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Case Studies

As electrons are received and passed down the transport chain, the electron carriers are first reduced with the acceptance of the electron and then oxidized with loss of the electron. A patient poisoned by which of the following compounds has the most highly reduced state of most of the respiratory chain carriers?

A. Antimycin A

B. Rotenone

C. Carbon monoxide

D. Puromycin

E. Chloramphenicol

The right answer is (c) – Carbon monoxide.

Basic concept

The electron transport chain contains three proton pumps linked by two mobile electron carriers. At each of these three sites (NADH-Q reductase, cytochrome c reductase and cytochrome oxidase); the transfer of electrons down the chain powers the pumping of the protons across the inner mitochondrial membrane (figure). As electrons pass through complexes I, III, and IV, protons are pumped across the inner membrane from the matrix to the intermembrane space. This sets up an electrochemical gradient consisting of a proton gradient (chemical), and a membrane potential (because the proton carries a positive charge). The electrochemical gradient represents a form of stored energy derived from the oxidation of NADH (or succinate). A physically distinct complex (ATP synthase or complex V) at a separate location in the inner membrane can exploit the electrochemical gradient to carry out the endergonic ATP synthesis (by oxidative phosphorylation).

 Inhibition of electron transport chain

The blockage of electron transfers by specific point inhibitors leads to a buildup of highly reduced carriers behind the block because of the inability to transfer electrons across the block.

Antimycin A blocks the complex III, Rotenone blocks complex I and Carbon monoxide (As well as cyanide, azide, hydrogen sulfide) block complex IV. Therefore a carbon monoxide inhibition leads to a highly reduced state of all the carriers of the chain. Puromycin and Chloramphenicol are inhibitors of protein synthesis and have no direct effect upon the electron transport chain.

 ETC

Figure-1- Flow of electrons in the electron transport chain and the oxidative phosphorylation

 

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An unskilled worker in a water garden was sent to sweep up a spill of a white powder in the storage shed. Later he was found with labored breathing and convulsions. On further examination, the white powder was identified as rotenone. Respiratory distress is induced on rotenone exposure because it inhibits the complex that catalyzes which of the following?

A. Electron transfer from NADH to coenzyme Q

B. Oxidation of coenzyme Q

C. Reduction of cytochrome c

D. Electron transfer from cytochrome c to cytochrome a1/a3

E. Electron transfer from cytochrome a1/a3 to oxygen

 

The right answer is A) – Electron transfer from NADH to coenzyme Q

Components of Electron Transport Chain- Electrons flow through the respiratory chain through a redox span of 1.1V from NAD+/NADH to O2/2H2O, passing through four large protein complexes;

i) NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (also called Ubiquinone);

ii) Succinate Q reductase (Complex II)-Some substrates with more positive redox potentials than NAD+/NADH (e.g., succinate) pass electrons to Q via succinate Q reductase (Complex II), rather than Complex I.

iii) Q-cytochrome c oxidoreductase (Complex III), which passes the electrons on to cytochrome c; and

iv) Cytochrome c oxidase (Complex IV), which completes the chain, passing the electrons to O2 and causing it to be reduced to H2O (Figure-1).

Mobile complexes

The four complexes are embedded in the inner mitochondrial membrane, but Q and cytochrome c are mobile. Q diffuses rapidly within the membrane, while cytochrome c is a soluble protein.

 ETC

Figure-1- Components of electron transport chain. The three complexes I, III and IV acts as proton pumps, ATP is synthesized when protons flow back to the mitochondrial matrix through ATP synthase complex.

Flavoproteins (are important components of Complexes I and II. The oxidized flavin nucleotide (FMN or FAD) can be reduced in reactions involving the transfer of two electrons (to form FMNH2 or FADH2), but they can also accept one electron to form the semiquinone. Iron-sulfur proteins (non-heme iron proteins, Fe-S) are found in Complexes I, II, and III. These may contain one, two, or four Fe atoms linked to inorganic sulfur atoms and/or via cysteine-SH groups to the protein. The Fe-S takes part in single electron transfer reactions in which one Fe atom undergoes oxidoreduction between Fe2+ and Fe3+.

Electron flow in ETC (figure-2)

NADH-Q oxidoreductase or Complex I is a large L-shaped multi-subunit protein that catalyzes electron transfer from NADH to Q, coupled with the transfer of four H+across the membrane: Electrons are transferred from NADH to FMN initially, then to a series of Fe-S centers, and finally to Q (Figure-2). In Complex II (succinate -Q reductase), FADH2 is formed during the conversion of succinate to fumarate in the citric acid cycle and electrons are then passed via several Fe-S centres to Q.

Coenzyme Q or Ubiquinone (ubi). Ubi accepts electrons and transports them to Complex III. Ubi is capable of moving in the membrane between Complex I and III, picking up electrons at Complex I and dropping them off at Complex III. As is the case with Complex I, Complex III contains a series of proteins that transport electrons. The electrons are removed from Complex III by a small peripheral membrane protein known as cytochrome c. Cytochrome c transports the electrons from Complex III to Complex IV.

Reduced cytochrome c is oxidized by Complex IV (cytochrome c oxidase).

This transfer of four electrons from cytochrome c to O2 involves two heme groups, a and a3, and Cu. 

Complex IV finally gives its electrons to molecular oxygen (O2), the final or terminal electron acceptor. The reduction of oxygen results in the formation of a water molecule from the oxygen.

 

 Flow of electrons

Figure-2- Flow of electrons in the electron transport chain

Site specific inhibitors -Specific inhibitors of electron transport for example, rotenone and amobarbital block electron transfer in NADH-Q oxidoreductase and thereby prevent the utilization of NADH as a substrate. The central portion of the rotenone structure resembles the isoalloxazine ring of the FMN molecule, and when it binds to complex I, rotenone prevents the transfer of electrons from NADH to coenzyme Q. In contrast, electron flow resulting from the oxidation of succinate is unimpaired, because these electrons enter through QH2, beyond the block. Malonate is a competitive inhibitor of Complex II

BAL (British Anti Lewisite), Antimycin A interferes with electron flow from cytochrome b in Q-cytochrome c oxidoreductase.

Furthermore, electron flow in cytochrome c oxidase can be blocked by cyanide (CN-), azide (N3 -), and carbon monoxide (CO). Cyanide and azide react with the ferric form of heme a 3, whereas carbon monoxide inhibits the ferrous form. Inhibition of the electron-transport chain also inhibits ATP synthesis because the proton-motive force can no longer be generated.

 

 

 

 

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An -8 year-old boy is seen by an ophthalmologist for difficulties in seeing in all visual fields as well as slow eye movements. The ophthalmologist finds pigmentary retinopathy and ophthalmoplegia. The child is suspected to have Kearns- Sayre syndrome, a disorder due to a mutation in complex II of ETC. The electron transport from which substance would be impaired?

A. Malate

B. Isocitrate

C. Succinate

D. Pyruvate

E. Alpha Keto glutarate

Answer- The correct answer is C- Succinate.

Electrons flow through the respiratory chain through a redox span of 1.1 V from NAD+/NADH to O2/2H2O passing through three large protein complexes;

1) NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (Q) (also called ubiquinone)

2) Q-cytochrome c oxidoreductase (Complex III), which passes the electrons on to cytochrome c; and

3) Cytochrome c oxidase (Complex IV), which completes the chain, passing the electrons to O2 and causing it to be reduced to H2O .

Some substrates with more positive redox potentials than NAD+/NADH (e.g., succinate) pass electrons to Q via, succinate Q reductase (Complex II), rather than Complex I.

The four complexes are embedded in the inner mitochondrial membrane, but Q and cytochrome c are mobile. Q diffuses rapidly within the membrane, while Cytochrome c is a soluble protein.

ETC

Figure- Flow of electrons through the respiratory chain complexes.

Malate, Isocitrate and alpha ketoglutarate are intermediates of TCA cycle, the electrons flow from them to NAD+ forming NADH that is regenerated back to its oxidized form by passing electrons to complex I of ETC. Similarly electron flow from Pyruvate is also through complex I.

Electron from Succinate pass to FAD forming FADH2 that is regenerated back to its oxidized form after passing its electrons to complex II of ETC.

Thus the correct answer for the given problem is Succinate.

 

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An 18-year-old college student is brought to the emergency room unconscious, with a very high serum alcohol level. Alcohol metabolism can result in high NADH levels. When NADH enters the electron transport chain, which of the following is the correct order in which electron transfer occurs ?

a) NADH, coenzyme Q, cytochrome c, FMN,O2

b) NADH, cytochrome c, coenzyme Q, FMN,O2

c) NADH, FMN, coenzyme Q, cytochrome c, O2

d) NADH, cytochrome c, FMN, cytochrome c, O2

e) NADH, FMN, cytochrome c, coenzyme Q, O2

 

The right answer is (c).The electron flow is from NADH to O2 passing through FMN, coenzyme Q (ubiquinone) and cytochrome c (Figure-1). See the details below-

 

Overview of ETC

 Figure-1  – An overview of Electron transport chain . FeS represents iron sulfur center, and cytochrome b,c1 are components of complex III.

Basic concept of electron transport chain

Introduction-Most of the energy liberated during the oxidation of carbohydrates, fatty acids, and amino acids is made available within mitochondria as reducing equivalents (—H or electrons) .The NADH and FADH2 formed in glycolysis, fatty acid oxidation, and the citric acid cycle are energy-rich molecules because each contains a pair of electrons having a high transfer potential. The enzymes of the citric acid cycle and β-oxidation are contained in mitochondria, together with the respiratory chain (electron transport chain), which collects and transports reducing equivalents, directing them to their final reaction with oxygen to form water (Figure-2)

Role of ETC in ATP formation

 Figure-2- The energy trapped in the food is passed on to electron transport chain after a series of oxidative processes, in the form of reducing equivalents, where finally energy is released as ATP

Components of Electron Transport Chain

Electrons flow through the respiratory chain through a redox span of 1.1V from NAD+/NADH to O2/2H2O, passing through three large protein complexes (Figure-3)

1) NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (Q) (also called Ubiquinone);

2) Q-cytochrome c oxidoreductase (Complex III), which passes the electrons on to cytochrome c; and

3) Cytochrome c oxidase (Complex IV) ,which completes the chain, passing the electrons to Oand causing it to be reduced to H2O (Figure-1).

4) Succinate Q reductase (Complex II),Some substrates with more positive redox potentials than NAD+/NADH (eg, succinate) pass electrons to Q via a fourth complex, succinate Q reductase (Complex II), rather than Complex I.

The four complexes are embedded in the inner mitochondrial membrane, but Q and cytochrome c are mobile. Q diffuses rapidly within the membrane, while cytochrome c is a soluble protein.

 

Components of ETC

 Figure-3- Showing the components of electron transport chain. Arrows show the flow of protons.

Electron flow in ETC 

NADH-Q oxidoreductase or Complex I is a large L-shaped multi-subunit protein that catalyzes electron transfer from NADH to Q, coupled with the transfer of  four H+across the membrane: Electrons are transferred from NADH to FMN initially, then to a series of Fe-S centers, and finally to Q (Figure-4).

NADH dehydrogenase complex

 Figure-4NADH-Q oxidoreductase is a large L-shaped multi-subunit protein that catalyzes electron transfer from NADH to Q, coupled with the transfer of  four H+across the membrane

In Complex II (succinate -Q reductase), FADH2 is formed during the conversion of succinate to fumarate in the citric acid cycle and electrons are then passed via several Fe-S centres to Q (Figure-3 and 5).

Flow of electrons in ETC

Figure-5- Showing the flow of electrons through four complexes. Coenzyme Q and cytochrome c are mobile carriers. Complex V is ATP synthase complex, meant for ATP production.

Iron-sulfur proteins (non-heme iron proteins, Fe-S) are found in Complexes I, II, and III (Figure-5).These may contain one, two, or four Fe atoms linked to inorganic sulfur atoms and/or via cysteine-SH groups to the protein (Figure-6). The Fe-S takes part in single electron transfer reactions in which one Fe atom undergoes oxidoreduction between Fe2+ and Fe3+.

 

Iron -sulphur centers

Figure-6- Iron sulfur proteins (Fe-S). (A) The simplest Fe-S with one Fe bound by four cysteines. (B) 2Fe-2S center. (C) 4Fe-4S center.

Flavoproteins (are important components of Complexes I and II (Figure-4). The oxidized flavin nucleotide (FMN or FAD) can be reduced in reactions involving the transfer of two electrons (to form FMNH2 or FADH2),but they can also accept one electron to form the semiquinone.

Coenzyme Q or Ubiquinone (ubi). Ubi accepts electrons and transports them to Complex III. Ubi is capable of moving in the membrane between Complex I and III, picking up electrons at Complex I and dropping them off at Complex III (Figure-3 and 5).

As is the case with Complex I, Complex III contains a series of proteins that transport electrons. As the electrons are moved from carrier to carrier within Complex III, the energy that is released moves hydrogen ions out of the mitochondrion (Figure-3).Thus, Complex III also serves as a hydrogen ion pump. Once again, there must be a mechanism by which electrons are removed from Complex III. This done by a small peripheral membrane protein known as cytochrome c. Cytochrome c transports the electrons from Complex III to Complex IV.

Reduced cytochrome c is oxidized by Complex IV (cytochrome c oxidase), with the concomitant reduction of O2 to two molecules of water(Figure-3 and 4).

This transfer of four electrons from cytochrome c to O2 involves two heme groups, a and a3,and Cu. Electrons are passed initially to a Cu centre (CuA), which contains 2 Cu atoms linked to two protein cysteine-SH groups (resembling an Fe-S), then in sequence to heme a, heme a3, a second Cu centre, CuB, which is linked to heme a3, and finally to O2.

By the time the electrons reach the final electron acceptor in Complex IV, they have very little energy left . Complex IV finally gives its electrons to molecular oxygen (O2), the final or terminal electron acceptor. The reduction of oxygen results in the formation of a water molecule from the oxygen (Figure-3 and 5).

For every pair of electrons donated to the ETC by an NADH, ½ O2(or one O atom) is reduced to form one water molecule. Two NADH’s would result in the use of 1 (½ + ½) O2 molecule, and so on. If there was no oxygen to take the electrons from Complex IV, the electrons would accumulate up the electron transport chain very quickly and NADH would no longer be able to donate electrons to the ETC (because the ETC would be filled with electrons).This would cause an accumulation of NADH and a shortage of NAD+(remember, NAD+ is regenerated when NADH donates its electrons to Complex I). Without NAD+, there would be no electron acceptors for the Krebs Cycle and all reactions that require NAD+ would stop. This would cause the entire Krebs Cycle to stop. Thus the Krebs Cycle would not run if there were no oxygen present, thus it is considered aerobic!

Proton Motive Force -The flow of electrons from NADH or FADH2 to O2 through protein complexes located in the mitochondrial inner membrane leads to the pumping of protons out of the mitochondrial matrix.(Figure-3) .The resulting uneven distribution of protons generates a pH gradient and a transmembrane electrical potential that creates a proton-motive force (Figure -7). ATP is synthesized when protons flow back to the mitochondrial matrix through an enzyme complex (Figure -3 and 4). Thus, the oxidation of fuels and the phosphorylation of ADP are coupled by a proton gradient across the inner mitochondrial membrane.

Proton motive force

 Figure-7-showing the electrochemical gradient created by pumping of protons across the inner mitochondrial membrane

In other words, the electron-motive force is converted into a proton-motive force and, finally, the proton-motive force is converted into phosphoryl transfer potential.

Like NADH, FADH2 contains electrons (and energy) from oxidation reactions. FADH2, however, contains less energy than does NADH. Because of this, FADH2 is unable to donate its electrons to Complex I of the ETC. Instead, FADH2 donates its electrons to Complex II. Complex II eventually passes the electrons on to Complex III via Ubiquinone. From then on, the electrons follow the same pathway as do those from NADH. Complex II, it turns out, does not move protons as the electrons are transported. This means that every NADH that donates electrons to the ETC will cause more hydrogen ions to be transferred than does each FADH2.

Oxidative phosphorylation- The reduction of molecular oxygen to water yields a large amount of free energy that can be used to generate ATP. Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms.

P: O ratio

There is a net direct capture of two high-energy phosphate groups in the glycolytic reactions. Two more high-energy phosphates per mole of glucose are captured in the citric acid cycle during the conversion of Succinyl CoA to succinate. All of these phosphorylation occur at the substrate level. When substrates are oxidized via Complexes I, III, and IV in the respiratory chain (i.e., via NADH), 3 mol of ATP are formed per half mol of O2 consumed; ie, the P:O ratio = 3. On the other hand, when a substrate (e.g. succinate) via FADH2 is oxidized through Complexes II, III, and IV, only 2 mol of ATP are formed; i.e., P:O =2. These reactions are known as oxidative phosphorylation at the respiratory chain level. Taking these values into account, it can be estimated that nearly 90% of the high energy phosphates produced from the complete oxidation of 1 mol glucose is obtained via oxidative phosphorylation coupled to the respiratory chain.

To be continued……

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Case Study

An elderly couple was brought by ambulance to the emergency department after their daughter noticed that they were both acting “strangely.” The couple had been in good health prior to the weekend. Their daughter had gone out to spend the week-end with her friends.

The couple had been snowed in at their house until the snowplows cleared the roads. They had plenty of food and were kept warm by a furnace and blankets. On reaching home after two days, their daughter noticed that they both were complaining of bad headaches, confusion, fatigue, and some nausea.

On arrival to the emergency department, both patients were afebrile with normal vital signs and O2 saturation of 99 percent on 2 L of O2 by nasal cannula. Their lips appeared to be very red. Both patients were slightly confused but otherwise oriented. The physical examinations were within normal limits. Carboxyhemoglobin levels were drawn and were elevated.

What is the most likely cause of these patients’ symptoms?

Case details

The elderly couple is most probably suffering from CO poisoning. The cause might be the accidental exposure to CO by the burning of the furnace in the closed room. The symptoms, of headache, confusion, fatigue, nausea and red lips are suggestive of CO poisoning. Since the level of carboxy hemoglobin is also high, so the diagnosis is confirmed that the couple is suffering from CO poisoning.

Carbon monoxide (CO) poisoning, one of the most common fatal poisonings, occurs by inhalation. Carbon monoxide is a colorless, odorless gas produced by the combustion of carbon-containing materials. Poisoning may occur as a result of suicidal or accidental exposure to automobile exhaust, smoke inhalation in a fire, or accidental exposure to an improperly vented gas heater or other appliance. Inhaling tobacco smoke results in CO in the blood but not enough to cause poisoning. 

Mechanisms of CO toxicity are not completely understood. They appear to involve the following

1)   Carbon monoxide avidly binds to hemoglobin, with an affinity approximately 250 times that of oxygen. This results in displacement of O2 from Hb resulting in reduced oxygen-carrying capacity and altered delivery of oxygen to cells.

2)   Binding of CO to hemoglobin causes an increased binding of oxygen molecules at the 3 other oxygen-binding sites, resulting in a leftward shift in the oxyhemoglobin dissociation curve and decreasing the availability of oxygen to the already hypoxic tissues.

3)   Inhibition of mitochondrial electron transport chain

4)   Possibly direct toxic effects on brain tissue

CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery.

The transfer of Oto enzymes requiring O2 is also inhibited. Several different sites within the body get affected but its most profound impact is on the organs (eg, brain, heart) with the highest oxygen requirement. Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination.

 Inhibition of Electron Transport Chain

CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO disrupts the O2-dependent step of the electron transport chain, leading to unavailability of ATP. In the electron transport chain, only complex IV (cytochrome oxidase) interacts directly with O2. As with hemoglobin, CO has a higher affinity for cytochrome oxidase than O2. Thus CO binds tightly to cytochrome oxidase and inhibits the binding of O2  This results in inhibition of electron transport chain with the resultant inhibition of  phosphorylation of adenosine diphosphate (ADP), to form adenosine triphosphate (ATP). This becomes more profound as additional molecules of cytochrome oxidase are bound by CO. 

Clinical symptoms- Symptoms tend to correlate well with the patient’s peak blood carboxy hemoglobin levels. Many symptoms are nonspecific.

  • Headache and nausea can begin when levels are 10 to 20%.
  • Levels > 20% commonly cause vague dizziness, generalized weakness, difficulty concentrating, and impaired judgment.
  • Levels > 30% commonly cause dyspnea during exertion, chest pain (in patients with coronary artery disease), and confusion.
  • Higher levels can cause syncope and  seizures,
  • Hypotension, coma, respiratory failure, and death may occur, usually when levels are > 60%.

Management- The binding of CO to hemoglobin is fully dissociable, and dissociation requires ventilation. Patients should be removed from the source of CO and stabilized as necessary. They are given 100% Oand treated supportively.

 Utilization of 100 percent O2 accelerates the washout of CO. Use of hyperbaric chambers with pressures up to 2 atmospheres speeds up the CO washout process even more. Addition of 5 to 7 percent CO2 to the O2 is sometimes used as a prompt to ventilatory exchange.

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Case Study

A 30 -year- old patient reported to medical OPD complaining of generalized weakness, excessive perspiration, and high caloric intake without increase in body weight. From the age of seven she had suffered from profuse sweating that forced her to change clothes about ten times a day. To compensate for the loss of fluids she had to drink many liters of water every day. Her calorie intake was about 3500 calories a day, approximately the need for a manual laborer, despite a body weight of only 40 kilograms.

There was no sign of any other disease. The BMR of the patient was excessively elevated but the thyroid hormones (T3 and T4) were in normal concentrations. Laboratory tests showed small deviations from the normal picture, with the exception of her blood volume, which was about twice as large as normal.

What is the probable diagnosis?

Case details The patient is probably suffering from Luft’s syndrome, also called Hypermetabolic mitochondrial syndrome.  

All the symptoms like high caloric intake but failure to gain weight, excessive perspiration, excessive thirst etc indicate a state of severe hyper metabolism of non thyroid origin (since thyroid hormones -T3 and T4 are normal). The defect lies in the maintenance of mitochondrial respiratory control.

Mitochondria play a major role in human energy dynamics (ATP synthesis and related reactions), and a functional deficit may be expected to result in diminished supply of high energy phosphate bonds. In mitochondria, electron transfer is coupled to oxidative phosphorylation via a proton gradient, and the energy released from oxidation is transferred to the ATP synthase trapping system. A class of compounds called uncouplers can block electron-transfer- linked phosphorylation at any of the three stages (energy production, transfer, or trapping). Redox reactions release free energy (delta G negative), such energy may be dissipated as heat, or be trapped as a proton gradient. Whether energy is dissipated or trapped depends on the characteristics of biologic membranes rather than on the reaction itself. Any substance that allows protons to leak across membranes will play an uncoupling role, since it will block the transfer of energy between electron flow and ATP synthesis.

More than 90% of the oxygen used in the human body is utilized by mitochondrial cytochrome oxidase, which transfers four electrons into an oxygen molecule to produce two molecules of water.

Deficits in mitochondrial function arise by two mechanisms: (1) a block in electron flow or ATP synthesis which results in lactic acidosis; and (2)uncoupling electron flow from ATP synthesis (Luft syndrome) in which oxidation occurs at a rapid rate but without a concomitant increase in ATP synthesis (energy released is dissipated as heat).

In Luft syndrome the uncoupling is caused by abnormality in the mitochondrial membrane. Electron transport is only loosely coupled to ATP production, thus the extra energy evolves in the form of heat.

Thus this syndrome is characterized by

·       Severe hyper metabolism,

·       Heat intolerance,

·       Profuse perspiration,

·       Polyphaga,

·       Polydipsia without polyuria,

·      Muscular wasting and weakness,

·      Absent deep reflexes, and

·      Resting tachycardia.

·   At the cellular level, the mitochondria respire wildly and waste the excess energy as heat, elevation of body temperature up to 38.4 °C.

·     There is progressive weight loss despite increased food intake.

·     Thyroid function is normal.

·      Onset is in childhood.

·     The rise in BMR is due to partial uncoupling of oxidative phosphorylation. Since there is less ATP production and the extra energy is lost in the form of heat , all the metabolic processes are stimulated. Due to high BMR only there is failure to put on weight despite a good diet.

Laboratory Investigations

Routine investigations can be undertaken for differential diagnosis. BMR, Thyroid function tests , blood glucose etc can be measured to rule out the presence of other conditions with similar symptoms.

Treatment

There is no permanent cure for this disease. Symptomatic treatment can only be given. Vitamin therapy in the form of Vitamins C, K, and E, along with coenzyme Q10 and a high-caloric diet is recommended.   Protection from heat is advised.

 

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