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FB2026_01
,
released March 12, 2026
This report describes a potential model of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD); LCHAD is inherited as an autosomal recessive. The human gene implicated in this disease is HADHA, which encodes the alpha subunit of the mitochondrial trifunctional protein. In LCHAD, there is an isolated deficiency of the dehydrogenase activity with normal hydratase activity and moderately decreased thiolase activity. HADHA is also associated with the human disease mitochondrial trifunctional protein deficiency 1 (MTPD1; MIM:609015, FBhh0000337), which occurs when all three enzymatic functions are compromised. There is one fly ortholog, Mtpα, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated.
A UAS construct of the wild-type human Hsap\HADHA gene has been introduced into flies, but has not been characterized.
In flies, an amorphic allele of Mtpα has been used to model the more severe MTPD; see 'mitochondrial trifunctional protein deficiency 1' (FBhh0000337).
[updated May 2025 by FlyBase; FBrf0222196]
[LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY](https://omim.org/entry/609016)
[HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA](https://omim.org/entry/600890)
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly while fasting.
Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood and can include feeding difficulties, lethargy, hypoglycemia, hypotonia, liver problems, and abnormalities in the retina. Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue, and peripheral neuropathy). Individuals with LCHAD deficiency are also at risk for serious heart problems, breathing difficulties, coma, and sudden death. Problems related to LCHAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections.[From Genetics Home Reference, long-chain-hydroxyacyl-CoA dehydrogenase deficiency, 2016.06.16]
Isolated deficiency of long-chain 3-hydroxyl-CoA dehydrogenase (LCHAD) is an autosomal recessive disorder characterized by early-onset cardiomyopathy, hypoglycemia, neuropathy, and pigmentary retinopathy, and sudden death (IJlst et al., 1996, pubmed:8770876). [From MIM:609016, 2016.06.16]
LCHAD deficiency is caused by homozygous or compound heterozygous mutations in HADHA, the gene encoding long-chain hydroxyacyl-CoA dehydrogenase.
Complete mitochondrial trifunctional protein deficiency (MIM:609015) is a less common disorder that is also caused by mutation in the HADHA gene. [From MIM:609016, 2016.06.16]
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 mitochondrial beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) step. The alpha subunit harbors the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities (Kamijo et al., 1994, pubmed:8135828). [From MIM:600890, 2016.06.16]
One to one: 1 human to 1 Drosophila.