Mitochondrial diseases are heterogeneous and multifaceted, and can present at any age. [bcmj.org]

The age of diagnosis was also correlated with clinical presentation ( Table 3 ). [nature.com]

A generalized myopathy is present in most affected individuals, leading to early fatigue and exercise intolerance. [annalsofian.org]

There is a reported case of multiple, different mtDNA deletions present in two brothers with Pearson's syndrome, as well as in their asymptomatic mother (9). No mtDNA mutations were detected in the mother of the present patient. [path.upmc.edu]

MELAS Presents with sudden onset of strokes, usually precipitated by focal or generalized seizures. Usually has its onset in childhood, but can present at any age. [clinicaladvisor.com]

• Developmental Delay

  Significant developmental delay and intellectual disability are observed in most patients who survive infancy. [mendelian.co]

  A severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. [nectarmutation.org]

  In one form of ‘hepatocerebral’ depletion known as Alpers’ disease or Progressive Neuronal Degeneration of Childhood (PNDC), explosive onset of seizures, developmental delay and spasticity are followed some variable time later by catastrophic liver failure [newcastle-mitochondria.com]

  delay Hypothyroidism Inborn errors of metabolism Lysosomal storage diseases Muscular dystrophy Adults Chronic demyelinating disease Coenzyme Q disease Connective tissue diseases Dementia Infectious – fungal, viral Migraine disorder Multiple sclerosis [arupconsult.com]

  Physical therapy, occupational therapy, speech therapy, vision therapy, and developmental therapy are all indicated for developmental delays, spasticity management, and overall rehabilitation. [childneurologyfoundation.org]

• Anemia

  FINAL DIAGNOSIS: - PEARSON'S SYNDROME (Sideroblastic Anemia with Marrow Cell Vacuolization and Exocrine Pancreatic Dysfunction) Contributors' Note: In 1979, Pearson et al (1) reported the case of a young infant who presented with refractory anemia, marked [path.upmc.edu]

  The method of claim 1, wherein the mitochondrial disease or disorder is selected from the group consisting of Alexander disease, Alpers Syndrome, Alpha- ketoglutarate dehydrogenase (AKDGH) deficiency, ALS-FTD, Sideroblastic anemia with spinocerebellar [brevets-patents.ic.gc.ca]

  Sideroblastic anemia is defined by the presence of anemia and ringed sideroblasts in the bone marrow. [ncbi.nlm.nih.gov]

  Major deletions are also found in an infantile anemia, the Pearson syndrome. [medlink.com]

  […] alopecia Endocrine – diabetes mellitus, adrenal failure, growth failure, hypothyroidism, hypogonadism, hypoparathyroidism Gastrointestinal – vomiting, failure to thrive, dysphagia, gastrointestinal motility problems, pseudoobstruction Hematologic – anemia [arupconsult.com]

• Malnutrition

  Cirrhosis Dysmetria Skeletal muscle hypertrophy Malabsorption Abnormality of the nervous system Elevated hepatic transaminase Intellectual disability, mild Delayed speech and language development Hepatomegaly Spontaneous esophageal perforation Gastroparesis Malnutrition [mendelian.co]

  Patients with a PDH mutation are more susceptible to malnutrition as well as infection and other periods of increased energy demands. [clinicaladvisor.com]

• Recurrent Respiratory Infection

  respiratory infections Sclerotic scapulae Neonatal hypotonia Broad clavicles Respiratory tract infection 2-3 finger syndactyly Sclerotic vertebral endplates Dental crowding Trigeminal neuralgia Nasal speech Poor head control Dental malocclusion Kyphosis [mendelian.co]

• Failure to Thrive

  Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. [nectarmutation.org]

  Symptoms: Encephalomyopathy and various manifestations, including failure to thrive, developmental delay, hyoptonia, lethargy, respiratory failure, ataxia, myoclonus. Lactic acidosis common. May cause Leigh Syndrome. [umdf.org]

  […] to thrive 1. [ncbi.nlm.nih.gov]

  In pediatric mitochondrial disease, a broad spectrum of findings may be present, including lethargy, hypotonia, failure to thrive, seizures, cardiomyopathy, deafness, blindness, movement disorder, and lactic acidosis. [bcmj.org]

  Children with Pearson's syndrome characteristically present in early infancy with pallor, failure to thrive, pancytopenia, diarrhea, and markedly increased serum and/or cerebrospinal fluid lactate. [path.upmc.edu]

• Strabismus

  "The management of strabismus in patients with chronic progressive external ophthalmoplegia". Strabismus. 18 (2): 41–7. doi : 10.3109/09273971003758388. PMID 20521878. [en.wikipedia.org]

  METHODS: Strabismus surgery using the adjustable suture technique was performed in three patients with strabismus and chronic progressive external ophthalmoplegia confirmed by clinical, biochemical, histopathologic, and genetic criteria. [thedoctorsdoctor.com]

  Surgical management of strabismus associated with chronic progressive external ophthalmoplegia. Ophthalmology. 1997 Apr. 104(4):695-700. [Medline]. Ewart RM, Burrows RF. Pregnancy in chronic progressive external ophthalmoplegia: a case report. [emedicine.medscape.com]

  SCLEROSTEOSIS 1; SOST1 Is also known as sost, cortical hyperostosis with syndactyly;cortical hyperostosis-syndactyly syndrome Related symptoms: Autosomal recessive inheritance Hearing impairment Hypertelorism Nystagmus Strabismus SOURCES: MONDO UMLS SCTID [mendelian.co]

• Hearing Problem

  The most common symptoms are: Poor growth Loss of muscle coordination, muscle weakness Neurological problems, seizures Autism, autistic spectrum, autistic-like features Visual and/or hearing problems Developmental delays, learning disabilities Heart, [mitoaction.org]

  problems, reduced mental functions, hypotonia, disease of the organ, dementia, respiratory problems, hypoglycemia, apnea, lactic acidosis, seizures, swallowing difficulties, developmental delays, movement disorders (dystonia, muscle spasms, tremors, [brevets-patents.ic.gc.ca]

• Low Set Ears

  Examination revealed dysmorphism in the form of low set ears, high arched palate, and hallus valgus. He had bilateral ptosis with external ophthalmoplegia [Figure 1] a. Fundi and pupils were normal. [annalsofian.org]

  Ventriculomegaly Talipes equinovarus Macrocephaly Megalencephaly Neoplasm Acrania Pointed chin Fibroma Nystagmus Cataract Nevus Agenesis of corpus callosum Sporadic Myopia Facial asymmetry Cryptorchidism High palate Delayed speech and language development Low-set [mendelian.co]

• Myalgia

  […] summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6, is also known as progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 6, and has symptoms including muscle cramp, myalgia [malacards.org]

  Levator 10 50 2 Single mtDNA deletion 5.0-kb common deletion 13 No −4 Severe None Levator 10 42 3 Single mtDNA deletion 5.0-kb common deletion 27 No −3 Severe None Levator 1 28 4 Single mtDNA deletion 4.1-kb deletion 19 No −3 Moderate Mild myopathy, myalgia [iovs.arvojournals.org]

  Symptoms can range from mild cramps to more-severe myalgias, pain, and weakness. Rhabdomyolosis has also been reported in rare cases. [clevelandclinicmeded.com]

  Exertional myalgia Exertional myalgia is a common presenting symptom of mitochondrial disease, especially in adults. A 40-year-old man presented with exertional myalgias dating back to the age of 14. [bcmj.org]

  […] congenital myotonia; acz-responsive myotonia; acetazolamide-responsive congenital myotonia; myotonia-painful contractions syndrome; painful congenital myotonia; painful myotonia Related symptoms: Gait disturbance Dysphagia Hypertonia Hypothyroidism Myalgia [mendelian.co]

• Diffuse Muscle Wasting

  Clinical examination indicated cachexia (39 kg, 166 cm), diffuse muscle wasting, abdominal distention, bilateral external ophthalmoplegia, ptosis, gait ataxia, and lower limb hypoesthesia. [em-consulte.com]

• Severe Short Stature

  An XRCC4 splice mutation associated with severe short stature, gonadal failure, and early-onset metabolic syndrome. J Clin Endocrinol Metab. 2015; 100:E789–98. DOI: 10.1210/jc.2015-1098. PMID: 25742519. [e-sciencecentral.org]

• Hip Dislocation

  Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. [mendelian.co]

• Nystagmus

  Lower limb pain and amyotrophy may be present, as well as various cerebellar signs, including dysarthria, nystagmus, hypometric saccades and tremor. [mendelian.co]

  In addition, each syndrome is associated with characteristic features, such as nystagmus or ptosis. [medical-dictionary.thefreedictionary.com]

  In some cases, affected individuals may also experience night blindness; rapid, involuntary eye movements (nystagmus); and a decrease in the sharpness of vision (visual acuity). [rarediseases.org]

• Tremor

  Lower limb pain and amyotrophy may be present, as well as various cerebellar signs, including dysarthria, nystagmus, hypometric saccades and tremor. [mendelian.co]

  […] hearing) problems, reduced mental functions, hypotonia, disease of the organ, dementia, respiratory problems, hypoglycemia, apnea, lactic acidosis, seizures, swallowing difficulties, developmental delays, movement disorders (dystonia, muscle spasms, tremors [brevets-patents.ic.gc.ca]

  […] dysphagia, anorexia, abdominal pain, diarrhea Musculoskeletal – rhabdomyolysis, muscle weakness, exercise intolerance Neurologic – migraine, stroke, seizures, dementia, myopathy, peripheral neuropathy, ataxia, speech disturbances, bulbar signs, myoclonus, tremor [arupconsult.com]

  Patients can have other symptoms such as cardiac arrhythmias, Postural tremor, Peripheral neuropathy, Nonspecific myopathy, or Movement disorder. A multiple sclerosis-like process may develop, predominantly in Caucasian females. [clinicaladvisor.com]

• Hyporeflexia

  SPINOCEREBELLAR ATAXIA TYPE 43 Is also known as sca43 Related symptoms: Pain Dysarthria Hyporeflexia Areflexia Pes cavus SOURCES: ORPHANET More info about SPINOCEREBELLAR ATAXIA TYPE 43 Low match PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL [mendelian.co]

  Age of Onset Prevalence Manifestation Frequency Age (infantile onset) 61/89 (69%) Hypotonia 55/57 (96%) Elevated serum CK 56/59 (95%) Respiratory difficulties 48/53 (91%) Loss of previously acquired motor skills 43/49 (88%) mtDNA depletion 33/40 (83%) Hyporeflexia [ncbi.nlm.nih.gov]

• Gowers Sign

  Gowers sign MedGen UID: 108389 • Concept ID: C0575071 • 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. [ncbi.nlm.nih.gov]

  Lower limb pain and amyotrophy may be present, as well as various cerebellar signs, including dysarthria, nystagmus, hypometric saccades and tremor. [mendelian.co]

• Mental Deterioration

  Other signs involving the central nervous system include mental deterioration, recurrent migraine with "cerebral" vomiting, focal or generalized epilepsy and neurosensory deafness. [mitopedia.org]

  Growth retardation, delayed sexual maturation, and mental deterioration occur in some patients. Older patients have a sensorineural hearing deficit as well. EEG abnormalities are often present. [disorders.eyes.arizona.edu]

  J Neurol Sci 1996 Apr;137(1):20-7 Abstract quote We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. [thedoctorsdoctor.com]

Treatment Treatment Options: No effective treatment is available. [disorders.eyes.arizona.edu]

Separate treatment options for associated disorders (e.g., diabetes mellitus or hypoparathyroidism) may be necessary. In some cases, treatment may include hormone replacement therapies. [rarediseases.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]

In acquired myopathies, treatment is targeted toward the underlying cause. Treatment of statin myopathies is dependent on creatine phosphokinase levels and degree of muscle symptoms. Consider lower doses when initiating statin therapy. [clevelandclinicmeded.com]

Only through understanding the mechanisms of a disease can we begin to plan effective treatments. [mitochondrialdisease.nhs.uk]

Meet other parents and patients in our closed Facebook group. back to top What is the Prognosis for Someone? The prognosis is variable. Some people live a normal life and are minimally affected; others can be severely compromised with the disease. [mitoaction.org]

The prognosis for MELAS is poor. Typically, the age of death is between 10 to 35 years, although some patients may live longer. [umdf.org]

PROGNOSIS Prognosis depends upon which disorder, which symptoms and the severity of those symptoms. Some of the conditions we thought were uniformly progressive and fatal are not (Leigh syndrome, for example). [childneurologyfoundation.org]

Prognosis The prognosis of progressive external ophthalmoplegia depends on the associated neurological problems; in particular, whether there is severe limb weakness or cerebellar symptoms that may be mild or disabling. [medical-dictionary.thefreedictionary.com]

The MTTL1 gene is most often associated with the mitochondrial inheritance pattern, along with other mtRNA and mtDNA genes. [14] Prognosis The prognosis is guarded with a generally progressive disorder. [emedicine.medscape.com]

Rhabdomyolysis may also be seen with infectious etiologies, alcohol, and toxic exposures. [clevelandclinicmeded.com]

While the etiology of multiple deletions is indeterminate and requires nuclear genes analysis, mtDNA deletions accompanying pathogenic point mutations, independently from patient's age, may contribute to the phenotypic severity. [neurology.org]

Etiology Neurol Sci 2014 Mar;35(3):443-8. Epub 2013 Oct 4 doi: 10.1007/s10072-013-1557-8. [ncbi.nlm.nih.gov]

Etiology Kearns-Sayre syndrome is a genetic disorder most commonly due to single sporadic deletions in mitochondrial DNA. [eyewiki.aao.org]

In our national mitochondrial diagnostic reference service, we have been referred several HIV-infected patients with neuromuscular symptoms where a mitochondrial etiology was suspected clinically, and investigations confirmed the presence of a mitochondrial [jamanetwork.com]

The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 2000 ; 48 : 188 –93. ↵ Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. [jmg.bmj.com]

[…] hepatitis B or hepatitis C Reye syndrome Wilson disease Myopathy Chronic demyelinating inflammatory polyneuropathy Dermatomyositis Guillain-Barré syndrome Paraneoplastic syndrome Lactic acidosis Inborn errors of metabolism Polymyositis Sepsis Background Epidemiology [arupconsult.com]

Molecular epidemiologic study of mitochondrial DNA mutations in patients with mitochondrial diseases in Taiwan. Pang CY, Huang CC, Yen MY, Wang EK, Kao KP, Chen SS, Wei YH. [thedoctorsdoctor.com]

The balance of oxidative demands of a given tissue and the proportion of deleted mtDNA it contains will ultimately determine whether the tissue is affected clinically. [12] Epidemiology Frequency Worldwide Worldwide, the prevalence of mitochondrial disease [emedicine.medscape.com]

Table 1 Clinical Features of Common Myopathies Myopathy Epidemiology Distribution of Weakness Other Systemic Manifestations Acquired Myopathies Dermatomyositis Female > male Peak incidence: children and ages 40–60 yr Symmetrical proximal muscle weakness [clevelandclinicmeded.com]

[…] variant Females with heteroplasmy but no clinical symptoms may have affected offspring Variable amount of affected mitochondria is passed to offspring Poor genotype/phenotype correlation exists; the same variant may cause different clinical syndromes Pathophysiology [arupconsult.com]

Pathophysiology Mitochondrial DNA (mtDNA) encodes for essential components of the respiratory chain. [emedicine.medscape.com]

Retinal evaluation reveals disruption and atrophy of retinal photoreceptors as well as aberrant pigment distribution in all layers of the retina. 4, 5 Spongiform degeneration of the brain has been reported in multiple patients at autopsy. 6 Pathophysiology [eyewiki.aao.org]

Endocrine system Endocrine disorders may present in childhood or may develop over time and present in adulthood.[ 17,18 ] Diabetes mellitus with a complex pathophysiology can occur. [bcmj.org]

Back to Top Pathophysiology Disruption of the structural integrity and metabolic processes of muscle cells can result from genetic abnormalities, toxins, inflammation, infection, and hormonal and electrolyte imbalances. [clevelandclinicmeded.com]

Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. [ghr.nlm.nih.gov]

Can Alper's be prevented? If the genetic faults are present, then there is nothing that can be taken during pregnancy or given to the infant that will prevent Alper's occurring. [mitochondrialdisease.nhs.uk]

Prevention There is no way to prevent ophthalmoplegia. Resources Organizations American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. http://www.aan.com. [medical-dictionary.thefreedictionary.com]

Prevention of secondary complications: Antioxidants may ameliorate damage from reactive oxygen species; percutaneous endoscopic gastrostomy may improve nutritional intake and prevent aspiration pneumonia in individuals with severe dysphagia. [ncbi.nlm.nih.gov]

How can mitochondrial disorders be prevented? Since this is a genetically determined disorder, there is no prevention. Prevention of stressors that exacerbate the condition, such as illness, is advocated for all mitochondrial disease. [clinicaladvisor.com]