a metabolite, pharmaceutically acceptable salt, prodrug, solvate, hydrate, or combinations thereof;
• or (ii) when the one or more mutations are absent in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis, not administering 4-hydroxymandelic acid (4-HMA), or a metabolite, pharmaceutically acceptable salt, prodrug, solvate, hydrate, or combinations thereof, to the subject.

A method of treating a 4-hydroxyphenylpyruvate dioxygenase-like (HPDL)-related disease or disorder in a subject in need thereof, comprising

• a. detecting the presence of one or more mutations in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis in a biological sample obtained from the subject, wherein the one or more mutations result in reduced or abolished activity and/or expression of the protein(s) produced by said gene(s);
• and
• b. (i) when the one or more mutations are present in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis, administering to the subject a therapeutically effective amount of an activator of HPDL;
• or (ii) when the one or more mutations are absent in the HPDL gene and/or additional gene(s) involved in CoQ10 headgroup synthesis, not administering the activator of HPDL to the subject.