SeleniumCarnitine Deficiency and Cardiomyopathy

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Selenium/Carnitine Deficiency and Cardiomyopathy

• Dr. Elena Pope, MSc, FRCPC
• Assistant Professor
• University of Toronto

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Objectives

• Overview of selenium and carnitine deficiency
• Understand epidemiology of CM
• Discuss possible mechanisms of DCM in EB
• Future directions

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Selenium

• Essential trace element
• Potent antioxidant (CVD, cancer)
• Found in kidneys, nuts, liver, fish, brewers
  yeast

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Selenium deficiency

• Animals
• ECG abnormalities
• Myocardial disease mulberry heart
• Humans
• Keshan disease (myocardial necrosis)
• Threshold effect in atherosclerosis
• Skeletal muscle dysfunction with prolonged TPN
• Med Sci Monit 20039(1)RA9-18
• Cell Mol Life Sci 2006 6352-9

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Selenium

• Selenium DRI (RDA)
• 0-6 months 10mcg
• 6-12 months 15mcg
• 1-10 years 20mcg-30mcg
• 11-18 years 40mcg-60mcg
• 18 years 70mcg
• Therapeutic Range 100mcg - 2mg

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Selenium deficiency and DCM

• Possible etiology
• Evidence limited to case reports
• TPN dependent
• Malnourished patients
• HIV
• Mild decrease in EF
• Reversible/improved after replacements

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Carnitine deficiency
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Carnitine

• Trimethylated aminoacid
• Sources
• Diet red meats, dairies
• Endogenous muscle protein catabolism

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Carnitine metabolism
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Carnitine deficiency

• Dietary deficiency ( TPN, soy)
• Malabsorption ( CF)
• Decreased tubular reabsorption
• Carnitine acylcarnitine translocase deficiency

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Carnitine deficiency and CMs

• 51 deficient patients 10 developed CMs
• Am J Dis Child 1987, 141660-5
• 11 CMs- 8 had deficiencies, 6 improved with
  replacements
• J am Coll Cardiol 1988111301-8

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Carnitine deficiency and CMs

• 221 non congenital CMs

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Carnitine deficiency

• No RDI
• If CM use L-carnitine
• Am Heart J 2000 139S63-9
• Replacements
• 25-50 mg/kg/day
• 50-300 mg/kg/day
• (dose for inborn error of metabolism)

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Nutritional Deficiencies and EB

• 14 pts with RDEB
• 36-70 vits and elemental deficiencies
• All asymptomatic
• 61.5 - low selenium
• 61.5- low free carnitine
• No difference between G-tube vs no G-tube
  patients (3 vs 11)

JEADV 2004 18649-53
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Cardiomyopathy

• Pump failure
• 0.6-0.7 /10,000 children
• Forms
• Dilated ( 50 of the cases)
• Restrictive
• Hypertrophic
• Arrhythmogenic Rt ventricular dysfunction

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Cardiomyopathy

• Etiology
• 1/3 ( myocarditis, neuromuscular disease,
  familial, inborn error of metabolism, etc.)
• 2/3 idiopathic
• Prognosis at 2 years
• 14 death
• 13 transplantation
• Finnish study mortality 50
• Poor predictors
• Male gender
• Poor response to Rx
• Low ejection fraction
• Acta Paediatrica 20069545214-16

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Cardiomyopathy

• Presentation
• Insidious (25)
• Acute deterioration (in the context of an
  infection)
• Incidental cardiomegaly
• Acta Paediatrica 20069545214-16

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Cardiomyopathy

• Symptoms
• Cough
• Poor feeding
• Failure to gain weight
• Fatigue
• Shortness of breath
• Decreased exercise tolerance
• Chest pain

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Cardiomyopathy

• Symptoms
• Cough
• Poor feeding
• Failure to gain weight
• Fatigue
• Shortness of breath
• Decreased exercise tolerance
• Chest pain

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Reported cases of DCM and EB
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Cardiomyopathy and EB

• 11 cases reported so far
• Higher incidence than expected
• High mortality within few months from diagnosis
• No uniform mechanism
• Se/carnitine deficiency implicated

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Nutritional deficiency
DCM
?

• Typically seen in DREB
• Worldwide nutrition in EB patients has improved
• Severity of disease does not seem to play a role
• Less cases
• Increased number of cases

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DCM and EB

• Nutritional deficiencies may have an additive
  effect
• Inherent protein abnormality that leads to DCM
  unique to RDEB
• Naxos disease- plakoglobin defect
• EB-MD, plectin deficient mice develop necrotic
  myofibrils

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What to do?

• Screening for DCM
• Yearly cardiac evaluation
• CXR
• ECG
• Echo
• Investigate even subtle changes
• Changes in exercise tolerance
• Nonspecific chest pain
• FTT/excessive weight gain
• Poor feeding

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What to do?

• DCM confirmed
• Baseline
• Hb
• Albumin
• FT Carnitine, selenium, Zn
• Metabolic work-up
• TSH
• Culture and serology for parvo, coxsackie, etc.
• Cardiac muscle biopsy

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Summary

• Se and carnitine deficiency in EB patients
• common
• preventable
• easy to correct
• Yearly cardiac screening in patients with RDEB
• Complete investigation to elucidate etiology of
  DCM in EB