rett syndrome in the pediatric population
TRANSCRIPT
What is Rett Syndrome?•“Rett syndrome is a rare genetic disorder
that affects the way the brain develops. It almost exclusively occurs in girls”
• -the Mayo Clinic
Disease progression:•Normal development from birth-6 months
•Rett syndrome (or RTT) is a progressive disease, broken into 4 stages.▫Results in increased difficulty w/motor
development and related tasks.
Stage 1:•Symptoms are vague
•Typically diagnose at 6 months of age▫When signs of slowed development appear.
•Stage 1 typically lasts from 6 months of age to one year.
Stage 2:•Generally from age 1-4.
•Onset lasts a mere weeks to months.
•Rapid destruction in motor function & loss of muscle coordination.▫Classic hand movements seen in this stage.
Stage 3:•Child plateau’s in terms of disease
progression.▫Symptoms still present, but no further
progression.
•Behavioral symptoms may improve.
•Girls stay in this stage for most of their lives.
Stage 4:•Remain in this stage for decades
•Further decreases in mobility.▫Spinal issues, muscle rigidity & weakness,
increased muscle tone, abnormal body posturing.
•Cognitive decline generally NOT seen.
How does RTT occur?•Mutation in MECP2 –a gene
•Controls MeCP2 protein▫Vital to brain development.▫Biochemical ‘switch’.
•What happens in the MeCP2 mutation?
Girls w/RTT vs. BoysXX chromosome XY chromosome• On in every 10,000-15,000• MECP2 on X chromosome.
▫ Have a ‘back-up” X.• Severity determined by
amount of expression.▫ MECP2 turned off or on
in cells.
• No ‘back-up’ X chromosome.
• Disease will be more destructive and severe as a result.
• See signs immediately after birth.▫ No clinical symptoms.
• Often die shortly after.▫ Only a small amount live
past birth.
Diagnosis:•Three types of criteria needed
▫Main, supportive, & exclusion.
•Diagnosis confirmed by a clinical geneticist, a developmental pediatrician, or a pediatric neurologist.
Focuses of treatment:•Different focuses to lessen the symptoms.
•Antiepileptics
•Physical and speech therapy
•Nutrition support
Nutritional Impact:•Important for normal growth
•Higher calorie requirements
•Nutrition support▫NG or OG tube
GI symptoms:• Difficult to assess and seldom studied/reported on.
• GI dysmotility or other issues related to feeding.▫Chewing/swallowing diffculties, extended feeding
time.
• VBS and upper GI series tests most common procedures for diagnosing.
• ¼ of the cohort had a gastrostomy placed.
GI symptoms:•Similar to those reported by parents’ of
children w/autism spectrum disorder
•Good appetite otherwise▫Better w/modified texture & thickened
liquids
•But increased feeding time
MNT: Justice et al.•Found that neuron function can return if MeCP2
is reintroduced.
•Hemizygous male mice▫Mutation in gene coding for rate-limiting step in
cholesterol synthesis. Had altered brain and systemic cholesterol
metabolism as a result.
•Determined that dz progression and symptoms caused by defect in lipid metabolism.
Justice et al. cont’d.:•Role of cholesterol in brain function
▫Too large to cross blood-brain barrier
•Atypical mitochondrial development ▫Increased prevalence of metabolic
syndrome▫Leading to buildup of ROS
•Tight regulation of cholesterol homeostasis
Justice et al. cont’d.:•84 pediatric girls w/RTT studied
▫Looking at lipid panels▫Had consistently higher lipid levels, all other
labs WNL.
•0-4.9 years: 52% had elevated lipids•5.0-9.9 years: 44% had at least one elevated
lipid marker•10-19 years: 30% had at least one elevated
lipid marker.
MNT: Felice et al.•Possibility of treatment w/omega 3 fatty
acids
•20 children in stage 1 ▫Randomized into one of two groups.
•Looking at primary & secondary outcomes
Felice et al. cont’d.:•Primary outcomes measured via a clinical
severity score▫Parent’s encouraged to videotape children
to examine any clinical changes
•Secondary outcomes measured via blood sampling▫Nonprotein bound iron and various end
products
Felice et al. cont’d.:•Noticeable decrease in CSS criteria seen
in supplement group.▫Observed in videos provided by parents.
•No differences seen on secondary markers in either group.
Presentation of the Pt.:•C.D.
▫11 years old▫Admitted to LVCH March 2nd, 2015
•Admitting dx: ‘seizure disorder’•Adopted
▫Family hx unknown•Birth/developmental hx•3-5 seizures per week
Recent diagnostic tests:•MRI in April 2014
▫Results normal relative to her current state.
•VBS in September 2014▫No further evidence of penetration or
aspiration w/thin or thick liquids.
Meds & labs:•Medications:
▫100 mL D5 ½ NSS, Cerebyx, Vimpat, Carnitor, Ativan, Dilantin, Xantac.
•Labs: WNL aside from the following▫BG: 107, creatinine: 0.25, Ca: 8.9, AST: 15,
Mg: 2.0
Complete lab panel: H/H: 13.9/39.2MCV: 104MCH: 36.8BG: 107BUN: 13Creat: 0.25Na: 142K: 3.9Albumin: 4.0Ca: 8.9PRO total: 6.6AST: 15ALT: 30Alk phos: 277Mg: 2.0
Drawn March 3rd ,2015
Bolded values are below normal limits
Italicized values are above normal limits
Anthropometrics:• Ht: 63 in/136 cm
• Wt: 51.4l b/23.4 kg▫ 2 days later: 27.9 kg
• BMI: 15 kg/m2 k
• DBW: 66 lb/30 kg▫ C.D. @ 93% DBW
• Wt-for-age: 5th percentile• Ht-for-age: 10th percentile• BMI: 10th percentile
▫ Validates dx of FTT
Home diet regimen:•A soft food oral diet
▫Variable intake each day
•4 oz. PediaSure 1.5 Cal TID via PEG after meals▫240 mL▫Another 4 oz. given at night▫4 boluses total-16 oz. per day
PediaSure 1.5 Cal:•Macronutrient breakdown: per 8oz. can
▫CHO: 38g (43%)▫PRO: 14g (16)▫Lipid: 16g (41)
•Designed to meet 100% calcium and vit D DRI’s for children ages 9-13 in 1500 mL of formula.
RDA’s:•C.D. falls in the 11-14 yr age bracket
▫55 kcal/kg or 16 kg/cm of ht.▫Between 1600-2000 kcal/day
Estimated needs: Calories•Estimated using the WHO equation:
▫12.2W(kg) + 746 (11) = 1031 kcals▫Activity/stress factor: 1.3-1.5
▫Total kcal: 1340-1546 kcal/day 58-67 kcal/kg
Estimated needs: Protein & fluid•RDA ages 7-14 is 1.0 g/kg/day.
▫At 23.4 kg, her protein needs are 23 g/day
•Fluid calculated using the Holiday-Seagar method:▫If >/20 kg, 1500mL + 20mL/kg >20kg▫1500mL + 20mL(3.4kg) = 1568mL/day
67 mL/kg
Needs summary:•Kcal: 1340-1546 (58-66 kcal/kg)
•Protein: 23 g/day (1.0 g/kg)
•Fluid: 1570 mL (67 mL/kg)
Nutrition diagnosis statement:•“Inadequate oral intake (NI-2.1) related to
physiologic causes as evidenced by insufficient intake to meet needs, need for EN/TF”.
Interventions:•Pediatric diet: ages 4-14
•Meals and snacks when able & tolerated.
•EN similar to home regimen.
Comparing formulas:PediaSure 1.5 Cal- PediaSure w/fiber 1.0 Cal-
▫ Per 8 oz. can• CHO: 38g (41%)• PRO: 14g (16%)• Fat: 16g (41%)
▫ Per 8 oz. can• CHO: 34g (54%)
▫ 3g dietary fiber▫ 1.5g scFOS
• PRO: 9g (34%)• Fat: 7g (12%)
Summary:Occurring in 1 in 10,000 to 1 in 15,000 girls
Brain cholesterol synthesis & RTT progression
Omega-3 fatty acids in stage I.
Enteral nutrition
No current treatment
ReferencesGrace for Rett. The DSM 5 in plain English [is Rett syndrome autism?. Grace for Rett; February 2014. Available at: http://www.graceforrett.com/rett-syndrome/r168x/the-dsm-5-in-plain-english-is-rett-syndrome-autism/. Accessed on: March 9, 2015.
Rett Syndrome Research Trust. Rett Syndrome. Rett Syndrome Research Trust; 2015. Available at: http://www.rsrt.org/rett-and-mecp2-disorders/rett-syndrome/. Accessed on: March 9, 2015.
Mayo Clinic. Diseases and conditions: Rett syndrome. Mayo Clinic; October 2012. Available at: http://www.mayoclinic.org/diseases-conditions/rett-syndrome/basics/definition/con-20028086. Accessed March 9, 2015.
National Institute of Neurological Disorders and Stroke. Rett syndrome fact sheet. Nat’l Institutes of Health; February 2015. Available at: http://www.ninds.nih.gov/disorders/rett/detail_rett.htm. Accessed on: March 9, 2015.DeWeerdt S. Reclassification of Rett syndrome diagnosis stirs concern. Simons Foundation Autism Research Initiative; July 2011. Available at: http://sfari.org/news-and-opinion/news/2011/reclassification-of-rett-syndrome-diagnosis-stirs-concerns. Accessed on: March 10, 2015.
American Psychiatric Association. DSM. American Psychiatric Association; 2015. Available at: http://www.psychiatry.org/practice/dsm. Accessed on: March 10, 2015.
Motil KJ, Caeg E, Barrish JO, Geerts S, Lane JB, et. al. Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett Syndrome. J Pediatr Gastroenterol Nutr. 2012; 55(3): 292–298.
Justice MJ, Christie Buchovecky et al. A role for metabolism in Rett syndrome pathogenesis. Rare Diseases; 2013. Available at: http://www.tandfonline.com/doi/abs/10.4161/rdis.27265#.VPh_-Wd0zIU. Accessed on: March 29, 2015.
Felice CD, Cinzia Signorini et al. Partial rescue of Rett syndrome by omega-3 polyunsaturated fatty acids (PUFAs) oil. Genes Nutr; 2012. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380188/. Accessed on: March 30, 2015. Abbot Nutrition for Healthcare Professionals. PediaSure 1.5 Cal. Abbott Nutrition; 2015. Available at: http://abbottnutrition.com/brands/products/pediasure-1_5-cal. Accessed on: March 26, 2015. Pediatric Nutrition Quick References. ASPEN Peds Core Curriculum;2010. Pediatric Nutrition Handbook; 2004. Pocket Resources for Nutrition Assessment; 2008. Accessed on: March 26, 2015.
Abbott Nutrition for Healthcare Professionals. PediaSure enteral formula 1.0 Cal w/fiber. Abbott Nutrition; 2015. Available at: http://abbottnutrition.com/brands/products/pediasure-enteral-formula-1_0-cal-with-fiber. Accessed on: March 26, 2015.