Fatty Acid Oxidation Defects

Gene: HSD17B10

Green List (high evidence)

The HSD17B10 gene encodes 17-beta-hydroxysteroid dehydrogenase X, a member of the short-chain dehydrogenase/reductase superfamily. It is a multifunctional mitochondrial enzyme that acts on a wide spectrum of substrates, including neuroactive steroids, isoleucine, and fatty acids, with a preference for short-chain methyl-branched acyl-CoAs.

HSD10 mitochondrial disease most commonly presents as an X-linked neurodegenerative disorder with highly variable severity and age at onset ranging from the neonatal period to early childhood. The features are usually multisystemic, consistent with mitochondrial dysfunction. Some affected males have a severe infantile form associated with cardiomyopathy that may result in death in early childhood, whereas other rare patients may have juvenile onset or even atypical presentations with normal neurologic development. More severely affected males show developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation. Heterozygous females may show non-progressive developmental delay and intellectual disability, but may also be clinically normal.

Multiple unrelated families reported.

Created: 3 Jan 2021, 11:43 p.m. | Last Modified: 3 Jan 2021, 11:43 p.m.

Panel Version: 0.78

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
HSD10 mitochondrial disease 300438