TY - JOUR
T1 - Observations regarding retinopathy in mitochondrial trifunctional protein deficiencies
AU - Fletcher, Autumn L.
AU - Pennesi, Mark E.
AU - Harding, Cary O.
AU - Weleber, Richard G.
AU - Gillingham, Melanie B.
N1 - Funding Information:
We would like to thank Dr. Arnold Strauss for kindly providing the illustration of TFP in Fig. 1 b. Supported by the National Institutes of Health grant NIH T32GM08796 , NIDDK F32DK065400 (MBG), the Doernbecher Children’s Hospital Foundation , and the Oregon Clinical and Translational Research Institute (OCTRI), grant numbers ULI RR024140 and TL1 RR024159 from the National Center for Research Resources (NCRR) , and the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research.
PY - 2012/5
Y1 - 2012/5
N2 - Although the retina is thought to primarily rely on glucose for fuel, inherited deficiency of one or more activities of mitochondrial trifunctional protein results in a pigmentary retinopathy leading to vision loss. Many other enzymatic deficiencies in fatty acid oxidation pathways have been described, none of which results in retinal complications. The etiology of retinopathy among patients with defects in trifunctional protein is unknown. Trifunctional protein is a heteroctomer; two genes encode the alpha and beta subunits of TFP respectively, HADHA and HADHB. A common mutation in HADHA, c.1528. G > C, leads to a single amino acid substitution, p. Glu474Gln, and impairs primarily long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity leading to LCHAD deficiency (LCHADD). Other mutations in HADHA or HADHB often lead to significant reduction in all three enzymatic activities and result in trifunctional protein deficiency (TFPD). Despite many similarities in clinical presentation and phenotype, there is growing evidence that they can result in different chronic complications. This review will outline the clinical similarities and differences between LCHADD and TFPD, describe the course of the associated retinopathy, propose a genotype/phenotype correlation with the severity of retinopathy, and discuss the current theories about the etiology of the retinopathy.
AB - Although the retina is thought to primarily rely on glucose for fuel, inherited deficiency of one or more activities of mitochondrial trifunctional protein results in a pigmentary retinopathy leading to vision loss. Many other enzymatic deficiencies in fatty acid oxidation pathways have been described, none of which results in retinal complications. The etiology of retinopathy among patients with defects in trifunctional protein is unknown. Trifunctional protein is a heteroctomer; two genes encode the alpha and beta subunits of TFP respectively, HADHA and HADHB. A common mutation in HADHA, c.1528. G > C, leads to a single amino acid substitution, p. Glu474Gln, and impairs primarily long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity leading to LCHAD deficiency (LCHADD). Other mutations in HADHA or HADHB often lead to significant reduction in all three enzymatic activities and result in trifunctional protein deficiency (TFPD). Despite many similarities in clinical presentation and phenotype, there is growing evidence that they can result in different chronic complications. This review will outline the clinical similarities and differences between LCHADD and TFPD, describe the course of the associated retinopathy, propose a genotype/phenotype correlation with the severity of retinopathy, and discuss the current theories about the etiology of the retinopathy.
KW - Fatty acid oxidation
KW - Hydroxyacylcarnitines
KW - Inborn errors of metabolism
KW - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
KW - Mitochondrial trifunctional protein deficiency
KW - Retinopathy
UR - http://www.scopus.com/inward/record.url?scp=84860192534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860192534&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2012.02.015
DO - 10.1016/j.ymgme.2012.02.015
M3 - Review article
C2 - 22459206
AN - SCOPUS:84860192534
SN - 1096-7192
VL - 106
SP - 18
EP - 24
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
ER -