Mitochondrial Disease - Clinical Presentation’s, Symptoms & Treatment Considerations
Alpers Disease
Symptoms: Seizures, dementia, spasticity, blindness, liver dysfunction and cerebral. Degeneration.
Barth Syndrome
Symptoms: Skeletal myopathy, cardiomyopathy, short stature and neuropenia.
Beta-Oxidation Defects
LCAD, LCHAD, MAD, MCAD, SCAD, SCHAD, VLCAD
Treatment: High carbohydrate-low fat diet, administration of medium-chain triglyceride oil and diet supplementation with carnitine and / or riboflavin. Avoidance of fasting.
SPECIAL NOTE: Information about all Mitochondrial Treatments Listed is very general and for information purposes only. No treatment should be considered or implemented without first speaking with your GP and or your Child’s Consultant.
Carnitine-Acyl-Carnitine Deficiency
Symptoms: Siezures, apnea, bradycardia, vomiting, lethargy, coma, enlarged liver, limb weakness, myoglobin in the urine, Reye-like symptoms triggered by fasting.
Carnitine Deficiency
Symptoms: Cardiomyopathy, failure to thrive, and altered consciousness or coma, sometimes hypotonia.
Treatment: Diet Supplementation with L-Carnitine
Co-Enzyme Q10 Deficiency
Symptoms: Encephalomyopathy, mental retardation, exercise intolerance, ragged-red fibres, and recurrent myoglobin in the urine.
Treatment: Administration of Co-Enzyme Q10
Complex I Deficiency
Symptoms: There are three forms:
1.Fatal infantile multisystem disorder characterised by development delay, muscle weakness, heart disease, congenital lactic acidosis, and respiratory failure.
2.Myopathy beginning in childhood or in adult life, manifesting as exercise intolerance or weakness. Elevated lactate common.
3.Mitochondrial encephalomyopathy, (including MELAS), which may begin in childhood or adult life and consists of variable combinations of symptoms and signs, including ophthalmoplegia, seizures, dementia, ataxia, hearing loss, pigmentary retinopathy, sensory neuropathy, and uncontrollable movements. May cause Leigh Syndrome.
Treatment: Administration of thiamine, riboflavin, biotin, carnitine, co-enzyme Q10, and ketogenic diet has been successful in some cases, but not in the infantile multisystem syndrome.
Complex II Deficiency
Symptoms: Encephalomyopathy and various manifestations, including failure to thrive, development delay, hypotonia, lethargy, respiratory failure, ataxia, myoclonus. Lactic acidosis common. May cause Leigh Syndrome.
Complex III Deficiency
Symptoms: Four major forms:
1.Fatal infantile encephalomyopathy, congenital lactic acidosis, hypotonia, dystrophic posturing, and coma. Ragged-red fibres common
2.Encephalomyopathies of later onset (childhood to adult life): various combinations of weakness, short stature, ataxia, dementia, haring loss, sensory neuropathy, pigmentary retinopathy, and pyramidal signs. Ragged-red fibres common. Possible lactic acidosis.
3.Myopathy, with exercise intolerance evolving into fixed weakness. Ragged-red fibres common. Possible lactic acidosis.
4.Infantile histiocyoid cardiomyopathy.
Complex IV Deficiency / COX Deficiency
Symptoms: Two Major Forms
1.Encephalomyopathy: Typically normal for the first 6 to 12 months of life and show development progression, ataxia, lactic acidosis, optic atrophy, ophthalmoplegia, nystagmus, pyramidal signs, and respiratory problems. Frequent seizures. May Cause Leigh Syndrome.
2.Myopathy: Two Main Variants:
a)Fatal infantile myopathy: may begin soon after birth and accompanied by hypotonia, weakness, lactic acidosis, ragged-red fibres, respiratory failure, and kidney problems.
b)Bengin infantile myopathy; may begin soon after birth and accompanied by hypotonia, weakness, lactic acidosis, ragged-red fibres, respiratory problems, but(if the child survives) followed by spontaneous improvemet.
Complex V Deficiency
Symptoms: Slow, progressive myopathy
CPEO
Symptoms: Similar to those of KSS plus: visual myopathy, retinitis pigmentosa, and dysfunction of the central nervous system.
CPT I Deficiency
Symptoms: Enlarged liver and recurrent Reye-like episodes triggered by fasting or illnesses.
Treatment: Medium-chain triglycerides
CPT II Deficiency
Symptoms - Myopathic: Exercise intolerance, fasting intolerance, muscle pain, muscle stiffness, and myoglobin and in the urine.
Symptoms – Infantile: Reye-like syndrome, enlarged liver, hyopglycemia, enlarged heart, and cardiac arrhythmia.
KSS
Symptoms: Progressive external ophthalmoplegia, pigmentary retinopathy, heart block, and high cerebrospinal protein.
Lactic Acidosis
Treatment: See Prof. Hass & Prof. Stackpoole - Dichloroacetate (DCA) Clinical Trail Update at the United Mitochondrial Disease Foundation Web Site www.umdf.org
LCAD, LCHAD, MAD, MCAD, SCAD, SCHAD, VLCAD
Treatment & Full Symptoms: Please visit the Fatty Oxidation Support Group at www.fod.org
Leigh Disease or Syndrome
Symptoms: Seizures, hypotonia, fatigue, nystagmus, poor reflexes, eating and swallowing difficulties, breathing problems, poor motor function, lactic acidosis, ataxia.
LHON
Symptoms: Primary blindness in young men. Less common symptoms: mild dementia, ataxia, spasticity, peripheral neuropathy, and heart conduction defects.
Luft Disease
Symptoms: Hypermetabolism, with fever, heat intolerance, profuse respiration, polyphagia, polodispia, ragged-red fibres, and resting tachycardia. Exercise intolerance with mild weakness.
MELAS
Symptoms: Short stature, seizures, stroke-like episodes with focused neurological deficits, recurrent headaches, cognitive regression, disease progression, ragged-red fibres, and lactic acidosis.
MERRF
Symptoms: Myoclonus, epilepsy, progressive ataxia, muscle weakness and degeneration, deafness and dementia.
Mitochondrial Cytopathy
General classification for Mitochondrial Diseases. All diseases listed here are Mitochondrial Cytopathies.
Mitochondrial DNA Depletion, Deletion & Point Mutation Syndromes
Symptoms: Three Forms
1.Congenital myopathy: Neonatal weakness, hypotonia requiring assisted ventilation, possible renal dysfunction. Severe lactic acidosis. Prominent ragged-red fibres. Death due to respiratory failure occurs before one year of age.
2.Infantile myopathy: Following normal early development until one year old, weakness appears and worsens rapidly, causing respiratory failure and death typically within a few years.
3.Hepatopathy: Enlarged liver and intractable liver failure, myopathy. Severe lactic acidosis. Death is typically within the first year.
MINGIE
Symptoms: Progressive external ophthalmoplegia, limb weakness, peripheral neuropathy, digestive tract disorders, leukodystrophy, lactic acidosis, ragged-red fibres.
NARP
Symptoms: Neuropathy, Ataxia & Retintis Pigmentosa, The condition has been know to present itself with non-neurological developments and involvements and symptoms.
Cause: Mitochondrial DNA point mutation’s in genes associated with Complex V: T8993G & T8993C. Leigh syndrome may develop in some cases.
Pearson Syndrome
Symptoms: Bone marrow and pancreas dysfunction
Pyruvate Carboxylase Deficiency
Symptoms: Lactic acidosis, hypoglycemia, serve retardation, failure to thrive. Common symptoms: Seizures and spasticity.
Pyruvate Dehydrogenase Deficiency
Symptoms: Lactic acidosis, pyruvic acidosis, spinal and cerebellar degeneration. Less common: Agenesis of the corpus collosum and lesions in the basal ganglia, cerebellum, and brain stem. Also: Growth delay, hypotonia, seizures, and polyneuropathy. Sometimes found to be the cause of Leigh disease.
Respiratory Chain Disorders
SEE: Complex I, II, III, IV, V and NARP
Certain parts of this article have been used with permission from the United Mitochondrial Disease Foundation. www.umdf.org
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