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Myopathy with lactic acidosis, hereditary(HML)

MedGen UID:
342573
Concept ID:
C1850718
Disease or Syndrome
Synonyms: HML
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
SNOMED CT: Myopathy with deficiency of succinate dehydrogenase and aconitase (699268002); Myopathy with deficiency of iron-sulphur cluster assembly enzyme (699268002); Myoglobinuria due to abnormal glycolysis (699268002); Hereditary myopathy with lactic acidosis (699268002); Myopathy with exercise intolerance, Swedish type (699268002); Myopathy with deficiency of iron-sulfur cluster assembly enzyme (699268002)
 
Gene (location): ISCU (12q23.3)
OMIM®: 255125
Orphanet: ORPHA43115

Disease characteristics

Excerpted from the GeneReview: Myopathy with Deficiency of ISCU
Myopathy with deficiency of ISCU, a mitochondrial myopathy, is classically characterized by lifelong exercise intolerance in which minor exertion causes tachycardia, shortness of breath, fatigue, and pain of active muscles; episodes of more profound exercise intolerance associated with rhabdomyolysis, myoglobinuria, and weakness that may be severe; and typically full recovery of muscle strength between episodes of rhabdomyolysis. Affected individuals usually have near-normal strength; they can have large calves. [from GeneReviews]
Authors:
Fanny Mochel  |  Ronald G Haller   view full author information

Additional descriptions

From OMIM
Hereditary myopathy with lactic acidosis is an autosomal recessive muscular disorder characterized by childhood onset of exercise intolerance with muscle tenderness, cramping, dyspnea, and palpitations. Biochemical features include lactic acidosis and, rarely, rhabdomyolysis. It is a chronic disorder with remission and exacerbation of the muscle phenotype (summary by Sanaker et al., 2010).  http://www.omim.org/entry/255125
From GHR
Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles used for movement (skeletal muscles). This condition does not usually affect other types of muscle, such as the heart (cardiac) muscle.From early childhood, affected individuals experience extreme fatigue in response to physical activity (exercise intolerance). Mild exertion results in a rapid heartbeat (tachycardia), shortness of breath, and muscle weakness and pain. However, people with this condition typically have normal muscle strength when they are at rest.Prolonged or recurrent physical activity causes more severe signs and symptoms, including a breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure.In most affected individuals, the muscle problems associated with this condition do not worsen with time. However, at least two people with a severe variant of this disorder have experienced progressive muscle weakness and wasting starting in childhood.  http://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme

Clinical features

Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Sideroblastic anemia
MedGen UID:
8067
Concept ID:
C0002896
Disease or Syndrome
Sideroblastic anemia results from a defect in the incorporation of iron into the heme molecule. A sideroblast is an erythroblast that has stainable deposits of iron in cytoplasm (this can be demonstrated by Prussian blue staining).
Myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
Respiratory difficulties
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing.
Muscle cramps
MedGen UID:
7749
Concept ID:
C0026821
Sign or Symptom
Muscle cramps are sudden, involuntary contractions or spasms in one or more of your muscles. They often occur after exercise or at night, lasting a few seconds to several minutes. It is a very common muscle problem. . Muscle cramps can be caused by nerves that malfunction. Sometimes this malfunction is due to a health problem, such as a spinal cord injury or a pinched nerve in the neck or back. Other causes are. -Straining or overusing a muscle. -Dehydration. -A lack of minerals in your diet or the depletion of minerals in your body. -Not enough blood getting to your muscles. Cramps can be very painful. Stretching or gently massaging the muscle can relieve this pain. .
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
Your muscles help you move and help your body work. Different types of muscles have different jobs. There are many problems that can affect muscles. Muscle disorders can cause weakness, pain or even paralysis. . Causes of muscle disorders include. -Injury or overuse, such as sprains or strains, cramps or tendinitis . -A genetic disorder, such as muscular dystrophy. -Some cancers. -Inflammation, such as myositis. -Diseases of nerves that affect muscles. -Infections. -Certain medicines. Sometimes the cause is not known.
Rhabdomyolysis
MedGen UID:
19775
Concept ID:
C0035410
Pathologic Function
Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Mitochondrial myopathy
MedGen UID:
56484
Concept ID:
C0162670
Disease or Syndrome
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA). While some mitochondrial disorders only affect a single organ (e.g., the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene POLG, which has emerged as a major cause of mitochondrial disease. Common clinical features of mitochondrial disease – whether involving a mitochondrial or nuclear gene – include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. A high incidence of mid- and late pregnancy loss is a common occurrence that often goes unrecognized.
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A reduction in the ability to perform or withstand activities that induce physical or mental exertion.
Increased intramyocellular lipid droplets
MedGen UID:
866481
Concept ID:
C4020730
Finding
An abnormal increase in intracellular lipid droplets In a muscle. The number and size of these drops can increase with somd disorders of lipid metabolism affecting muscle. See pmid 20691590 for histological images.
Subsarcolemmal accumulations of abnormally shaped mitochondria
MedGen UID:
871128
Concept ID:
C4025597
Anatomical Abnormality
An abnormally increased number of mitochondria in the cytoplasma adjacent to the sarcolemma (muscle cell membrane), whereby the mitochondria also possess an abnormal morphology.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.
Myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
CREATINE PHOSPHOKINASE INCREASED
MedGen UID:
57470
Concept ID:
C0151576
Finding
A laboratory test result which indicates increased levels of creatine phosphokinase in a biological specimen.
Increased serum lactate
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism.
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 III
MedGen UID:
460434
Concept ID:
C3149083
Finding
A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria.
Abnormal iron deposition in mitochondria
MedGen UID:
462906
Concept ID:
C3151556
Finding
Decreased activity of mitochondrial complex II
MedGen UID:
866521
Concept ID:
C4020801
Disease or Syndrome
A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMyopathy with lactic acidosis, hereditary
Follow this link to review classifications for Myopathy with lactic acidosis, hereditary in Orphanet.

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