Methylmalonic aciduria and homocystinuria type D protein, mitochondrial (MMADHC)

Methylmalonic aciduria and homocystinuria type D protein, mitochondrial (MMADHC) is a cytosolic and mitochondrial chaperone-like protein involved in vitamin B12 (cobalamin) metabolism[1][2][5]. It participates in the intracellular trafficking of cobalamin after its processing by MMACHC, directing it toward two essential cofactor forms—adenosylcobalamin (AdoCbl) for mitochondrial methylmalonyl-CoA mutase, and methylcobalamin (MeCbl) for cytosolic methionine synthase[1][2]. MMADHC does not possess catalytic activity itself but acts as a scaffold, with specific domains mediating delivery to either the mitochondrial or cytosolic pathways[1][3]. Mutations in MMADHC disrupt this trafficking, leading to combined or isolated methylmalonic aciduria with or without homocystinuria ("cblD" defect), a severe, rare inborn error of metabolism presenting with developmental delay, neurological, hematological, and ocular symptoms[2][3]. Currently, no drugs directly target MMADHC, and treatment is supportive, primarily via vitamin B12 administration in responsive patients.

Other names

Cobalamin trafficking protein CblDC2orf25CL25022HSPC161My011cblDHMADMACDMAHCDmethylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuriamethylmalonic aciduria and homocystinuria, cblD typemethylmalonic aciduria and homocystinuria type D protein, mitochondrial precursorMMAD_HUMAN

Not applicable (No drugs are known to directly target MMADHC; its role is as a scaffold/chaperone in biochemical pathways.)