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Internship Final Case Leigh’s Syndrome
Name: Fatma S. Mohammed Al N’uaimi ID: 201150304 Preceptor: R.D. Rosario Coordinator: Dr.Habiba
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2INTRODUCTION Definition, pathophysiology, diagnosis, epidemiology, and dietary intervention ..
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Introduction
• Leigh’s Disease is a rare X-linked inherited disease that effects the central nervous system and consider the most sever mitochondrial dysfunction.
• It is neurometabolic, which means it deals with the nerves and metabolism.
• Begins normally in infants between the age of three months and two years.
• Very rarely occurs in teenagers and adults, but is possible.
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
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Etiology
Mutations within the mitochondrial DNA
Deficiencies in pyruvate dehydrogenase enzyme.
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
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Pathophysiology
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
NORMAL CONDITION LEIGH’S SYNDROME
No ATPATP
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Signs and Symptoms
Motorcycle Skills
loss of sucking ability, control of the head, and
motor skills.
Progressed symptoms weakness, loss of muscle, and lactic acidosis which
can later affect the kidneys and lungs.
GI &Neurological
Low appetite,
vomiting, crying, and seizures.
Lactic acidosis
A condition characterized by the
accumulation of lactic acid in bodily tissues
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
Prognosis• The prognosis for Leigh’s Disease is very poor.
• Those for whom the condition is well progressed die within the first few years.
• Those with only partial deficiencies can live to six to seven years.
• Very few have lived to teenage years.
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
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Treatment
de Lonlay et al. Nature Genetics. 2012Finsterer J et al. pediatrneurol.2008
Vitamin B1Serve as cofactor
Ketogenic DietLow CHO, High fat
-Sodium bicarbonate-Sodium citrate
To help manage the lactic acidosis.
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9SUBJECTIVE All the information obtained verbally form the parents and nurses.
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Date of Visit : October 25, 2016
• Name: M.S.S
• Age:6 years old
• Gender: Female
• Nationality: Emirati
Social Related • Occupation: Nil
• Educational level: Nil
• Economic status: Good economic status.
• Support systems: nil
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Medically Related • Patient Medical History: I interviewed the parents and the following information's were obtained.
-According to the Father: The patient was perfectly healthy until age 2 years with no signs or symptoms; she collapsed and developed asthma. Admitted to TAWAM ICU; she had infection in the tracheostomy, leg and UTI and the MD injected high dose of 3 types of antibiotics ending up with coma.
-The physicians in U.S. informed the parents that she’s clinically died
• Family Medical History: DM, Grandmother.
• Family Genetic history: Nil genetic syndromes in the family or relatives; the genetic test before marriage showed NO possible inherited diseases.
• Medications: before she collapsed nil medications were taken.
• Other practice:
-Father routinely do “ Hijama” for the patient.
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Additional Information • Multidisciplinary team: met the family they discussed with them regarding the harmful
use of herb, juices, milk for possible drug nutrient interaction. In addition bringing external physicians from different healthcare facilities.
• Physiotherapy: according to speech-therapist; the additional session will cause more harm to the condition.
• Pharmacist: Mindlinx multinutrient, Mindlinx Powder and Children's OmegaBerry provided by the father form external center and the products NOT registered in Health Ministry.
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Physical observation /Clinical symptoms
• Unconscious
• Mechanically ventilated
• Excessive Salivations
• Clogging in tube feeding
• Hormonal changes “ Early Puberty”: Enlargement of the breasts and monthly period
• Bowel Motion: passing bowel motion with the help of laxatives “ per nurse report”
• Urine output: passing good amount of yellowish urine“ per nurse report”
• GI: nil vomiting; nil nausea.
Other Information's
• The parents asked to have more physiotherapy sessions in TAWAM hospital.
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Nutrition Related• Recent weight change: According to the parents there’s weight fluctuation
• Food allergies/aversions: No known allergies
• The Father reused to insert PEG tube feeding instead of NGT.
• Dietary habits: the parents insisted to give her honey even with explanation for the harmful use of simple sugar in her condition ” per dietitian report”
• The patient receives camel milk (20ml); orang, beetroot, Apple, and blue berry juices once every alternative day or sometimes once a week in low dose “ per father report’
Enteral Feeding “Current Intake” Route Nasogastric- NGT Method of feeding Intermittent feeding Formula Pediasure Fiber Volume 680ml Flushing water 20 ml pre/post feeding Additional Additives camel milk powder 10ml + 10ml juices
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15OBJECTIVE All the information's obtained from the medical record..
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Personal Information
• Name: K.S.I.
• Age: 6 years old
• Gender: Female
• Religion: Muslim
• Nationality: Emirati
• Social status: single
• Insure card: Daman Thiqa
Resident ID: LTMRH1081
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• Date of admission: December 17th , 2014
• Chief complaints: Leigh’s Disease; Chronic respiratory failure; complex mitochondrial disease; psychomotor retardation; cerebral palsy; cardiomyopathy; GERD; seizure disorder; acute constipations; optic nerve atrophy
• Clinical symptoms: excessive salivation; facial twitching; arm jerking; eye blinking.
• Diagnosis: Leigh’s Disease; Chronic respiratory failure; complex mitochondrial disease; psychomotor retardation; cerebral palsy; cardiomyopathy; GERD; seizure disorder; acute constipations; optic nerve atrophy; MELAS disorder “mitochondrial encephalomyopathy”; Thalassemia.
• Communication: No verbal or functional communications.
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Anthropometric Measurements
On 02.10.2016
Weight (kg): 26.7kg
Height (cm): 123cm
Compared to Ulna Length: 19 cm ( 122 cm)
Wiest Circumferences 21 cm
Weight (kg): 26.7kg
Weight for age(): Above 90th percentile
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Date Weight (Kg)
02.08.2016 25.Kg
02.09.2016 23kg * Due to sickness and low rate feeding
05.09.2016 26.9kg
02.10.2016 26.7kg
Weight Change
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Energy Requirements
Total Energy (kcls) Using Krick Formula *Birth-10 years: [EAR * LPAR*BTR*GRR]* Weight(kg) * : (76)*(0.74)*(0.9)*(0.8)= 40.49 * 26.7kg : 1081 kcal /day NOTE: since the patient is gaining weight due to nature of the disease and with observation giving full caloric need causing the patient to gain more weight; a 48% of total calories will be provided. This intervention was discussed and approved by the physician.
Therefore: (1081 * 0.48) = 518.8 kcal/day
Protein needs (gm) 0.8-1.1g /kg = 0.8-1.1*26.7= 21- 29 g/day
Fluid needs (ml) 1500 + (20*6)= 1620ml
P.S. I contacted with several dietitians specialized in mitochondrial diseases (Queen’s university, New York; King Saud University, KSA; and Tawam Hospital, UAE. The answer was there’s no dietary guidelines for mitochondrial syndromes in general and only vitamin therapy are used to manage the complication of the disease.
* Adapted form nutritional requirements for children in health and disease 2000 London: Great Ormand street Hospital for Children NHS trust.*EAR: Estimated average requirements / LPAR: physical activity ratio/ BTR: bone tone ratio/ GRR: Growth rate ratio
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Current intake
• No Abdominal Distention
• Normal bowel movement with laxatives help.
Current Nutritional and GI status
• Diet History: the patient use to be in cyclic regimen then shifted to intermittent as per father order. The full strength formula cased the patient abdominal distension and blotting. The formula modified to half strength and sing of tolerance improved.
• Enteral feeding via NGT; intermittent with Pediasure Fiber and goal rate of 85ml/hr (42.5 ml) diluted in 42.5 ml Q3 (6,9,12,15,18,21,24,3)
• 20 cc flushing pre/post feeding Q3 (320ml total) • 140 ml for medication + 250ml for Movicol
• 2scoops BeneFiber dissolved in 60ml q8 ( 6,14, 22) (60*3=180 )+ (20ml*3=60 ml flushing) / total= 240ml ) • 3scoops BeneProtein dissolved in 100ml q 24 (20ml flushing + 100ml = 120ml) • 20 ml additives.
• 5 ml to dissolve 5ml (1 teaspoon) Honey.
NAME CLASS USEHyaluronic acid Anionic Used to treat dry eyes.
Ipratropium bromide Antiarrhythmic Used for various bronchial disorders, in rhinitis, and wheezing. Adverse effects can be increased when Ipratropium bromide is combined with Scopolamine.
Scopolamine Anticholinergic Used to prevent nausea and vomiting due to motion sickness
Levetiracetam Anticonvulsant Used for seizures
Calcium Carbonate antacid Used for neutralizing hydrochloric acid in gastric secretions. Subsequent increases in pH may inhibit the action of pepsin Or to treat hypocalcemia.
Esomeprazole Antiacidic A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers
3% Sodium Chloride Salt Used for dehydration.
Movicol Adult Diazepam Laxative Used to relieves constipation
Fluticasone Anti-inflammatory Nasal spray is indicated for the treatment of the symptoms of seasonal and perennial allergic rhinitis in patients aged 2 years and older.
Omega-3 Antioxidant Used in the treatment of anemia. Involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
Multivitamins - Used to correct any deficiencies
Mindlinx Powder Probiotics Used to maintain the integrity and health of the intestinal track. “Lactobacillus acidophilus”
Cholecalciferol Vitamin D3 For the treatment of vitamin D deficiency or insufficiency, familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy
Medications
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LAB VALUES : Blood Gases
22.09.2016 Normal RangepH 7.4 7.35-7.45
pCO2 42 42-48 mmHgpO2 149 35-45 mmHg
HCO3 28 20-27 mmol/LtCO2 28 23 to 29 mEq/L BE 2 -2.0- 2.0 mEq/L
SpO2 99 94% to 99%iCa 1.31 1.10-1.30 mmol/L
HIGH LOW Normal ** No Data Provided
Lab Values: General Chemistry 22.10.2016 Normal Range
Sodium LVL 135 136-145mmol \ L
Potassium LVL 4.2 3.6-5.1mmol\L
Chloride LVL 103 101-111 mmol/L
Calcium 2.42 2.23-2.60 mmol/L
Creatinine 27 44-88micromol/L
Urea level 4.4 2.9–7.1 mmol /LTotal protein 70 61-79
Bili Total 5.3 5.0-21.0 micmol/LBili Direct <1.7 1.7- 8.6 micmol/LAlbumin 37 35-48 IU/LAlk Phos 119 118-360 IU/L
AST 19 15-41 IU/LALT 17 14-54 IU/L
Iron Lvl 10.3 5.0-30.4 micromol/LTransferrin 2.34 1.90- 2.80 g/LGlucose Lvl 5.3 3.9- 6.1 mmol/L
HIGH LOW Normal ** No Data Provided
Lab Values: Complete Blood CountCBC 22.10..16 Normal Range
WBC 8.6 4.5 – 11.0 *10^12/L
RBC 4.63 3.80- 5.10 *10^12/L
Hgb 105 117-155 g/L
Hct 0.33 0.33-0.41 L/L
MCV 71.9 81-100fL
MCH 22.7 25–31 pg
MCHC 315 320-360 g/L
Platelet 221 140-400x 10^9/L
HIGH LOW Normal ** No Data Provided
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Intake and output “last 24 hours”
Total intake including; NG feeding, flushes, medications 1690ml
Total output 912 ml
Balance 778ml
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.10.2016 NORMAL RANGE
Oral Temperature 36.3 36-38.1 degC
Systolic Blood pressure 113 90-140 mmHg
Diastolic Blood Pressure 77 60-90 mmHg
Respiratory On Trichotomy ; room air
Skin Integrity Nil Ulceration ; Nil edema
Activity level Bedridden
GCS (Glasgow Coma Scale) 7/15
Bowel motion Soft ; nil constipation
GI Nil vomiting , nausea episodes ; excessive salivation
Assessment &Vital Sign
HIGH LOW Normal ** No Data Provided
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28ASSESSMENT Interpreting the subjective and objective information's ..
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Anthropometric assessment
• % weight change= (23−26.7)/23×100= -16% weight Significant gain during 1 months. Possible justification due to fat malabsorbtion.
Reference: Sucher, Kathryn P.; Nelms, Marcia; Roth, Sara Long; and Lacey, Karen, "Nutrition Therapy and Pathophysiology" (2011).
Patient BMI classification above 90 precentral:
OVERWEIGHTYet due to patient’s length her
weight considered normal
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Signs and Symptoms Assessment• Salivations on of side effects of the disease
• Clogging tin tube feeding due to camel milk powder.
• Yellowish urine indicates that patient is hydrated well.
• Regarding the GI, without the laxatives and fiber the patient will suffer from constipation as a normal side effect of the disease. the enteral neural plexus may all be affected, leading to gastrointestinal tract manifestations, namely those involving disorders of peristalsis.
Physical Activity Assessment• Patient Bedridden
Parsons T, Weimer L, Engelstad K, et al. Arch Neurol 2010
Dietary Habit Assessment • About Children's OmegaBerry: an emulsified fish oil with tropical
fruit & berry concentrates.
No further information form trials or medical associations regarding the cost-effectiveness of this supplement.
Dietary Habit Assessment • About Mindlinx Powder: High potency live bacteria supplement
with added glutamine particularly useful for children.
No further information form trials or medical associations regarding the cost-effectiveness of this supplement.
A study suggested that glutamine shows negative side effect in mitochondrial disease patients. It can destroy the neurons' mitochondria. When glutamine enters into the mitochondria, it reacts with water and yields excess ammonia which lead to encephalopathy. And other studies shows the opposite .
Halim MA1, Almatarneh MH, Poirier RA.et al. J Phys Chem B. 2014
Dietary Habit Assessment • About Mindlinx multinutrient: Multinutrient powder is a combination of vitamins and
minerals for children, with a high concentration of B vitamins, magnesium and zinc, in a tasty, easy to take, powder form.
This multivitamins dose not contain iron supplementation only folic acid.
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Per 25g -Caloris:118 Kcal-CHO: 19.50g-prt.: 6 gPer 10ml -Caloris:11.8Kcal-CHO: 1.95g-prt.: 0.6 g
Per 100ml -Caloris:46 Kcal-CHO: 11g-prt.: 0.1gPer 10ml -Caloris:4.6 Kcal-CHO: 1.1g-prt.: 0.01g
Per 100ml -Caloris:54 Kcal-CHO: 12.5g-prt.: 0.3gPer 10ml -Caloris:5.4 Kcal-CHO: 1.25g-prt.: 0.03g
Per 100ml -Caloris:57 Kcal-CHO: 12.4g-prt.: 0.5gPer 10ml -Caloris:5.7Kcal-CHO: 1.24 g-prt.: 0.05 g
*Nutrition label for the juices (Hollinger juices) and camel milk. Beetroot juice cannot be assessed because the family prepare it at home.
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Feeding Assessment “Current” • Formula prescription: Enteral feeding via NGT; intermittent with Pediasure Fiber1.0 kcal
and goal rate of 85ml/hr (42.5 ml formula diluted in 42.5 ml water) q3 (6,9,12,15,18,21,24,3). Flushing water 20ml pre/post feeding
- Patient meeting 48.8% of her caloric requirements. Due to additive and weight gain it’s impossible to reduce feeding further and to cut of the additives. Regarding the protein and the fluids, the patient met all her requirements.
- The juices casing abdominal distention for the patient. Once it’s stopped it’s the symptoms is no longer shows
- Camel milk powder causing the tube feeding to clot which may lead to inadequate enteral feeding infusion.
*Taking the average for nutrition content.
Formula BeneProtein Benefiber
ADDITIVES
Flushing Consumed Estimated needs
% of meeting requirementsCamel
Milk powder 10ml
Honey 5ml
Juices 10ml *
Calories ‘Kcal’ 680 75 90 11.8 20 5.2 - 528 kcal 519kcal/day 48.8%
Protein ‘gm’ 10.5 18 0 0.6 - 0.03 - 29g 21-29g/day 100%
Fluid ‘ml’ - 120 240 10 5 10 710 1775ml 1620ml/day 100%
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Laboratory Assessment
On October 6th , 2016
• Low Creatinine level are not common, but it can be seen with conditions that result in decreased muscle mass.
• Low (Hgb, MCV, MCH, MCHC) indicates iron deficiency anemia and/or thalassemia. Other justification for low iron store could be due to Hijama.
• Normal PH, high pO2 and High HCO3) indicates metabolic alkalosis. Respiratory compensation causes an increase in PCO2; therefore the condition is metabolic alkalosis with shifting the body from metabolic acidosis.
• Slightly High iCa level indicates possible excess vitamin D intake
• Low Bili direct level are usually not a concern but may indicate hypoxia.
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NAME Interactions Hyaluronic acid -
Ipratropium bromide Fast/pounding heartbeat, difficult/painful urination.
Scopolamine -The administration with grapefruit juice may delay the absorption and increase the bioavailability of oral scopolamine. The proposed mechanism is delay of gastric emptying. -Blurred vision; chest pain or discomfort; difficulty with urinating; dilation of the pupils; eye pain; muscle weakness; nausea or vomiting.
Levetiracetam -Take without regard to meals. Food does not affect bioavailability.-The serum concentration of Levetiracetam can be increased when it is combined with Scopolamine.
Calcium Carbonate Food increases the absorption of calcium carbonate.
Esomeprazole Take without regard to meals.
3% Sodium Chloride -
Movicol Adult -
Fluticasone High dosages have been associated with precipitation or aggravation of angina, myocardial ischemia, cardiac arrhythmias and hypertension.
Omega-3 -
Multivitamins -
Mindlinx Powder -
Cholecalciferol -
Food- Drug Interactions
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PES Statement
• Overweight (NC-3.3) related to metabolic dysfunction as evidenced by BMI above 90 th percentile.
• Non adherence to nutrition related recommendations (NB-1.6) related to disbelief in science based nutrition information's secondary to desire for a cure for a chronic condition through the use of alternative therapy as evidenced by adding camel milk, juices and herbs to the tube feeing
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39PLAN
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Goals of Nutrition Therapy• Goals of nutrition intervention include the following:
1. Provide adequate enteral nutrition feeding via NGT.
2. Age appropriate weight gain and liner growth.
3. Nutrition reinforcement for parents.
4. Adherence to nutrition recommendation for parents.
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Nutrition Intervention • Formula prescription: Enteral feeding via NGT; intermittent with Pediasure Fiber1.0 kcal
and goal rate of 85ml/hr (42.5 ml formula diluted in 42.5 ml water) q3 (6,9,12,15,18,21,24,3) . Flushing water 20ml pre/post feeding
- Ensure patient's head is elevated 30-45degrees from horizontal whilst enteral feeding plus additional 30 to 60 minutes after to prevent aspiration
- *Taking the average for nutrition content.
Formula BeneProtein Benefiber
ADDITIVES
Flushing Consumed Estimated needs
% of meeting requirementsCamel
Milk powder 10ml
Honey 5ml
Juices 10ml *
Calories ‘Kcal’ 680 75 90 11.8 20 5.2 - 528 kcal 519kcal/day 48.8%
Protein ‘gm’ 10.5 18 0 0.6 - 0.03 - 29g 21-29g/day 100%
Fluid ‘ml’ - 120 240 10 5 10 710 1775ml 1620ml/day 100%
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Follow-up • Growth and weight change trends. ( monthly)
• Family compliance with nutrition recommendations “reinforcement”
• Monitor Labs and body gases (monthly) or as needed.
Recommendations Discussed with the Dr.Javed to consider the following:
• To manage Thalassemia: iron / folate. *
*Keeping in mind if iron overload occurs, avoid using multivitamin and mineral supplements that contain large amounts of iron and vitamin C.
FOLLOW-UP PLAN The main goal for all the follow-ups is Nutrition education reinforcement
Follow-Up1: 27.10.2016• Discussed with family the option to reduce the dose of juices and milk and they agreed on that.
• Patient had a dental appointment and physiotherapy session at TAWAM hospital .
• I asked the nurse regarding the update and no progress regarding the condition.
• Bowel motion: changed 2 dippers for the last 24hrs.
• Total intake: 1725ml / Total output: 1063ml / Balance: +662 ml
Follow-Up2: 30.10.2016• During the weekend the patient went for family visit.
• The parents reduced the amount of additives form 10 to 5 ml as agreed.
• The nurse found redness around the tracheotomy and neck.
• Bowel motion: passed long 2 motion with right after giving laxatives “ per nurse and mother report”
• Total intake: 1730ml / Total output: 1523ml / Balance: 207 ml
Follow-Up3: 31.10.2016• Reinforce the family regarding the amount of additives they add.
• Ask the family to inform the nurse about the mount added so the total intake will be accurate and medical team will be informed about any practices by the family which will ensure a effective medical and nutritional therapy for the patient.
• Reinforce the father about how important to find a gray area with the multidisciplinary team and work together for the sack of his daughter health.
• Bowel motion: changed 2 dippers for the last 24hrs.
DISCHARGE PLAN
AMANA “long-term” Healthcare protocol:
Patient under palliative care; continuous of care will be taking and no discharge plan unless if the patients will go abroad for
treatments per family request.
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47RESEARCH QUESTION ?!
Mitochondrial diseases: An update of dietary management ?
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48A. Karaa et al. Molecular Genetics and Metabolism (2016)
• Objective: to better understand the landscape of dietary supplement use by MD patients. We assessed the types and doses of supplements used by patients with MD and whether any subjective improvements have been noted
• Study Design: online comprehensive questionnaire
• Method: The survey was directed at patients and parents of patients who are or have been on dietary supplements (2-3 weeks) and included 20 questions divided into four parts.
• Part 1 queried the primary mitochondrial disease diagnosis and symptoms that impacted patients the most. • Part 2 explored the nature of the dietary supplements used, their side-effects, their cost and whether their use had
impacted any of the symptoms they described as most bothersome. • Part 3 assessed whether other adjunct therapies were used to treat mitochondrial disease and, if so, whether they
contributed to symptoms improvement. • Part 4 evaluated patient satisfaction with dietary supplements use, cost and financial burden incurred if paying out-of-
pocket.
The dietary supplement online survey was completed by 162 respondents: 59% were patients and 41% caregivers of patients with mitochondrial disease
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The three most represented diseases were: 20% mitochondrial myopathy 10.7% complex I deficiency10.7% chronic progressive ophthalmalgia
More than half of the patients Mitochondrial DNA disease such as MELAS (5.6%), Leigh Syndrome (4.4%) and MERRF (4.4%) were
also well-represented
“The survey did not specifically ask about the genetic mutations for each subject, provided diagnoses are self-reported"
A. Karaa et al. Molecular Genetics and Metabolism (2016)
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Q: How many dietary supplements have you/your child been taking?
75% of patients reported taking four or more supplements at once.11% of patients reported taking only one supplement.
The most commonly used supplements included: 42.5% coenzyme Q10
36% L-carnitine 26.5% riboflavin24% vitamin D 15% vitamin C
In total, 25 different supplements were being used by patients with mitochondrial disease in various combinations that were almost unique to each patient.
68 out of the 162 respondents reported other over-the- counter products that they were regularly using to treat their symptoms
A. Karaa et al. Molecular Genetics and Metabolism (2016)
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72% reported no side-effects. Among the 36 patients who reported having side-effects attributed to the dietary supplements.47% Nausea and upset stomach 36% Unpleasant or increased body odor 8% Vomiting 17% Diarrhea Strategies used to minimize side-effects: 21% Decrease in dose 11.5% Altering timing of supplement intake17% Intake with food 10% Combining the supplements 8% Changing brands
“There would be no definitive method to attribute a side effect to a specific supplement in these cases especially when some patients were not only on
supplements but also on other prescribed medications concomitantly.” A. Karaa et al. Molecular Genetics and Metabolism (2016)
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52A. Karaa et al. Molecular Genetics and Metabolism (2016)
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• Objective: exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners.
• Study Design: workshop sponsored by the National Institutes of Health (NIH), the Wellcome Trust, and the United Mitochondrial Diseases Foundation.
• Method:
The workshop focused on nutritional interventions that have a regulatory definition rather than on general nutrition related topics such as the
macronutrient composition of the diet or mode of delivery, such as whether taken by mouth or via a gastrostomy tube.
K.M. Camp et al. Molecular Genetics and Metabolism (2016)
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A randomized, double-blind, placebo-controlled, crossover study that included 17 patients with a definitive or probable diagnosis of mitochondrial disease
Methods: subjects were administered a combination of 3 compounds (3 g creatine monohydrate plus 300 mg alpha-lipoic acid plus 120 mg CoQ10) twice daily for 2 months following a 5-week washout
period. All patients were then given placebo for 2 months.
Treatment was statistically significantly associated with lower resting lactate concentrations, prevention of loss of strength at the ankle, improved fat-free mass.
Patients with MELAS showed the greatest improvement with the combination therapy, suggesting that one therapeutic strategy may not benefit all mitochondrial diseases.
Reports from clinical trials
M.C. Rodriguez, J.R. MacDonald, D.J. Mahoney etal Muscle Nerve (2007).
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A review of clinical trials for mitochondrial disorders it has been noted that anecdotal reports do not allow evidence-based conclusions for therapy with nutritional interventions. In addition, the controlled clinical trials that have been performed were viewed as weak, with studies on five or fewer patients or inadequate supplement dose.
A uniform multisupplement therapy for mitochondrial therapy is not a reasonable approach for a variety of reasons. Perhaps most importantly, a single approach to treating hundreds of different diseases is not likely to be effective. Moreover, the approach is expensive, and most of the cost is borne by the patients themselves. Regimens including multi- ple medications and dosing patterns are only able to be carried out by highly motivated parents or patients. Finally, aside from “n of 1” cases, opportunities to judge clinical efficacy are limited. These challenges lead to a conundrum for clinicians. Anecdotal reports of efficacy provide hope to patients, but the regimens seldom meet therapeutic goals. Ex- pansive use of vitamins also sometimes is viewed as suspect by physi- cians not routinely involved in treating mitochondrial disease, especially if the patient does not have genetic proof of their illness.
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There is a lack of consistency in what is, and what should be included in combination supplements and there is also a lack of evidence regarding the effectiveness of dietary supplements used in MD.
Dietary Supplements are not regulated as drugs and are not required to conform to the same premarket evaluation process as drugs
There is limited understanding of the bene- fits and risks associated with long-term dietary supplement use.
Issues related to access to dietary supplements include insurance coverage and the high costs to patients and families.
Nutritional Challenges and Opportunities
The issue for conducting researches is recurrent patient due to extreme heterogeneity in these conditions.
K.M. Camp et al. Molecular Genetics and Metabolism (2016)
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Nutritional Challenges and Opportunities
Biomarkers, outcome measures, and endpoints
A key question facing researchers in the field of MD is: What bio- markers for monitoring disease exist and are
feasible and clinically useful ?
Clinical trial designThere’s a need to evaluate any
intervention critically with regard to the inclusion criteria and stratification of
subjects, dose and duration of treatment, and study endpoints.
K.M. Camp et al. Molecular Genetics and Metabolism (2016)
Standards of clinical care for patients with MD
Some clinicians are using the keto- genic diet, yet little is known about how it should be
incorporated for those with refractory epilepsy, and there are questions regarding its safety for patients with mitochondrial disease in general.
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Until establishing a standard of care, nutrition implication will be limited to use dietary
supplements use with caution
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THANK YOU !