Failure to Thrive in Toddler

By: Celeste Schwartz, Melissa Rivera, Emily Foley, Yazmin Irazoqui-Ruiz

Introduction

• Failure to thrive

-below average growth pattern

• Underlying Causes: – disease, malnutrition, abuse, & many others

• Used Markers:– Height & Weight

Case Study Overview

• Delayed diagnosis of Celiac Disease in 4 yr. old female.• This presentation will cover

– Patient Medical History– Diagnostic Tests & Results– Treatment– Patient Outcome – Application

****Interactive Presentation: Click on links for further information****

• T-Cell mediated hypersensitivity• Intolerance of wheat products

– Gluten, gliadin and other prolamines• Genetic Component

– 90% of CD patients share MHC Class II HLA-DQ2 haplotype– Remaining 10% share the HLA-DQ8 haplotype

• Occurs in 1/110 Americans

Implications• Hypersensitivity to gluten and gliadin leads to chronic inflammation of the mucosa

in the small intestine→• This leads to the atrophy of the intestinal mucosa→• The villi are in turn damaged which leads to malabsorption of nutrients across the

mucosa.

Atrophied Villi

Atrophied VilliHealthy Villi

Signs and SymptomsResulting from T-Cell hypersensitivity

• Malabsorption• Weightloss• Diarrhea

Clinically Observed

• Bloating & Flatulence• Steatorrhea• Anemia• Weakness• Malnutrition• Vitamin/Mineral Deficiencies• Bone loss• Rashes• Failure to thrive• Attenuated growth• Delayed puberty

Medical History: Birth

• Born at term after an uneventful pregnancy – Weight: 3,230 grams (7.12 lbs)– Length: 52 cm (20.5 in)– APGAR Score: 9, five minutes after birth

• Fed formula from birth

• Decreased growth rate at 6 months

• Gluten introduced to diet at 7 month– No reported gastrointestinal problems

•Parents are unrelated and were healthy during puberty

APGAR Score

• Appearance (skin color)

• Pulse (HR)

• Grimace (reflex irritability)

• Activity (muscle tone)

• Respiration (Breathing rate/effort)

APGAR scores are taken twice: 1 minute after birth and 5 minutes after birth. If there are concerns regarding the infant’s health it is performed again at 10 mins.

Medical History: First EvaluationHISTORY● Reduced growth rate since 6 months (weight & height)● First evaluation at 14 months→ showed slow stature w/adequate weight

TESTS ORDERED○ Free Thyroxine (F4): NORMAL○ Thyroid Stimulating Hormone (TSH): NORMAL○ Anti-transglutaminase antibodies (anti-tTG): NEGATIVE○ Anti IgA: within normal levels for age○ Anemia: Iron deficiency○ Peripheral T&B lymphocyte assessment: NORMAL○ No kidney abnormalities observed w/ultrasound○ No GI distress reported

Case Presentation• 4.1 yr. old female referred to specialists presenting with failure

to thrive and anorexia PHYSICAL EXAM REVEALED• Basal dental hypoplasia• Height of 89.5 cm (−2.79 SDS*)• Weight of 12.5 Kg (BMI −0.76 SDS*)• Delayed bone age of 1.5 years• Growth velocity of 4.83 cm/year (−1.79 SDS*).• Iron deficiency persisted despite iron supplementation*SDS: Standard Deviation Score

What tests would you perform if the parents came seeking a second

opinion?

Tests Performed & Results

SCREENING FOR CD WAS REPEATED:○ IgA-tTG: (128 IU/ml)○ IgG-tTG: (77 IU/ml)

FULL WORK UP FOR CD ORDERED:○ HLA genotyping: HLA DQ2 haplotype → present in 90% of CD Pt’s ○ Duodenal biopsy revealed:

■ severe villous atrophy■ crypt hyperplasia■ intraepithelial lymphocytes

High levels present indicating CD

Intestinal mucosa damage confirmed

CD

Treatment

● Gluten free diet; after 4 months growth velocity increased○ 4.83 cm/year to 6.53

cm/year

Figure 1 Height curve of the subject. The arrow indicates the start of gluten- free diet

Positive CD Diagnosis of Patient ✔

What’s Next? → Family Follow Up

Why?→ Genetic Component of CD

HLA Genotyping of 1st Degree Relatives

PATIENT’S OLDER BROTHER PRESENTS WITH:

○ DQA1*05:01, 05:05 and DQB1*02:01, 03:01 →

○ Negative serology for CD■ Diet still includes gluten■ Repeated serology for CD testing every 3 yrs performed

Indicates HLA DQ2 Haplotype

but w/diff. risk alleles

Discussion

● If there is clinical suspicion of CD the following is indicated:1.) Perform serology → positive IgA-tTG IgG-tTG supports CD diagnosis 2.) Biopsy of SI → histopathological findings confirm CD diagnosis

● Early diagnosis is important to:○ Begin gluten free diet○ Decrease risk of adenocarcinoma & lymphoma →

Occur more frequently in CD Pt’s

Discussion

● CD is not simply a GI disorder → Immune mediated systemic disorder

● Difficult diagnosis of CD because of:○ ↓ prevalence of typical forms (GI symptoms)○ ↑ prevalence of atypical forms (non GI symptoms)

● Seen in this 4.1 yr old female● Only symptom was progressive growth failure

Difficult Diagnosis of CD is Emphasized by this Case

AT 14 MONTHS● Pt presented with no GI symptoms● Pt tested negative for anti-tTG

○ Possibly due to decreased sensitivity of anti-tTG in children <2 yrs

AFTER 3 YR FOLLOW UP● Pt presented w/ high anti-tTG serum levels● Pt was still negative for GI symptoms● HLA Genotyping revealed pt to be heterozygous for HLA DQ2

○ CD is more likely in homozygous HLA DQ2

Suspected CD in Asymptomatic Children

● If HLA DQ2/DQ8 is NEGATIVE: ○ development of CD is unlikely → no need for regular antibody screening

● If HLA DQ2/DQ8 is POSITIVE:○ surveillance of serology should be performed every 3 yrs○ HLA genotyping should also be performed in 1st degree relatives

Application

1. Which of the following diseases may develop if celiac disease is not treated?

A) LymphomaB) OsteoporosisC) AdenocarcinomaD) All of the above

The correct answer is D, all of the above. Undiagnosed and untreated celiac disease can lead to numerous of problems which

can impact various parts of the body.

2. How is celiac disease diagnosed?

A) Anti-tTG-IgA or Anti-tTG-IgG B) A LaparoscopyC) A biopsy of the small intestineD) A and C

The correct answer is D, A and C. An individual suffering with celiac disease has an increased levels of anti-tTG-IgA or anti-tTG-IgG antibodies. These antibodies can be measured with a blood test. If the blood tests suggest celiac disease, the physician would likely order a biopsy of the small

intestine. If the biopsy shows damage to the villi, it will confirm the diagnosis of celiac disease. Without these tests celiac disease would be difficult to diagnose. This is due to the similarity of its

symptoms to those of other diseases.

3. True or False: Family members who are potentially susceptible to celiac disease should get themselves tested.

A) TrueB) False

The correct answer is A, True. Celiac disease is known as a genetic autoimmune disease. This is significant because family members have a higher risk of developing celiac disease more than the general population. Some at risk family members my be asymptomatic, however, those displaying symptoms do not necessary have the disease. Celiac disease can extremely

difficult to diagnose and can show up at any time. It is vital that family members be tested.

4. What common nutrient deficiencies might a patient experience before being diagnosed with celiac disease? A) B12, Copper and Magnesium

B) Iron, Vitamin D and CalciumC) Zinc, Copper and Vitamin DD) None the above

The correct answer is B, Iron, Vitamin D and Calcium. These three nutrient deficiencies are most common. This is due to the intestinal damage caused by

the protein in wheat, barley and rye.

5. True/False: Patients who suffer from celiac disease cannot tolerate gluten.A) TrueB) False

The correct answer is A, True. Individuals susceptible to celiac disease who ingest food containing gliadin experience persistent inflammation of the small intestine due to the autoimmune response induced by the reaction to gliadin.

6. Can the long-term effects of untreated celiac disease be life threatening?A) YesB) No

The correct answer is A, Yes. Serious complications can occur due to malabsorption. This includes osteoporosis, damage to the central and

peripheral nervous systems, and increased risk of lymphoma.

7. What HLA haplotypes are associated with celiac symptoms? A) HLA-DQ2

B) HLA-DQ8C) HLA-DQ5

D) A and B

The correct answer is D, both A and B. HLA-DQ2 and HLA-DQ8 are known to be associated with celiac symptoms. For example, family members lacking these genes do

not have to continue the regular blood tests. Family members who are at risk for developing celiac disease work with their physician to determine how often blood tests

needs to be conducted.

8. A physician reinforces home-care instructions to a patient with celiac disease. Which of the following food items would the physician advise the patient to include in his/her their diet?

A) RiceB) OatmealC) Rye ToastD) Cereal

The correct answer is A, Rice. Dietary restriction is essential to manage the symptoms of celiac disease. All wheat, rye, barley and oat products, which contain gliadins, need to be eliminated from the diet of the patient. These particular instructions need to be taken seriously due to the

longevity of the disease.

9. There is a cure for celiac disease. A) TrueB) False

False: Currently, there is no cure nor effective medication for the treatment of celiac disease. However, dietary management, specifically avoiding foods containing gluten, can reduce its symptoms.

References• Bozzola, M., Bozzola, E., Pagani, S., Mascolo, A., Porto, R., & Meazza, C. (2014). Late

diagnosis of celiac disease in an asymptomatic infant with growth failure. Italian Journal of Pediatrics, 40:4, 1-4. doi:10.1186/1824-7288-40-4

• Braun, C. A. & Anderson, C.M. Pathpphysiology: a clinical approach (2nd Ed). (2011). Philadelphia: Lippincott Williams & Wilkins.

• Venes, D. (2009). Celiac disease, celiac sprue. In Taber’s Cyclopedic Medical Dictionary. (Edition 21, pp 394). Philadelphia: F.A. Davis Company.

• What is the Apgar Score. (2015). KidsHealth. Retrieved from http://kidshealth.org/parent/pregnancy_center/q_a/apgar.html#