This report describes mitochondrial DNA depletion syndrome 4B (MNGIE type), one of several diseases associated with the human DNA polymerase gene POLG, which plays a role in replication of mitochondrial DNA. See the human disease model report for mtDNA polymerase disorders, POLG-related (FBhh0000432) 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 Nov. 2016 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 4B (MNGIE TYPE); MTDPS4B](https://omim.org/entry/613662)
[POLYMERASE, DNA, GAMMA; POLG](https://omim.org/entry/174763)
Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003; pubmed:20142534). [from MIM:613662; 2016.11.22]
MTDPS4B is caused by compound heterozygous mutation in the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG). [from MIM:613662; 2016.11.22]
