Rhabdomyolysis and Metabolic Myopathy

Gene: HADHB

Green List (high evidence)

The HADHA and HADHB genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in the beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase step. The beta subunit harbors the 3-ketoacyl-CoA thiolase activity.

Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy. Peripheral neuropathy also reported.

Well established gene-disease association.

Created: 2 May 2022, 1 a.m. | Last Modified: 2 May 2022, 1 a.m.

Panel Version: 0.13556

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trifunctional protein deficiency, MIM# 609015

Publications

• 30682426
• 28515471

Green List (high evidence)

The heterooctameric mitochondrial trifunctional protein (MTP), composed of four α- and β-subunits harbours three enzymes that each perform a different function in mitochondrial fatty acid β-oxidation. MTP deficiency is a defect in the substrate-generating upstream reactions of OXPHOS. >3 cases reported.
Sources: NHS GMS, Literature

Created: 21 Mar 2020, 8:02 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trifunctional protein deficiency MIM#609015

Publications

• 25778941
• 30682426
• 9259266
• 29956646