6 - Failure to Thrive Flashcards
What is the definition of failure to thrive?
Inadequate weight gain in children due to undernutrition.
What anthropometric measurements are used to assess failure to thrive?
- Weight
- Height
- Head circumference
What is the first indicator of failure to thrive?
Weight change.
What are the two methods for diagnosing failure to thrive?
- Weight below the 5th percentile for sex and corrected age
- Decline in weight measurement by more than two major percentile lines
What is a limitation of using the 5th percentile method for diagnosing failure to thrive?
False identification of constitutionally small infants.
What common symptoms may indicate an organic cause of failure to thrive?
- Diarrhea
- Prolonged vomiting
- Recurrent infection
- Dysmorphic features
- Organomegaly
- Lymphadenopathy
What psychosocial factors are common etiologies of failure to thrive?
- Neglect
- Poverty
- Poor feeding techniques
- Family stressors
- Unusual health and nutritional beliefs
- Poor parenting skills
True or False: Failure to thrive can occur in elderly patients.
True.
What are the common causes of failure to thrive?
- Inadequate caloric intake
- Malabsorption
- Increased energy expenditure
What is the primary biochemical basis for fetal alcohol syndrome?
Effects of alcohol ingestion.
What is the IgA antibody that is specific for celiac disease?
Antiendomysial antibody.
What is dermatitis herpetiformis?
A pruritic papular skin eruption associated with celiac disease.
What does the term ‘forme fruste’ refer to?
An attenuated or unusual presentation of a known illness.
What is the gold standard for the confirmation of celiac disease?
Small bowel biopsy.
What are the two peak ages of onset for celiac disease?
- Early childhood when gluten is introduced
- Fourth and fifth decades
What role do HLA antigens DQ2 and DQ8 play in celiac disease?
They correlate with the presence of disease and help to exclude celiac disease.
What is the clinical impression for a patient with failure to thrive and gastrointestinal symptoms?
Highly suggestive of malabsorption/maldigestion.
What laboratory tests are needed to support a diagnosis of celiac disease?
- Tissue transglutaminase (tTG) antibody
- Antiendomysial antibody
- Normal IgA level
What does a small bowel biopsy in celiac disease typically show?
- Flattened villi
- Deepened crypts
- Increased lymphocytic infiltration
Fill in the blank: The most common malabsorptive entity at this age is _______.
celiac disease.
What is the significance of the index case in a family with celiac disease?
Essential to document the disorder before starting a gluten-free diet.
What can a positive result for tissue transglutaminase (tTG) antibody indicate?
Potential diagnosis of celiac disease.
What is the definition of protein-energy malnutrition?
A condition resulting from inadequate caloric intake leading to weight loss and nutritional deficiencies.
What are the two forms of acute severe malnutrition?
- Marasmus
- Kwashiorkor
What is the role of fecal studies in diagnosing celiac disease?
To check for pathogens, including parasites like Giardia.
What condition is associated with elevated orotic acid?
Defects of the urea cycle or pyrimidine biosynthesis.
What is the primary concern when diagnosing celiac disease in a patient with IgA deficiency?
False negative results in serology testing.
What is the primary utility of testing for HLA-DQ2 or HLA-DQ8 antigens in celiac disease?
To exclude celiac disease from the differential conclusively in patients with suggestive symptoms and negative tTG and antiendomysial antibodies.
It is not intended as a screening test.
What is the molecular basis of celiac disease?
Celiac disease is an autoimmune disorder of chronic small intestinal immune-mediated enteropathy triggered by gluten in genetically predisposed individuals.
It can have extraintestinal manifestations such as iron deficiency anemia, dermatitis herpetiformis, and various neurological symptoms.
What are some extraintestinal manifestations of celiac disease?
- Short stature
- Delayed puberty
- Dental enamel hypoplasia
- Osteopenia/osteoporosis
- Iron deficiency anemia
- Recurrent stomatitis
- Liver and biliary disease
- Dermatitis herpetiformis
- Arthralgia
- Arthritis
- Headaches
- Ataxia
- Peripheral neuropathy
- Epilepsy
- Behavioral changes
- Psychiatric disorders
- Alopecia
These manifestations can be mistaken for other conditions.
What was the Oslo definition of celiac disease in 2013?
A set of recommendations about the terminology to be used in celiac disease to improve communication and minimize misunderstandings.
Terms to avoid include celiac sprue, nontropical sprue, and gluten intolerance.
What is the prevalence of celiac disease among non-Hispanic Whites in the United States?
~1% of the population.
It is more prevalent in women than in men.
How does gluten lead to a T-cell–mediated autoimmune response in celiac disease?
Gliadin binds to enterocytes, leading to a cascade of reactions that results in damage to enterocytes, loss of tight junctions, and malabsorption of nutrients.
This process is facilitated by the release of IL-15 and the activity of tissue transglutaminase.
What is the role of tissue transglutaminase (tTG) in celiac disease?
tTG deaminates glutamine residues of gliadin to enhance its interaction with HLA-DQ2 or HLA-DQ8 on antigen-presenting cells.
This interaction leads to T-cell activation and further tissue damage.
What are the classic findings upon small bowel biopsy in celiac disease?
- Villous atrophy
- Deepening crypts
- Diffuse inflammatory infiltrates
These findings are not pathognomonic and must be supported by positive tTG antibody results.
What is the primary treatment for celiac disease?
Cessation of gluten in the diet.
Patients are also evaluated for nutritional deficiencies.
What are the clinical manifestations of galactosemia?
- Failure to thrive
- Early onset jaundice
- Leukopenia
- E. coli infection
- Cataracts
- Positive nonglucose reducing substance in urine
These manifestations prompt early intervention.
What is galactitol?
The untoward by-product in galactosemia.
It results from the accumulation of galactose due to enzyme deficiencies.
What is the primary source of galactose in the human body?
Lactose, a disaccharide composed of glucose and galactose.
Lactose is broken down by β-galactosidase (lactase) in the brush border of enterocytes.
What enzyme is responsible for converting galactose to galactose-1-phosphate?
Galactokinase.
This process is ATP-driven and ensures that galactose is trapped in the cell.
What biochemical derangement occurs in galactosemia?
An error in the metabolism of dietary galactose, leading to accumulation of toxic metabolites.
This results in various clinical symptoms including cataracts and liver dysfunction.
What is the role of galactose in metabolism?
Galactose can be metabolized for fuel or used for the synthesis of glycolipids, proteoglycans, and glycoproteins.
What enzyme mediates the conversion of galactose to galactose-1-phosphate?
Galactokinase.
What is the significance of galactose-1-phosphate in the cell?
It traps galactose in the cell, similar to glucose and fructose.
What enzyme converts galactose-1-phosphate to glucose-1-phosphate?
Galactose-1-P uridylyltransferase (GALT).
What happens to UDP-galactose in the metabolism of galactose?
It is converted to UDP-glucose by UDP-galactose-4-epimerase.
What is the next step after glucose-1-phosphate is formed?
It is isomerized to glucose-6-phosphate by phosphoglucomutase.
What enzyme removes the phosphate from glucose-6-phosphate in the liver?
Glucose 6-phosphatase.
What is galactitol and how is it formed?
Galactitol is a sugar alcohol formed from galactose by aldose reductase using NADPH.
True or False: Galactitol can be metabolized further after its formation.
False.
What condition can arise from increased concentrations of galactitol?
Increased osmotic pressure leading to tissue damage and cataracts.
What is classic galactosemia?
An inborn error of metabolism due to a deficiency in GALT.
What are the clinical symptoms of classic galactosemia?
Lethargy, vomiting, diarrhea, jaundice, and hepatomegaly.
What complication arises from a defect in granulocyte chemotaxis in classic galactosemia?
High risk of E. coli sepsis.
What dietary change is recommended for infants diagnosed with classic galactosemia?
Elimination of lactose from the diet.
What is orotic acid?
An intermediate in pyrimidine biosynthesis increased in certain metabolic disorders.
What are the symptoms of orotic aciduria?
Failure to thrive, global functional delay, megaloblastic anemia unresponsive to vitamin supplementation, and crystalluria.
What is the most common cause of megaloblastic anemia?
Deficiency in vitamin B12 and/or folic acid.
What is uridine monophosphate synthase (UMPS) deficiency?
An inborn error of metabolism in the pyrimidine synthesis pathway leading to orotic aciduria.
What is the role of the enzyme carbamoyl phosphate synthetase II in pyrimidine synthesis?
It synthesizes carbamoyl phosphate from glutamine and bicarbonate.
What is the effect of pyrimidine replacement therapy with uridine?
It helps with anemia and reduces urinary excretion of orotic acid.
What is the inheritance pattern of ornithine transcarbamylase (OTC) deficiency?
X-linked recessive.
What is the most common cause for renal calculi?
Calcium oxalate crystals.
What can lead to the formation of crystals in the urine?
Supersaturation of ions in the local environment.
What is the typical presentation of a neonate with classic galactosemia?
Symptoms develop when exposed to breast milk or lactose-based formula.
What is the biochemical basis of orotic aciduria?
Deficiency of uridine monophosphate synthase leading to accumulation of orotate.
What can cause crystalluria apart from orotic aciduria?
Gout, pseudogout, and calcium oxalate deposition.
What does treatment reduce regarding orotic acid?
Urinary excretion of orotic acid
What condition can result from ornithine transcarbamylase (OTC) deficiency?
Orotic aciduria
How is the OTC gene inherited?
In an X-linked recessive manner
Why is orotic aciduria due to OTC deficiency more common in males?
Because the OTC gene is on the X chromosome
What happens to end products of pyrimidine degradation?
They are converted into intermediates of the citric acid cycle
What can genetic mutations in dihydropyrimidine dehydrogenase (DPD) enzyme lead to?
Life-threatening toxicity from 5-fluorouracil (5-FU)
What should patients with allelic variants of the DPD gene undergo before treatment with 5-FU?
Genotyping
What is the committed step in de novo pyrimidine synthesis?
Catalyzed by carbamoyl phosphate synthetase II
What feedback mechanism regulates carbamoyl phosphate synthetase II?
Feedback regulated by UTP
What dietary addition inhibits carbamoyl phosphate synthetase II?
Uridine
What are symptoms of hereditary orotic aciduria?
Failure to thrive
Developmental delay
Megaloblastic anemia
Unresponsiveness to folate and vitamin B12 supplementation
What causes hereditary orotic aciduria?
UMPS deficiency in the pyrimidine synthesis pathway
What might orotic aciduria also arise from?
Defects in the urea cycle
What percentage of the overall population has dihydropyrimidine dehydrogenase deficiency?
~5%
What does dihydropyrimidine dehydrogenase deficiency lead to?
Increased half-life of 5-FU and excess drug accumulation
What is kwashiorkor?
Protein-energy malnutrition with edema
Who first described kwashiorkor?
Cecily Williams in 1936
What is marasmus?
Protein-energy malnutrition with wasting
How is protein-energy malnutrition defined?
Metabolic imbalance due to nutritional deficiency
What are the two major classifications of protein-energy malnutrition?
Kwashiorkor
Marasmus
What notable symptoms does kwashiorkor present?
Edema
Hypoalbuminemia
What does severe acute malnutrition describe?
Children with severe wasting and kwashiorkor
What is the estimated number of children with marasmus worldwide?
Approximately 52 million
What percentage of severe malnutrition cases are believed to be kwashiorkor?
50%-70%
What differentiates the metabolic adaptation in kwashiorkor from marasmus?
Disruption due to mitochondrial and peroxisomal damage
What causes the edema seen in kwashiorkor?
Hypoalbuminemia and leakage of fluid from capillaries
What is the main energy source for the brain during prolonged starvation?
Ketone bodies
What happens to glucose levels used by the brain during starvation?
Falls from 90 to 30 mg/dL
What are the metabolic disturbances in marasmus?
Severe loss of muscle and adipose tissue with complete cessation of growth
What is the effect of inadequate intake on children’s growth?
Slowing or stoppage of growth
What type of diet caused kwashiorkor in the case study?
A strict vegan diet
What is the clinical impression of the child with kwashiorkor?
Hospitalized for further analysis and treatment
What test is ordered to evaluate for celiac disease?
tTG antibody test
What is the likely diagnosis suggested by the negative tTG antibody level?
Severe malnutrition, particularly kwashiorkor
What is the difference in metabolic disturbances between marasmus and kwashiorkor?
Marasmus leads to severe wasting while kwashiorkor involves mitochondrial damage and edema
What is the treatment for the child’s kwashiorkor?
Infusion with milk-based feed and nutritional supplements
What are the behavioral problems exhibited by the 5-year-old girl?
Disruptive in class and exhibiting aggressive behavior
The aggressive behavior has been worsening over the past 2 years since kindergarten.
What was the APGAR score recorded for the child?
7
The APGAR score is a quick assessment of the newborn’s health.
What percentiles for height and weight is the child in?
7th percentile for height and 4th percentile for weight
This indicates that she is small for her family.
What significant prenatal factor is noted in the child’s history?
The child’s mother drank alcohol during pregnancy
This is a critical risk factor for developmental issues.
What were the results of the recent testing by the school psychologist?
Delay in speech, reasoning, and memory; placed at a 3-year-old level of intellectual development
This indicates significant developmental delays.
What craniofacial abnormalities were noted during the physical examination?
Small cranium, absence of the philtrum, nasal flattening
These features are indicative of fetal alcohol syndrome.
What was the tentative diagnosis made for the child?
Fetal alcohol syndrome (FAS)
This diagnosis was based on the data at hand.
What is DiGeorge syndrome?
A syndrome caused by multiple gene deletions on chromosome 22, characterized by palatal abnormalities and cognitive defects
It is an autosomal dominant condition, often arising from spontaneous mutation.
What are fetal alcohol spectrum disorders (FASD)?
A spectrum of conditions associated with prenatal exposure to alcohol, including learning and behavioral problems as well as physical problems
Fetal alcohol syndrome (FAS) is at the severe end of this spectrum.
What are neural crest cells?
Multipotent cells that give rise to various cell types in the nervous system and epidermis
These include neurons, glial cells, and cells of the craniofacial complex.
What is neuroapoptosis?
Programmed cell death of brain cells
This process can be influenced by teratogens such as alcohol.
What is the significance of the mother’s alcohol consumption during pregnancy?
It has toxic effects on the unborn fetus, leading to developmental delays and neurological dysfunction
Fetal alcohol syndrome is the most frequent cause of such issues in children.
What is the incidence of fetal alcohol syndrome (FAS) in the United States?
Approaches 1%
This statistic highlights the prevalence of FAS.
What structural abnormalities are commonly associated with FAS?
Microcephaly, hydrocephalus, corpus callosum defects, dysmorphic facial features
These abnormalities can lead to significant cognitive and behavioral challenges.
What is the molecular basis of fetal alcohol syndrome?
Develops from maternal alcohol consumption during fetal development, leading to structural and neurodevelopmental abnormalities
The severity depends on timing, dose, and frequency of exposure.
How is alcohol absorbed in the body?
Alcohol is absorbed mainly in the small intestine through passive diffusion
Food consumption can slow down this absorption.
What is the effect of alcohol on maternal nutrition?
Alcohol can lead to micronutrient deficiencies and restrict nutrition flow to the fetus
This can adversely affect fetal development.
What role does genetics play in FASD?
Genetic polymorphisms in alcohol metabolizing enzymes can affect the severity of alcohol teratogenicity
Variations in these enzymes can influence maternal alcohol consumption.
What is the primary reason for the significant intellectual disability in FAS?
Structural abnormalities in brain development
These abnormalities lead to cognitive delays that often go unrecognized until preschool age.
What is the overall outlook for a child diagnosed with FAS?
The ability to function normally remains bleak
Supportive care is the only option available.
What are the symptoms of the 1-month-old child described?
Megaloblastic anemia, poor growth, feeding difficulties, pale appearance
The child also shows no other abnormalities on physical examination.
What is the most likely diagnosis for the child with megaloblastic anemia refractory to cobalamin and folate?
Deficiency in Uridine monophosphate synthase (UMPS)
This condition is associated with orotic aciduria and specific symptoms.
Which nutrient is most likely to worsen symptoms in a patient with positive tissue transglutaminase antibodies?
Rye
Rye contains gluten, which aggravates celiac disease.
What metabolites are associated with cataract development in the newborn described?
Galactitol
Galactitol is formed from increased galactose levels in GALT deficiency.
What is the most appropriate intervention for the 10-month-old infant with anemia and crystalline sediment in urine?
Uridine
Uridine can bypass the blockage in pyrimidine synthesis due to UMPS deficiency.
What is the likely cause of facial dysmorphic features in the hyperactive 1-year-old child?
Impaired neural crest movement
This is associated with fetal alcohol syndrome.
What is the most appropriate diagnostic test for screening siblings of a child diagnosed with celiac disease?
Antitissue transglutaminase antibodies
This test is specific for celiac disease screening.
What condition is indicated by weight loss, abdominal edema, and irritability in a 1-year-old after being placed on a BRAT diet?
Kwashiorkor
This condition arises from protein-energy malnutrition.
What is the characteristic finding in a child with GALT deficiency?
Cataracts and jaundice
These symptoms result from increased galactose levels.
What laboratory finding is expected in a child with ornithine transcarbamylase deficiency?
Elevated ammonia levels
This condition leads to urea cycle disorders.
What is the role of glutathione in the context of kwashiorkor?
Reduces oxidative stress
In kwashiorkor, glutathione levels are believed to be lower.
What is the expected outcome of high NADH levels in a child with fetal alcohol syndrome?
Inhibition of pyruvate dehydrogenase
This can lead to energy deficiencies.
Fill in the blank: The enzyme deficient in classic galactosemia is _______.
Galactose-1-phosphate uridylyltransferase (GALT)
This deficiency leads to severe symptoms in affected infants.
True or False: Lactase deficiency is the cause of cataracts in infants.
False
Lactase deficiency leads to lactose intolerance, not cataracts.
What are dysmorphisms believed to occur due to?
Impaired neural crest movement and increased neuroapoptosis
Dysmorphisms are structural abnormalities in the body that can arise from various developmental issues.
What inhibits pyruvate dehydrogenase in the context of FAS?
Increased NADH accumulation
Pyruvate dehydrogenase is crucial for converting pyruvate into acetyl-CoA, and its inhibition can lead to energy deficiencies.
What is the best screening test for celiac disease?
Antitissue transglutaminase antibodies (tTG)
This test has high specificity and sensitivity, especially in patients with a family history of the condition.
What happens to tTG antibodies when a patient strays from a gluten-restricted diet?
They become positive and correlate with inflammatory reaction in the gut
Monitoring tTG levels can help assess adherence to the diet in celiac disease patients.
What are the less sensitive and specific tests compared to tTG for celiac disease?
Antigliadin antibodies and antiendomysial antibodies
These tests can provide information but are not as reliable as the tTG test.
When is a small intestinal biopsy usually necessary in celiac disease diagnosis?
When first establishing the diagnosis in the index case
A biopsy can confirm celiac disease but may not be needed for follow-up if tTG is positive.
What mucosal changes are not pathognomonic for celiac disease?
Flattened villi and deepened crypts along with inflammatory change
These changes can occur in various malabsorption disorders, not just celiac disease.
What are classic facial dysmorphic features of fetal alcohol syndrome (FASD)?
Thin upper lip, smooth philtrum, and small eye openings
These features help in the identification of FASD in affected individuals.
What is a common misconception regarding DiGeorge syndrome and fetal alcohol syndrome?
They share common dysmorphic facial features
However, the context of the mother’s social history is crucial to differentiate between the two syndromes.
Which deficiency can lead to failure to thrive but presents with jaundice, hepatomegaly, and cataracts?
Galactose-1-phosphate uridylyltransferase deficiency
This condition is distinct from FASD and has specific clinical presentations.
Why is kwashiorkor unlikely in a breastfed child who is also fed formula?
The child’s failure to grow is not due to protein deficiency
Kwashiorkor is typically associated with inadequate protein intake, which is less likely in this scenario.
