Rett Syndrome in the Pediatric PopulationSara VincenziSodexo Dietetic Intern

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%)

Nighttime feeds?•Continuous @ night to stimulate daytime

appetite.

•8pm-6am @55mL/hour

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.