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Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis(MMCKR)

MedGen UID:
1824033
Concept ID:
C5774260
Disease or Syndrome
Synonym: MMCKR
 
Gene (location): MLIP (6p12.1)
 
Monarch Initiative: MONDO:0859322
OMIM®: 620138

Definition

Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (MMCKR) is an autosomal recessive disorder of skeletal muscle characterized by the onset of muscle cramping and stiffness on exertion in infancy or early childhood, although later (even adult) onset has also been reported. The features remit with rest, but some individuals develop mild proximal or distal muscle weakness. Rare affected individuals may demonstrate cardiac involvement, including left ventricular dysfunction or rhythm abnormalities. Laboratory studies show increased baseline serum creatine kinase levels with episodic spikes that may coincide with rhabdomyolysis. EMG shows myopathic changes, and muscle biopsy shows nonspecific myopathic or degenerative features (Lopes Abath Neto et al., 2021; Salzer-Sheelo et al., 2022). [from OMIM]

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Hereditary myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
Distal upper limb muscle weakness
MedGen UID:
461970
Concept ID:
C3150620
Finding
Reduced strength of the distal musculature of the arms.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Rhabdomyolysis
MedGen UID:
19775
Concept ID:
C0035410
Pathologic Function
Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Progressive proximal muscle weakness
MedGen UID:
322841
Concept ID:
C1836156
Finding
Lack of strength of the proximal muscles that becomes progressively more severe.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Muscle fiber necrosis
MedGen UID:
376893
Concept ID:
C1850848
Pathologic Function
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
Exercise-induced muscle cramps
MedGen UID:
383715
Concept ID:
C1855578
Finding
Sudden and involuntary contractions of one or more muscles brought on by physical exertion.
Exercise-induced muscle stiffness
MedGen UID:
343388
Concept ID:
C1855579
Finding
A type of muscle stiffness that occurs following physical exertion.
Proximal muscle weakness in lower limbs
MedGen UID:
356423
Concept ID:
C1866010
Finding
A lack of strength of the proximal muscles of the legs.
Increased endomysial connective tissue
MedGen UID:
867771
Concept ID:
C4022161
Finding
An increased volume of the endomysium, which is a connective tissue sheath that surrounds each muscule fiber. Together, bundles of muscle fibers form a fasciculus, surrounded by another layer of connective tissue called the perimysium.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

Professional guidelines

PubMed

Bhai SF, Vissing J
Muscle Nerve 2023 Sep;68(3):250-256. Epub 2023 May 25 doi: 10.1002/mus.27840. PMID: 37226557
Brisca G, Mariani M, Pirlo D, Romanengo M, Pistorio A, Gaiero A, Panicucci C, Piccotti E, Bruno C
Ital J Pediatr 2021 Mar 9;47(1):57. doi: 10.1186/s13052-021-01002-x. PMID: 33750449Free PMC Article
Witting N, Laforêt P, Voermans NC, Roux-Buisson N, Bompaire F, Rendu J, Duno M, Feillet F, Kamsteeg EJ, Poulsen NS, Dahlqvist JR, Romero NB, Fauré J, Vissing J, Behin A
Acta Neurol Scand 2018 May;137(5):452-461. Epub 2017 Dec 29 doi: 10.1111/ane.12885. PMID: 29635721

Recent clinical studies

Etiology

Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Ra SG, Miyazaki T, Kojima R, Komine S, Ishikura K, Kawanaka K, Honda A, Matsuzaki Y, Ohmori H
J Sports Med Phys Fitness 2018 Nov;58(11):1582-1591. Epub 2017 Sep 22 doi: 10.23736/S0022-4707.17.07638-1. PMID: 28944645
Ahmad Z
Am J Cardiol 2014 May 15;113(10):1765-71. Epub 2014 Mar 2 doi: 10.1016/j.amjcard.2014.02.033. PMID: 24792743
Thompson PD, Clarkson P, Karas RH
JAMA 2003 Apr 2;289(13):1681-90. doi: 10.1001/jama.289.13.1681. PMID: 12672737
Bannwarth B
Expert Opin Drug Saf 2002 May;1(1):65-70. doi: 10.1517/14740338.1.1.65. PMID: 12904161

Diagnosis

Bhai SF, Vissing J
Muscle Nerve 2023 Sep;68(3):250-256. Epub 2023 May 25 doi: 10.1002/mus.27840. PMID: 37226557
Steinmeyer J, Flechtenmacher J
Z Orthop Unfall 2023 Apr;161(2):175-181. Epub 2021 Jul 28 doi: 10.1055/a-1488-6912. PMID: 34320661
Gooch C, Dean SJ, Marzullo L
Pediatr Emerg Care 2021 Dec 1;37(12):e1759-e1760. doi: 10.1097/PEC.0000000000002079. PMID: 32205805
Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Ahmad Z
Am J Cardiol 2014 May 15;113(10):1765-71. Epub 2014 Mar 2 doi: 10.1016/j.amjcard.2014.02.033. PMID: 24792743

Therapy

Steinmeyer J, Flechtenmacher J
Z Orthop Unfall 2023 Apr;161(2):175-181. Epub 2021 Jul 28 doi: 10.1055/a-1488-6912. PMID: 34320661
Chen HY, Chen YC, Tung K, Chao HH, Wang HS
J Appl Physiol (1985) 2019 Sep 1;127(3):798-805. Epub 2019 Jun 20 doi: 10.1152/japplphysiol.01108.2018. PMID: 31219772
Ahmad Z
Am J Cardiol 2014 May 15;113(10):1765-71. Epub 2014 Mar 2 doi: 10.1016/j.amjcard.2014.02.033. PMID: 24792743
Thompson PD, Clarkson P, Karas RH
JAMA 2003 Apr 2;289(13):1681-90. doi: 10.1001/jama.289.13.1681. PMID: 12672737
Bannwarth B
Expert Opin Drug Saf 2002 May;1(1):65-70. doi: 10.1517/14740338.1.1.65. PMID: 12904161

Prognosis

Cabrera-Serrano M, Caccavelli L, Savarese M, Vihola A, Jokela M, Johari M, Capiod T, Madrange M, Bugiardini E, Brady S, Quinlivan R, Merve A, Scalco R, Hilton-Jones D, Houlden H, Aydin HI, Ceylaner S, Drewes S, Vockley J, Taylor RL, Folland C, Kelly A, Goullee H, Ylikallio E, Auranen M, Tyynismaa H, Udd B, Forrest ARR, Davis MR, Bratkovic D, Manton N, Robertson T, O'Gorman C, McCombe P, Laing NG, Phillips L, de Lonlay P, Ravenscroft G
Brain 2022 Nov 21;145(11):3985-3998. doi: 10.1093/brain/awab484. PMID: 34957489
Lopes Abath Neto O, Medne L, Donkervoort S, Rodríguez-García ME, Bolduc V, Hu Y, Guadagnin E, Foley AR, Brandsema JF, Glanzman AM, Tennekoon GI, Santi M, Berger JH, Megeney LA, Komaki H, Inoue M, Cotrina-Vinagre FJ, Hernández-Lain A, Martin-Hernández E, Williams L, Borell S, Schorling D, Lin K, Kolokotronis K, Lichter-Konecki U, Kirschner J, Nishino I, Banwell B, Martínez-Azorín F, Burgon PG, Bönnemann CG
Brain 2021 Oct 22;144(9):2722-2731. doi: 10.1093/brain/awab275. PMID: 34581780Free PMC Article
Witting N, Laforêt P, Voermans NC, Roux-Buisson N, Bompaire F, Rendu J, Duno M, Feillet F, Kamsteeg EJ, Poulsen NS, Dahlqvist JR, Romero NB, Fauré J, Vissing J, Behin A
Acta Neurol Scand 2018 May;137(5):452-461. Epub 2017 Dec 29 doi: 10.1111/ane.12885. PMID: 29635721
Centers for Disease Control and Prevention (CDC)
MMWR Morb Mortal Wkly Rep 2011 Sep 2;60(34):1164-6. PMID: 21881547
Stoner GD
Am Fam Physician 2005 May 1;71(9):1723-30. PMID: 15887451

Clinical prediction guides

Li Q, Bao L, Liu M, Zhang R, Shi H, Chen H
Muscle Nerve 2023 Mar;67(3):231-236. Epub 2023 Jan 9 doi: 10.1002/mus.27781. PMID: 36576109
Masuda Y, Wam R, Paik B, Ngoh C, Choong AM, Ng JJ
Phys Sportsmed 2023 Aug;51(4):294-305. Epub 2022 Mar 10 doi: 10.1080/00913847.2022.2049645. PMID: 35254210
Lopes Abath Neto O, Medne L, Donkervoort S, Rodríguez-García ME, Bolduc V, Hu Y, Guadagnin E, Foley AR, Brandsema JF, Glanzman AM, Tennekoon GI, Santi M, Berger JH, Megeney LA, Komaki H, Inoue M, Cotrina-Vinagre FJ, Hernández-Lain A, Martin-Hernández E, Williams L, Borell S, Schorling D, Lin K, Kolokotronis K, Lichter-Konecki U, Kirschner J, Nishino I, Banwell B, Martínez-Azorín F, Burgon PG, Bönnemann CG
Brain 2021 Oct 22;144(9):2722-2731. doi: 10.1093/brain/awab275. PMID: 34581780Free PMC Article
Witting N, Laforêt P, Voermans NC, Roux-Buisson N, Bompaire F, Rendu J, Duno M, Feillet F, Kamsteeg EJ, Poulsen NS, Dahlqvist JR, Romero NB, Fauré J, Vissing J, Behin A
Acta Neurol Scand 2018 May;137(5):452-461. Epub 2017 Dec 29 doi: 10.1111/ane.12885. PMID: 29635721
Centers for Disease Control and Prevention (CDC)
MMWR Morb Mortal Wkly Rep 2011 Sep 2;60(34):1164-6. PMID: 21881547

Recent systematic reviews

Masuda Y, Wam R, Paik B, Ngoh C, Choong AM, Ng JJ
Phys Sportsmed 2023 Aug;51(4):294-305. Epub 2022 Mar 10 doi: 10.1080/00913847.2022.2049645. PMID: 35254210
Kruijt N, van den Bersselaar LR, Wijma J, Verbeeck W, Coenen MJH, Neville J, Snoeck M, Kamsteeg EJ, Jungbluth H, Kramers C, Voermans NC
Neuromuscul Disord 2020 Dec;30(12):949-958. Epub 2020 Oct 31 doi: 10.1016/j.nmd.2020.10.010. PMID: 33250373
Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S
Clin Toxicol (Phila) 2016;54(1):1-13. Epub 2015 Nov 15 doi: 10.3109/15563650.2015.1110590. PMID: 26567470
von Vigier RO, Ortisi MT, La Manna A, Bianchetti MG, Bettinelli A
Pediatr Nephrol 2010 May;25(5):861-6. Epub 2009 Dec 22 doi: 10.1007/s00467-009-1388-2. PMID: 20033223
Wojtowicz JM, Yarema MC, Wax PM
CJEM 2008 Jan;10(1):69-74. doi: 10.1017/s1481803500010034. PMID: 18226321

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