This report describes Alpers-Huttenlocher syndrome (AHS), a mitochondrial disorder. AHS is one of several diseases associated with the human DNA polymerase gene POLG, which plays a role in replication of mitochondrial DNA; POLG is a nuclear-encoded gene. See the human disease model report for ‘mtDNA polymerase disorders, POLG-related’ (FBhh000432) for information on experimental results using Drosophila models of this and related diseases. See MIM:174763 for variants of POLG associated with this disease. OMIM includes this disease in the phenotypic series mitochondrial DNA depletion syndrome (FBhh0000440).
[updated Aug. 2020 by FlyBase; FBrf0222196]
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues without mutations or rearrangements in the mtDNA. MDS is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=35698.0 2016.11.23]
[MITOCHONDRIAL DNA DEPLETION SYNDROME 4A (ALPERS TYPE); MTDPS4A](https://omim.org/entry/203700)
[POLYMERASE, DNA, GAMMA; POLG](https://omim.org/entry/174763)
MTDPS4A, also known as Alpers-Huttenlocher syndrome, typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease. [Genetics Home Reference, Alpers-Huttenlocher syndrome; 2016.11.22]
The brain and liver are the classic organs affected by this disease due to their high energy demand and the proportional need for mitochondria. Decreased mitochondria in these organ systems lead to a variety of symptoms, with seizures and liver failure being the most common. This pathology is a rapidly progressive disease that presents early in life and invariably ends in a fatality. [Gene Reviews, Alpers-Huttenlocher Syndrome; 2020.08.12]
MTDPS4A is caused by homozygous or compound heterozygous mutation in the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG). [from MIM:203700; 2016.11.22]
