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Mitochondrial myopathy-lactic acidosis-deafness syndrome(MMLA)

MedGen UID:
343245
Concept ID:
C1855033
Disease or Syndrome
Synonyms: Metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness; Mitochondrial myopathy with lactic acidosis
Modes of inheritance:
No inheritance data available
MedGen UID:
989178
Concept ID:
CN307043
Finding
Source: Orphanet
No information is available in the scientific literature on heredity of the clinical entity.
 
Gene (location): PNPLA8 (7q31.1)
 
Monarch Initiative: MONDO:0016825
OMIM®: 251950
Orphanet: ORPHA2597

Definition

A rare metabolic myopathy presenting during childhood, and characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria. There have been no further descriptions in the literature since 1973. [from ORDO]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
Decreased CSF 5-methyltetrahydrofolate concentration
MedGen UID:
893131
Concept ID:
C4022901
Finding
A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Inborn mitochondrial myopathy
MedGen UID:
56484
Concept ID:
C0162670
Disease or Syndrome
A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Increased serum pyruvate
MedGen UID:
376596
Concept ID:
C1849488
Finding
An increased concentration of pyruvate in the blood.
Elevated serum anion gap
MedGen UID:
1671031
Concept ID:
C4732778
Finding
An abnormally high value of the serum anion gap (the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMitochondrial myopathy-lactic acidosis-deafness syndrome
Follow this link to review classifications for Mitochondrial myopathy-lactic acidosis-deafness syndrome in Orphanet.

Recent clinical studies

Etiology

Rudaks LI, Watson E, Oboudiyat C, Kumar KR, Sullivan P, Cowley MJ, Davis RL, Sue CM
Am J Med Genet A 2022 Jul;188(7):2226-2230. Epub 2022 Apr 8 doi: 10.1002/ajmg.a.62755. PMID: 35393742Free PMC Article
Tesarova M, Vondrackova A, Stufkova H, Veprekova L, Stranecky V, Berankova K, Hansikova H, Magner M, Galoova N, Honzik T, Vodickova E, Stary J, Zeman J
Pediatr Blood Cancer 2019 Apr;66(4):e27591. Epub 2018 Dec 26 doi: 10.1002/pbc.27591. PMID: 30588737
Torraco A, Stehling O, Stümpfig C, Rösser R, De Rasmo D, Fiermonte G, Verrigni D, Rizza T, Vozza A, Di Nottia M, Diodato D, Martinelli D, Piemonte F, Dionisi-Vici C, Bertini E, Lill R, Carrozzo R
Hum Mol Genet 2018 Aug 1;27(15):2739-2754. doi: 10.1093/hmg/ddy183. PMID: 29767723
Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giegé R, Bahlo M, Christodoulou J
Am J Hum Genet 2010 Jul 9;87(1):52-9. doi: 10.1016/j.ajhg.2010.06.001. PMID: 20598274Free PMC Article
De Vivo DC
Brain Dev 1993 Jan-Feb;15(1):1-22. doi: 10.1016/0387-7604(93)90002-p. PMID: 8338207

Diagnosis

Rudaks LI, Watson E, Oboudiyat C, Kumar KR, Sullivan P, Cowley MJ, Davis RL, Sue CM
Am J Med Genet A 2022 Jul;188(7):2226-2230. Epub 2022 Apr 8 doi: 10.1002/ajmg.a.62755. PMID: 35393742Free PMC Article
Beecher G, Fleming MD, Liewluck T
Muscle Nerve 2022 Apr;65(4):374-390. Epub 2022 Jan 5 doi: 10.1002/mus.27474. PMID: 34985130
Shahni R, Wedatilake Y, Cleary MA, Lindley KJ, Sibson KR, Rahman S
Am J Med Genet A 2013 Sep;161A(9):2334-8. Epub 2013 Aug 5 doi: 10.1002/ajmg.a.36065. PMID: 23918765Free PMC Article
Yoneda M, Ikawa M, Arakawa K, Kudo T, Kimura H, Fujibayashi Y, Okazawa H
Biochim Biophys Acta 2012 May;1820(5):615-8. Epub 2011 May 8 doi: 10.1016/j.bbagen.2011.04.018. PMID: 21600268
Finsterer J
Acta Haematol 2007;118(2):88-98. Epub 2007 Jul 18 doi: 10.1159/000105676. PMID: 17637511

Therapy

Yoneda M, Ikawa M, Arakawa K, Kudo T, Kimura H, Fujibayashi Y, Okazawa H
Biochim Biophys Acta 2012 May;1820(5):615-8. Epub 2011 May 8 doi: 10.1016/j.bbagen.2011.04.018. PMID: 21600268
Chariot P, Drogou I, de Lacroix-Szmania I, Eliezer-Vanerot MC, Chazaud B, Lombès A, Schaeffer A, Zafrani ES
J Hepatol 1999 Jan;30(1):156-60. doi: 10.1016/s0168-8278(99)80020-8. PMID: 9927163

Prognosis

Tesarova M, Vondrackova A, Stufkova H, Veprekova L, Stranecky V, Berankova K, Hansikova H, Magner M, Galoova N, Honzik T, Vodickova E, Stary J, Zeman J
Pediatr Blood Cancer 2019 Apr;66(4):e27591. Epub 2018 Dec 26 doi: 10.1002/pbc.27591. PMID: 30588737
Yoneda M, Ikawa M, Arakawa K, Kudo T, Kimura H, Fujibayashi Y, Okazawa H
Biochim Biophys Acta 2012 May;1820(5):615-8. Epub 2011 May 8 doi: 10.1016/j.bbagen.2011.04.018. PMID: 21600268
Finsterer J
Acta Haematol 2007;118(2):88-98. Epub 2007 Jul 18 doi: 10.1159/000105676. PMID: 17637511
Fernandez-Vizarra E, Berardinelli A, Valente L, Tiranti V, Zeviani M
J Med Genet 2007 Mar;44(3):173-80. Epub 2006 Oct 20 doi: 10.1136/jmg.2006.045252. PMID: 17056637Free PMC Article

Clinical prediction guides

Riley LG, Heeney MM, Rudinger-Thirion J, Frugier M, Campagna DR, Zhou R, Hale GA, Hilliard LM, Kaplan JA, Kwiatkowski JL, Sieff CA, Steensma DP, Rennings AJ, Simons A, Schaap N, Roodenburg RJ, Kleefstra T, Arenillas L, Fita-Torró J, Ahmed R, Abboud M, Bechara E, Farah R, Tamminga RYJ, Bottomley SS, Sanchez M, Huls G, Swinkels DW, Christodoulou J, Fleming MD
Haematologica 2018 Dec;103(12):2008-2015. Epub 2018 Jul 19 doi: 10.3324/haematol.2017.182659. PMID: 30026338Free PMC Article
Torraco A, Stehling O, Stümpfig C, Rösser R, De Rasmo D, Fiermonte G, Verrigni D, Rizza T, Vozza A, Di Nottia M, Diodato D, Martinelli D, Piemonte F, Dionisi-Vici C, Bertini E, Lill R, Carrozzo R
Hum Mol Genet 2018 Aug 1;27(15):2739-2754. doi: 10.1093/hmg/ddy183. PMID: 29767723
Finsterer J
Acta Haematol 2007;118(2):88-98. Epub 2007 Jul 18 doi: 10.1159/000105676. PMID: 17637511
Iizuka T, Sakai F
Curr Neurovasc Res 2005 Jan;2(1):29-45. doi: 10.2174/1567202052773544. PMID: 16181098
Inbal A, Avissar N, Shaklai M, Kuritzky A, Schejter A, Ben-David E, Shanske S, Garty BZ
Am J Med Genet 1995 Jan 30;55(3):372-8. doi: 10.1002/ajmg.1320550325. PMID: 7726239

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