IllnessDeoxyguanosine Kinase Deficiency, mtDNA depletions syndrome, hepatocerebral; differential diagnosis

NGS +

Deoxyguanosine kinase deficiency is an inherited disorder that can cause liver disease and neurological problems in 2 forms. The majority of affected individuals have the more severe form, called hepatocerebral because of the severe problems in the liver and brain. Newborns with the hepatocerebral form of deoxyguanosine kinase deficiency may develop lactic acidosis with weakness, decreased activity and hypoglycemia in the first few days after birth as a result of liver dysfunction, which can lead to liver failure. They also develop progressive neurological problems such as severe hypotonia, nystagmus and developmental regression. Children with this form of the disorder usually do not survive longer than 2 years. In some affected individuals, a milder form occurs in which liver affliction is the main symptom. These patients may also develop renal problems and mild hypotonia as the only neurologic effect. ~100 affected individuals have been identified; 15-20% of all cases of mtDNA depletion are caused by DGUOK mutations. Decreased deoxyguanosine kinase activity leads to problems in mitochondrial DNA production and maintenance, and it is inherited in an autosomal recessive manner. The panel includes 21 guideline-curated genes. The DNA diagnostic yield is not known, and a negative molecular genetic test result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK7040/

• Alias: DGUOK Deficiency
• Alias: DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form
• Alias: Deoxyguanosine Kinase Deficiency
• Alias: Hepatocerebral mitochondrial DNA depletion syndrome
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Perrault syndrome 5 (TWNK)
• Alpers syndrome (POLG)
• Behr syndrome (OPA1)
• Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
• Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (DNM1L)
• GABA-transaminase deficiency (ABAT)
• Hereditary motor + sensory neuropathy VIA (MFN2)
• Mitochondrial DNA depletion syndrome 1 [MNGIE type] (TYMP)
• Mitochondrial DNA depletion syndrome 11 (MGME1)
• Mitochondrial DNA depletion syndrome 12A [cardiomyopathic type] (SLC25A4)
• Mitochondrial DNA depletion syndrome 12B [cardiomyopathic type] (SLC25A4)
• Mitochondrial DNA depletion syndrome 13 [encephalomyopathic type] (FBXL4)
• Mitochondrial DNA depletion syndrome 14 [encephalocardiomyopathic type] (OPA1)
• Mitochondrial DNA depletion syndrome 15 hepatocerebral type] (TFAM)
• Mitochondrial DNA depletion syndrome 18 (SLC25A21)
• Mitochondrial DNA depletion syndrome 2 [myopathic type] (TK2)
• Mitochondrial DNA depletion syndrome 3 [hepatocerebral type] (DGUOK)
• Mitochondrial DNA depletion syndrome 4A [Alpers type] (POLG)
• Mitochondrial DNA depletion syndrome 4B [MNGIE type] (POLG)
• Mitochondrial DNA depletion syndrome 5 [encephalomyopathy +/- methylmalonic aciduria] (SUCLA2)
• Mitochondrial DNA depletion syndrome 6 [hepatocerebral type] (MPV17)
• Mitochondrial DNA depletion syndrome 7 [hepatocerebral type] (TWNK)
• Mitochondrial DNA depletion syndrome 8A [encephalomyopathic type with renal tubulopathy] (RRM2B)
• Mitochondrial DNA depletion syndrome 8B [MNGIE type] (RRM2B)
• Mitochondrial DNA depletion syndrome 9 [encephalomyopathic type + methylmalonic aciduria] (SUCLG1)
• Mitochondrial recessive ataxia syndrome [includes SANDO + SCAE] (POLG)
• Myopathy, mitochondrial progressive, with congenital cataract + developmental delay (GFER)
• Optic atrophy 1 (OPA1)
• Optic atrophy 12 (AFG3L2)
• Optic atrophy 5 (DNM1L)
• Optic atrophy plus syndrome (OPA1)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 2 (SLC25A4)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 6 (DNA2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 3 (TK2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK)
• Progressive external ophthalmoplegia, AD 1 (POLG)
• Seckel syndrome 8 (DNA2)
• Sengers syndrome (AGK)
• Spastic ataxia 5, AR (AFG3L2)
• Spastic paraplegia 7, AR (SPG7)
• Spinocerebellar ataxia 28 (AFG3L2)
• mtDNA depletion syndrome (AGK)