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Mitochondrial DNA depletion syndrome 17(MTDPS17)

MedGen UID:
1684823
Concept ID:
C5231412
Disease or Syndrome
Synonyms: MITOCHONDRIAL DNA DEPLETION SYNDROME 17; MTDPS17
 
Gene (location): MRM2 (7p22.3)
 
Monarch Initiative: MONDO:0032815
OMIM®: 618567

Definition

Mitochondrial depletion syndrome-17 (MTDPS17) is an autosomal recessive dystonic or movement disorder (summary by Shafique et al., 2023). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). [from OMIM]

Clinical features

From HPO
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Epilepsia partialis continua
MedGen UID:
39303
Concept ID:
C0085543
Disease or Syndrome
Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years).
Hemiballismus
MedGen UID:
67443
Concept ID:
C0221169
Finding
Hemiballismus is a rare movement disorder that is caused primarily by damage to various areas in the basal ganglia. Hemiballismus is usually characterized by involuntary flinging motions of the extremities. The movements are often violent and have wide amplitudes of motion. They are continuous and random and can involve proximal and/or distal muscles on one side of the body, while some cases even include the facial muscles. The more a patient is active, the more the movements increase. With relaxation comes a decrease in movements.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Acidosis
MedGen UID:
1296
Concept ID:
C0001122
Pathologic Function
Abnormal acid accumulation or depletion of base.
Low plasma citrulline
MedGen UID:
326522
Concept ID:
C1839532
Finding
A decreased concentration of citrulline in the blood.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.
Decreased activity of mitochondrial complex I
MedGen UID:
393796
Concept ID:
C2677650
Finding
A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.
Decreased activity of mitochondrial complex IV
MedGen UID:
866520
Concept ID:
C4020800
Finding
A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria.

Professional guidelines

PubMed

Amtmann D, Gammaitoni AR, Galer BS, Salem R, Jensen MP
Mitochondrion 2023 Jan;68:1-9. Epub 2022 Oct 29 doi: 10.1016/j.mito.2022.10.003. PMID: 36374792

Recent clinical studies

Etiology

Amtmann D, Gammaitoni AR, Galer BS, Salem R, Jensen MP
Mitochondrion 2023 Jan;68:1-9. Epub 2022 Oct 29 doi: 10.1016/j.mito.2022.10.003. PMID: 36374792
Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T
Biochim Biophys Acta 2012 May;1820(5):632-6. Epub 2011 Aug 11 doi: 10.1016/j.bbagen.2011.08.006. PMID: 21855607
Ashley N, O'Rourke A, Smith C, Adams S, Gowda V, Zeviani M, Brown GK, Fratter C, Poulton J
Hum Mol Genet 2008 Aug 15;17(16):2496-506. Epub 2008 May 16 doi: 10.1093/hmg/ddn150. PMID: 18487244Free PMC Article
Miró O, López S, Pedrol E, Rodríguez-Santiago B, Martínez E, Soler A, Milinkovic A, Casademont J, Nunes V, Gatell JM, Cardellach F
Antivir Ther 2003 Aug;8(4):333-8. PMID: 14526764
Nolan D, Hammond E, Martin A, Taylor L, Herrmann S, McKinnon E, Metcalf C, Latham B, Mallal S
AIDS 2003 Jun 13;17(9):1329-38. doi: 10.1097/00002030-200306130-00007. PMID: 12799554

Diagnosis

Moragues-Solanas L, Le-Viet T, McSorley E, Halford C, Lockhart DS, Aydin A, Kay GL, Elumogo N, Mullen W, O'Grady J, Gilmour MW
BMC Med Genomics 2024 Mar 5;17(1):71. doi: 10.1186/s12920-024-01835-5. PMID: 38443925Free PMC Article
Uchida H, Sakamoto S, Shimizu S, Yanagi Y, Fukuda A, Horikawa R, Ito R, Matsunaga A, Murayama K, Kasahara M
Pediatr Transplant 2021 Dec;25(8):e14091. Epub 2021 Jul 15 doi: 10.1111/petr.14091. PMID: 34265160
Hong KT, Lim BC, Moon JS, Ko JS
Korean J Gastroenterol 2021 May 25;77(5):248-252. doi: 10.4166/kjg.2020.170. PMID: 34035203
McKiernan P, Ball S, Santra S, Foster K, Fratter C, Poulton J, Craig K, McFarland R, Rahman S, Hargreaves I, Gupte G, Sharif K, Taylor RW
J Pediatr Gastroenterol Nutr 2016 Dec;63(6):592-597. doi: 10.1097/MPG.0000000000001345. PMID: 27482763Free PMC Article
Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T
Biochim Biophys Acta 2012 May;1820(5):632-6. Epub 2011 Aug 11 doi: 10.1016/j.bbagen.2011.08.006. PMID: 21855607

Therapy

Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T
Biochim Biophys Acta 2012 May;1820(5):632-6. Epub 2011 Aug 11 doi: 10.1016/j.bbagen.2011.08.006. PMID: 21855607
Pronicka E, Weglewska-Jurkiewicz A, Pronicki M, Sykut-Cegielska J, Kowalski P, Pajdowska M, Jankowska I, Kotulska K, Kalicinski P, Jakobkiewicz-Banecka J, Wegrzyn G
Med Sci Monit 2011 Apr;17(4):CR203-9. doi: 10.12659/msm.881716. PMID: 21455106Free PMC Article
Kaji S, Murayama K, Nagata I, Nagasaka H, Takayanagi M, Ohtake A, Iwasa H, Nishiyama M, Okazaki Y, Harashima H, Eitoku T, Yamamoto M, Matsushita H, Kitamoto K, Sakata S, Katayama T, Sugimoto S, Fujimoto Y, Murakami J, Kanzaki S, Shiraki K
Mol Genet Metab 2009 Aug;97(4):292-6. Epub 2009 May 12 doi: 10.1016/j.ymgme.2009.04.014. PMID: 19520594
Miró O, López S, Pedrol E, Rodríguez-Santiago B, Martínez E, Soler A, Milinkovic A, Casademont J, Nunes V, Gatell JM, Cardellach F
Antivir Ther 2003 Aug;8(4):333-8. PMID: 14526764
Nolan D, Hammond E, Martin A, Taylor L, Herrmann S, McKinnon E, Metcalf C, Latham B, Mallal S
AIDS 2003 Jun 13;17(9):1329-38. doi: 10.1097/00002030-200306130-00007. PMID: 12799554

Prognosis

Grabhorn E, Tsiakas K, Herden U, Fischer L, Freisinger P, Marquardt T, Ganschow R, Briem-Richter A, Santer R
Liver Transpl 2014 Apr;20(4):464-72. Epub 2014 Feb 25 doi: 10.1002/lt.23830. PMID: 24478274
Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kuciński I, Ginalski K, Dziembowski A
Genes Dev 2012 Sep 1;26(17):1911-25. Epub 2012 Aug 16 doi: 10.1101/gad.193169.112. PMID: 22899009Free PMC Article
Pronicka E, Weglewska-Jurkiewicz A, Pronicki M, Sykut-Cegielska J, Kowalski P, Pajdowska M, Jankowska I, Kotulska K, Kalicinski P, Jakobkiewicz-Banecka J, Wegrzyn G
Med Sci Monit 2011 Apr;17(4):CR203-9. doi: 10.12659/msm.881716. PMID: 21455106Free PMC Article
Uusimaa J, Hinttala R, Rantala H, Päivärinta M, Herva R, Röyttä M, Soini H, Moilanen JS, Remes AM, Hassinen IE, Majamaa K
Epilepsia 2008 Jun;49(6):1038-45. Epub 2008 Feb 20 doi: 10.1111/j.1528-1167.2008.01544.x. PMID: 18294203
Chan SS, Longley MJ, Naviaux RK, Copeland WC
DNA Repair (Amst) 2005 Dec 8;4(12):1381-9. Epub 2005 Sep 21 doi: 10.1016/j.dnarep.2005.08.010. PMID: 16181814

Clinical prediction guides

Amtmann D, Gammaitoni AR, Galer BS, Salem R, Jensen MP
Mitochondrion 2023 Jan;68:1-9. Epub 2022 Oct 29 doi: 10.1016/j.mito.2022.10.003. PMID: 36374792
Shafique A, Arif B, Chu ML, Moran E, Hussain T, Zamora FM, Wohler E, Sobreira N, Klein C, Lohmann K, Naz S
J Med Genet 2023 Apr;60(4):352-358. Epub 2022 Aug 24 doi: 10.1136/jmg-2022-108521. PMID: 36002240
Uchida H, Sakamoto S, Shimizu S, Yanagi Y, Fukuda A, Horikawa R, Ito R, Matsunaga A, Murayama K, Kasahara M
Pediatr Transplant 2021 Dec;25(8):e14091. Epub 2021 Jul 15 doi: 10.1111/petr.14091. PMID: 34265160
Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T
Biochim Biophys Acta 2012 May;1820(5):632-6. Epub 2011 Aug 11 doi: 10.1016/j.bbagen.2011.08.006. PMID: 21855607
Chan SS, Longley MJ, Naviaux RK, Copeland WC
DNA Repair (Amst) 2005 Dec 8;4(12):1381-9. Epub 2005 Sep 21 doi: 10.1016/j.dnarep.2005.08.010. PMID: 16181814

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