Table 2.

Mitochondrial DNA Depletion Syndromes

Phenotype 1GeneDisorder / PhenotypeAdditional Common Manifestations 2
Hepatocerebral
(Encephalo-hepatopathic) 		DGUOK DGUOK deficiencyDD, hypotonia, nystagmus, lactic acidosis
POLG Alpers-Huttenlocher syndrome DD, psychomotor regression, epilepsy, hearing impairment
MPV17 MPV17 deficiency DD, hypotonia, poor weight gain, hearing impairment, lactic acidosis
TFAM Encephalohepatopathy (OMIM 617156)IUGR, hypoglycemia
TWNK Encephalohepatopathy (OMIM 271245)DD, hypotonia, lactic acidosis
Encephalo-
myopathic 		ABAT Encephalomyopathy w/↑ GABA (OMIM 613163)DD, hypotonia, epilepsy, ↑ GABA in plasma, urine, & CSF
FBXL4 FBXL4 deficiency DD, hypotonia, epilepsy, hearing impairment, lactic acidosis
OPA1 Encephalomyopathy (OMIM 616896)DD, HCM, optic atrophy
RNASEH1 Encephalomyopathy (OMIM 616479)Ophthalmoplegia, ptosis, ataxia
RRM2B RRM2B encephalomyopathic MDMD DD, hypotonia, GI dysmotility, renal tubulopathy
SUCLA2 SUCLA2 deficiency DD, hypotonia, dystonia, hearing impairment, ↑ methylmalonic acid
SUCLG1 SUCLG1 deficiency DD, hypotonia, hearing impairment, ↑ methylmalonic acid
Neurogastro-
intestinal
encephalopathic 		POLG MNGIE type 4B GI dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, muscle weakness, leukoencephalopathy 3
RRM2B MNGIE type 8B
TYMP MNGIE type 1
Myopathic AGK Sengers syndrome (OMIM 212350)Hypotonia, HCM, cataracts
MGME1 Myopathy (OMIM 615084)Ptosis, ophthalmoplegia
TK2 TK2 deficiency Hypotonia, loss of acquired motor skills
Encephalo-
neuropathic 		TWNK Infantile-onset spinocerebellar ataxia Hypotonia, hearing impairment

CSF = cerebrospinal fluid; DD = developmental delay; GI = gastrointestinal; HCM = hypertrophic cardiomyopathy; IUGR = intrauterine growth restriction; MDMD = mitochondrial DNA maintenance defect; MNGIE = mitochondrial neurogastrointestinal encephalopathy

1.

Within each phenotypic category, mtDNA depletion syndromes are ordered by relative prevalence.

2.

Common manifestations seen in addition to the primary phenotype (i.e., in addition to encephalohepatopathy, encephalomyopathy, etc.).

3.

Leukoencephalopathy is not present in POLG-related neurogastrointestinal encephalopathy.

From: Deoxyguanosine Kinase Deficiency

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