Transcript PPS Lecture

Dr. M Shakiba
Subspecialist of pediatric Endocrinology and
metabolism
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Mitochondrial cytopathies are clinically and
biochemically heterogeneous disorders affecting
energy production.
Because of the heterogeneity of disorders , the large
number of biochemical and genetic defects, and wide
spectrum of clinical course, there are limited data
about proven effective therapies.
Treatments for mitochondrial cytopathies are
intended to augment energy production and reduce
the production of free radicals and other toxic
metabolites that further limit the generation of
cellular energy.
Treatment can be aimed at increasing respiratory
chain activity by supplementing relative deficiencies
of cofactors required for proper functioning.
dietary management
supplemental vitamins and cofactors
specific medications aimed at a particular
symptom
Medication
Mechanism of action
Dose
Coenzyme Q10
Bypass complex I and II
2-5 mg/kg/d(5-15)/3 div
doses
Coenzyme Q10
COQ10 deficiency
7.5-30 mg/kg/d
Creatin
Alternative energy source,
neuroprotection
100mg/kg/d
Thiamine
Cofactor for PDH
3-9 mg/kg/d
Riboflavin
Bypass complex I ( via II)
3-5 mg/kg/d(100-400)
Vitamin E
Antioxidant
5-10 mg/kg/d
Vitamin C
Antioxidant
5-10 mg/kg/d
L-carnitine
Treat secondary deficiency
30-50 mg/kg/d
Succinate
Bypass complex I defects
30-70 mg/kg/d
α-Lipoic acid
Antioxidant, Component of
mitochondria
3-5 mg/kg/d
Dichloroacetate
Activate PDH and reduce
lactate
25 mg/kg/d
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The clinical benefits for cofactor and vitamin
therapy can include improved strength and
endurance, although patients report a variety
of benefits.
The use of creatine has been shown to
improve strength in patients with
mitochondrial myopathies, although its longterm use should be be consider with caution
Because of the potential for renal toxicity.
Benefit of Triacetyluridine and magnesium
orotate is contravercial
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The use of antioxidants .(á-lipoic acid, vitamin E,
vitamin C, â-carotene, selenium, vitamin K and Nacetylcysteine) to lessen free radical damage to the
mitochondrial membrane has a scientific rationale,
but again proof of effectiveness does not exist.
The other B vitamins have been used, with reports of
effectiveness in small numbers of patients, likely
those with a rare but specific vitamin-responsive
syndrome.
Treatment with Dichloroacetate associate with some
degree of improvement in several studies. It is
recommended during attacks with high level of
lactate (>10 mmol/l) for short time. Long time usage
associate with peripheral neuropathy
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In critical situations, when lactic acid and
ammonia levels are extremely elevated, the use
of continuous infusion insulin (0.05-0.1 U/kg/h),
using very frequent glucose monitoring, may
help reverse catabolism, decrease circulating
toxic free fatty acids, and lower lactic acid and
ammonia levels.
The use of sodium benzoate, phenylbutyrate,
and sodium phenylacetate can bind conjugate
ammonia in the case of severe hyperammonemia.
Enteral use of lactulose also can help lower
ammonia levels.
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There are no genetic therapies
Exercise:
- with endurance and resistance type exercise
showing evidence of efficacy especially in sporadic
mitochondrial mutation
- They must work within their limit and in play based
exercise
- There are some reports of nausea , vomiting ,
vertigo and and even exercise induced deafness
- avoidance from vigorous exercise during
intercurrent illness and migraine like headache
- Activities such as Tai Chi, Karate, Ballet are helpful
in patients with dyscoordination and ataxia
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Dietary management for mitochondrial disorders
remains largely trial and error.
A low-carbohydrate, high fat diet is helpful for
some patients with complex I deficiency but
others do better on a high-carbohydrate, low-fat
diet.
Patients with PDH deficiency should be treated
with a ketogenic diet.
The use of frequent, small-volume feedings is
generally well tolerated.
For children with primary and secondary
gluconeogenetic defects, avoidance of fasting is
recommended.
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from an anesthetic perspective , the most
important issue is to avoid prolonged periods
of fasting.
avoidance from anesthetic drugs that
predispose to malignant hypertermia
(propofol+local anesthetics(ELMA cream))
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Peripheral neuropathy and other types of
neurogenic pain can be a feature of
mitpochondrial cytopathy
Gabapentin is one of the first line of therapy
Pregabalin had success in patient who can
not tolerate Gabapentin
Another choice is a combination of capsicin
and ELMA(50/50)
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Valprovate sodium should not be used
because it may trigger Rey like syndrome
Topomax is particularly sedating in children
with mitochondrial cytopathy
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In GI problem particularly in MNGIE syndrome
TPN, Simethicone ,Buscopcan
Lactolose and glycerin and high fluid and
fiber diets can be helpful
Mineral oil do not be recommended
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Psychologic support
for patients family
and
for patients