Module 02: Inborn Errors of Metabolism Flashcards
This pertains to the inherited diseased caused by interruptions in the various pathways involved in the metabolism of proteins, carbohydrates and or lipids.
Inborn errors of metabolism
What are the modes of transmission for IEM?
Autosomal recessive or X-linked.
Why is early diagnosis and treatment important for IEM?
Early diagnosis and prompt treatment are essential to prevent relentless course of physical and mental deterioration
Do IEMs usually produce symptoms immediately after birth?
No, most show no symptoms in the first 24 hours of life (EPISODIC).
These refer to the sequence of enzyme catalyzed reactions that lead to the conversion of a substance into a final product or excretable form.
Metabolic Pathways
Why are IEM symptoms often confused with other conditions?
They are episodic in nature of metabolic illness. The wide range of clinical symptoms that are associated with more common conditions like infection or sepsis).
Why is diagnosing IEMs challenging?
(A) Low incidence of these disorders.
(B) Lack of experience among pediatric subspecialties.
(C) Need for specialized testing.
What is required for substrate A to become substrate B?
An enzyme or pathway must act on substrate A.
What happens in IEMs regarding metabolic pathways?
There is a problem with the enzyme or hormone needed for metabolism, transformation, or catabolism.
What causes the interruption in the conversion of substrate A to B in IEMs?
A defect somewhere in the enzymatic chain or pathway.
Why is early detection of IEM important?
To identify affected babies before symptoms appear and prevent irreversible outcomes.
What are the goals of early detection in IEM?
(A) Quickly identify affected babies.
(B) Avoid missing cases.
(C) Minimize false-positive results.
(D) Early treatment can begin that prevents the negative and irreversible health outcomes for affected newborns.
What treatments are used for IEM?
These treatments are often inexpensive.
(A) Vitamin supplementation.
(B) Hormone supplementation.
(C) Avoidance of certain foods and chemicals.
(D) Dietary changes.
What technology is used for expanded newborn screening?
Tandem Mass Spectrometry (MS/MS).
How does Tandem Mass Spectrometry (MS/MS) work?
It separates and measures substances by their weight using a few drops of blood (MOLECULAR WEIGHT).
This type of congenital hypothyroidism pertains to the complete or partial absence of functional thyroid tissue or abnormal thyroid gland location.
Primary CH
This type of congenital hypothyroidism pertains to the defect in the brain areas responsible for stimulating thyroid hormone production, not the thyroid gland itself.
Secondary TH or Tertiary CH
What are the thyroid hormones?
(A) Tri-iodothyronine (T3).
(B) Thyroxine (T4).
Why is thyroxine or T4 important for newborns?
(A) Crucial for normal growth and development of the body and brain among newborns
(B) Excreted directly in the bloodstream
(C) Regulates temperature
This is a condition in which an individual does not produce enough thyroid hormone.
Congenital Hypothyroidism
What is the gland involved in congenital hypothyroidism?
Thyroid gland of the endocrine system
What causes Permanent Congenital Hypothyroidism (CH)?
(A) Defective thyroid gland development.
(B) Enzymatic defect in thyroxine synthesis.
(C) Pituitary dysfunction (rare).
What causes Transient Congenital Hypothyroidism (CH)?
Maternal intake of anti-thyroid medication or excess iodine.
What are the different clinical manifestations of congenital hypothyroidism?
(A) Hypotonia – Poor muscle tone.
(B) Prolonged jaundice – Due to immature liver conjugation of bilirubin, ↓ T4.
(C) Inactive defecation.
(D) Umbilical hernia.
(E) Pallor, coldness, and hypothermia – Due to ↓ T4.
(F) Edema and “rough” facial features.
(G) Enlarged tongue.
(H) Rough, dry skin.
(I) Open posterior fontanelles.
(J) Delayed overall development.
What is the appearance of a child with CH before treatment?
Puffed up, dull-looking face, and protruded tongue.
What is the appearance after treatment?
Alert-looking, less swelling, and tongue inside.
What are the late manifestations of CH?
(A) Mental retardation.
(B) Growth retardation.
(C) Delayed skeletal maturation.
(D) Delayed dental development and tooth eruption.
(E) Delayed puberty.
How is CH diagnosed?
- Newborn screening.
- Initial filter-paper blood-spot T4 measurement.
- TSH measurement (if low T4).
Additional tests:
(A) Decreased T4, T3, resin uptake.
(B) Decreased free T4.
(C) Thyroid hormone globulin.
(D) Thyroid scan to check thyroid structure.
What is the treatment for CH?
(A) Thyroid hormone replacement (Sodium L-thyroxine, synthroid, levothroid).
(B) Must be started before the child turns 2 weeks old.
(C) Oral administration of synthetic thyroid hormone indefinitely.
(D) Tablets should be crushed and added to food or a small amount of formula or breast milk.
What should NOT be given when administering thyroid hormone replacement?
Soy-based formulas and iron supplements (avoid during medication administration).
How is Congenital Hypothyroidism (CH) managed?
(A) Monitor T3, T4, and TSH levels to maintain optimum levels (TSH <4 IU/ml).
(B) Ensure early identification of the disorder.
(C) Ensure screening is performed.
(D) Explain to parents that lifelong treatment is required.
(E) Stress the importance of compliance with the drug regimen for normal growth and development
What should be taught to clients or parents with children who have CH in terms of signs and symptoms of drug overdose:
(A) Rapid pulse (heart compensates, BP increases = rapid pulse)
(B) Dyspnea
(C) Irritability (alteration in brain perfusion)
(D) Insomnia (hyper)
(E) Fever (increased thermoregulation)
(F) Sweating
(G) Weight loss (increase metabolic process)
This is a condition where the adrenal glands are enlarged due to abnormal increase in cells.
Congenital Adrenal Hyperplasia (CAH)
This gland is located above the kidneys.
Adrenal Gland
This pertains to the abnormal increase in cells that leads to enlargement.
Hyperplasia
What hormones are secreted by the Adrenal Gland?
(A) Mineralocorticoids (aldosterone, corticosterone).
(B) Glucocorticoids (cortisol, cortisone).
(C) Androgens (estrogen, testosterone).
(D) Catecholamines (epinephrine, norepinephrine).
(E) Peptides (somatostatin, substance P).
What are the parts of the Adrenal Gland and their functions?
(A) Adrenal Medulla
(B) Adrenal Cortex
This part of the adrenal gland has the roles of:
(1) Secretes norepinephrine and epinephrine.
(2) Prepares the body for fight or flight (adrenaline rush).
Adrenal Medulla
This part of the adrenal gland is responsible for the production of glucocorticoids, mineralcorticoids, and androgens.
Adrenal Cotex
Functions of Glucocorticoids.
(1) Stress hormone that responds to stress.
(2) Needed for glucose and protein metabolism.
(3) Protects the body from illness and surgery by increasing gluconeogenesis or decreasing the use of glucose.
(4) Decreases inflammatory response by reducing eosinophils and lymphocytes.
Functions of Mineralcorticoids.
(1) Maintains normal serum sodium levels.
Functions of Androgens.
(1) Responsible for male sexual differentiation.
What are the main functions of the Adrenal Cortex hormones?
(A) Glucocorticoids (Cortisol): Maintenance of normal blood sugar.
(B) Mineralocorticoids (Aldosterone): Maintenance of normal serum sodium.
(C) Androgens (Testosterone): Male sexual differentiation.
What enzyme is needed for the secretion of cortisol, aldosterone, and testosterone to be normal?
21-OH-Enzyme (Hydroxylase)
The 21-OH-Enzyme is crucial for normal adrenal gland function.
What is the result of having a normal amount of cortisol and androgen hormones?
Normal health and sexual development
Adequate levels of these hormones are essential for overall well-being.
What condition is characterized by the absence of 21-OH-Enzyme?
Congenital Adrenal Hyperplasia (CAH)
CAH leads to significant hormonal imbalances.
What are the health effects of decreased cortisol and aldosterone due to the absence of 21-OH-Enzyme?
Multiple health problems
Low levels of these hormones can affect various bodily functions.
What happens to androgen levels in CAH?
Increased androgen levels
Elevated androgen can lead to abnormal physical changes.
What are the consequences of increased androgen levels in CAH?
Genital changes and early puberty
These changes can impact sexual development and reproductive health.
What is the function of 21-hydroxylase (21-OH)?
it tells cortisol and aldosterone in the adrenal gland tp produce if the body needs it. (So congenital hyperplasia also pertains to a decreased production of cortisol)
Congenital Adrenal Hyperplasia is an endocrine problem related to what:
(A) Severe salt loss
(B) Dehydration
(C) Abnormally high levels of male sex hormones in both girls and boys
What inheritance pattern does Congenital Adrenal Hyperplasia (CAH) follow?
Autosomal Recessive Trait
Which enzyme is deficient in CAH (21-hydroxylase deficiency)?
21-hydroxylase (21-OH).
What effect does a deficiency in glucocorticoids (cortisol) have in CAH?
It causes low blood sugar (hypoglycemia).
What is the effect of a deficiency in mineralocorticoids (aldosterone) in CAH?
Low serum sodium and high serum potassium levels.
What effect does excess androgens (testosterone) have in CAH?
Masculinization of females.
What is the salt-losing (salt-wasting) form of CAH characterized by?
A deficiency in cortisol leads to a deficiency in aldosterone, resulting in no salt retention and fluid retention.
What are the immediate clinical manifestations of salt-wasting form of CAH after birth?
(A) Vomiting
(B) Diarrhea
(C) Anorexia
(D) Weight loss
(E) Extreme dehydration
What can happen if the symptoms of salt-wasting CAH remain untreated?
Extreme loss of salt and fluid can lead to shock and death as early as 48-72 hours.
What are the late clinical manifestations of CAH?
(A) Precocious puberty
1. Early sexual maturity and bone maturation
2. Accelerated growth
3. Short adult stature
(B) Pubic hair growth
(C) Oily skin
(D) Body odor
(E) Dark skin color
What is an example of ambiguous genitalia in CAH?
Ambiguous clitoris, where the gender is female but with excessive aldosterone hormones. The orifice may sometimes be fused.
What are the different types of diagnostic evaluation for congenital adrenal hyperplasia?
(A) Congenital Abnormalities
(B) 17-OHP (ketosteroid) levels
(C) 21-complete hydroxylase deficiency
(D) Ultrasonography
What congenital abnormality can make diagnosing CAH difficult at birth?
Difficulty in assigning sex to the newborn due to ambiguous genitalia.
What laboratory test provides a definitive diagnosis of CAH?
Increased serum 17-ketosteroid (17-OHP) levels.
What electrolyte imbalances are seen in complete 21-hydroxylase deficiency?
Loss of sodium and chloride, with elevated potassium levels.
What imaging technique is used to evaluate ambiguous genitalia in CAH?
Ultrasonography
What is the primary medical management for CAH?
Hormonal replacement through hydrocortisone.
What are the roles of hydrocortisone?
(A) It is a synthetic hormone given throughout a newborn’s life to prevent CAH effects.
(2) Recommended at oral dosage that is divided to stimulate the normal diurnal pattern of ACTH secretion.
When should hydrocortisone be taken in individuals with CAH?
Only when CAH symptoms appear to avoid unnecessary hormonal disruption.
What surgical interventions can be performed for CAH-related ambiguous genitalia?
Reconstructive surgery, including:
(A) Reducing the size of the clitoris
(B) Separating the labia
(C) Creating a vaginal orifice
What medications are used to replace deficient cortisol in CAH?
(A) Hydrocortisone
(B) Prednisone
What are the different types of nursing management for congenital adrenal hyperplasia?
(A) Nurses should recognize the genitalia of the newborn.
(B) Explain to the parents about the child’s condition.
(C) Refer to the infant as child or baby rather than he or she.
(D) Refer to the external genitalia as sex organs.
(E) Teach the parents signs of dehydration and its treatment.
(F) Teach parents how to prepare and administer hydrocortisone IM
(E) Refer patients for genetic counseling.
What medication is used to replace deficient aldosterone in CAH?
Fludrocortisone
What is the presence of galactose in the blood called? A metabolic disorder characterized by the body’s inability to use galactose as a source of energy.
Galactosemia
How common is galactosemia?
It is a rare inherited condition with a prevalence of 1 in 20,000 births.
What is galactosemia characterized by?
Abnormal amounts of galactose in the blood due to a defect in carbohydrate metabolism. (The child cannot use galactose as a source of energy).
What enzyme is deficient in children with galactosemia?
Galactose-1-phosphate uridyltransferase (GALT).
What is the function of GALT in normal metabolism?
It converts galactose into glucose.
How is galactosemia inherited?
As an autosomal recessive trait.
Which enzyme converts dietary lactose into galactose?
Intestinal enzyme lactase
Which enzyme converts dietary galactose into galactose 1 phosphate?
Hepatic enzyme galactokinase
What are the different types of diagnostic evaluation for galactosemia?
(A) History taking
(B) Physical Exam
(1) Malnutrition
(2) Dehydration
(3) Decreased muscle mass and body far
(C) Galactosuria (presence of galactose in the urine)
(D) Increased levels of galactose in the blood
(E) Decreased levels of uridine diphosphate (UDP)
Blocked Conversion → Without GALT, Gal-1-P cannot be converted into UDP-galactose.
UDP-Galactose Deficiency → Since UDP-galactose is not formed, UDP-glucose levels also drop, affecting glycogen synthesis.
Cellular Imbalance → The lack of UDP leads to toxic accumulation of galactose and its byproducts (e.g., galactitol), causing damage to the liver, brain, and kidneys.
Does a child with galactosemia appear normal at birth?
YES
What are the early symptoms of galactosemia in newborns?
(A) Poor feeding
(B) Vomiting and occasional diarrhea
(C) Jaundice
(D) Lethargy, weakness, coma
What is the primary dietary management for galactosemia?
Avoid all milk and milk products (including breast milk).
What type of formula is recommended for infants with galactosemia?
Lactose-free or galactose-free formulas, such as soy-based milk formula.
How long must a galactose-restricted diet be followed in galactosemia?
For life to prevent complications.
This condition is known as the glucose-6.-phosphate dehydrogenase deficiency.
G6PD
What is the function of the G6PD enzyme?
It protects red blood cells (RBCs) from oxidative damage.
How is G6PD deficiency inherited?
It is an X-linked recessive disorder.
Which sex is affected by G6PD deficiency?
Males are affected, while females are usually carriers.
How common is G6PD deficiency in Asian babies?
Around 3-3.5% in Malaysia.
What happens to RBCs in G6PD deficiency when exposed to oxidative agents?
Sudden and severe RBC breakdown (hemolysis).
An inherited condition where the body lacks glucose-6-phosphate dehydrogenase (G6PD), leading to RBC damage and hemolytic anemia.
G6PD Deficiency
G6PD deficiency is an inherited condition where the body lacks glucose-6-phosphate dehydrogenase (G6PD), leading to RBC damage and _______________.
HEMOLYTIC ANEMIA
What triggers hemolytic anemia in G6PD deficiency?
Certain medications, foods, and infections.
How many people worldwide are estimated to have G6PD deficiency?
400 million in Africa, Asia, the Mediterranean, and the Middle East.
What is the role of G6PD in preventing hemolysis?
It maintains RBC integrity by reducing oxidative stress.
Are most patients with G6PD deficiency symptomatic?
No, most are asymptomatic unless exposed to oxidizing agents.
What triggers hemolysis in G6PD deficiency?
Exposure to oxidizing agents from certain drugs, foods, infections, and chemicals.
Kids with G6PD deficiency typically do not show any symptoms of the disorder until their red blood cells are exposed to certain triggers, which can be:
(A) Illnesses, bacterial and viral infections
(B) Certain painkillers and fever reducing drugs
(C) Certain antibiotics (especially those with sulf in there name)
(D) Certain antimalarial drugs (those with quine)
(E) SOYA foods
(F) Red wine
(G) Legumes
(H) Vitamin K
(I) Naphthalene
(J) Fava beans
(K) Blueberries
What are the different clinical manifestations of G6PD Deficiency? DA FEAR PJ
(A) Dark urine
(B) Abdominal Pain
(C) Fever
(D) Enlarged spleen and liver
(E) Anemia (Fatigue, Pallor)
(F) Rapid heart rate
(G) Pallor
(H) Jaundice
What are the different types of diagnostic tests?
(A) Check G6PD levels
(B) Bilirubin levels
(C) CBC (Hemoglobin)
(D) Check presence of HgB in urine
(E) Haptoblobin Levels
(F) LDH test
(G) Methemoglobin reduction test
What is the management for G6PD Deficiency?
(A) Limit exposure to triggering factors
(B) Folic Acid
(C) Phototherapy
(D) Blood transfuse
What type of genetic disorder is Phenylketonuria (PKU)?
An autosomal recessive genetic disease.
What enzyme is absent in PKU?
Phenylalanine hydroxylase (PAH).
What is the role of phenylalanine hydroxylase (PAH)?
It metabolizes phenylalanine into tyrosine.
What happens when phenylalanine accumulates in PKU?
It becomes neurotoxic and causes brain damage.
What amino acid becomes deficient in PKU due to the absence of PAH?
TYROSINE
What are the primary neurological symptoms of PKU? (IBH RS)
(A) Intellectual disabilities
(B) Behavioral problems
(C) Hyperactivity
(D) Restlessness or irritability
(E) Seizures
What skin condition is associated with PKU?
Eczema
What distinctive body odor is found in PKU patients?
Musty or mousy body odor.
At what age do the first symptoms of PKU appear?
Around 6 months of age.
How does PKU affect motor development in infants?
(A) Delayed sitting,
(B) Crawling, and
(C) Standing.
How does PKU affect attention and awareness in infants?
Reduced attention to surroundings.
What happens if PKU is left untreated?
Mental retardation and severe developmental delays.
Why does PKU lead to brain damage?
Excess phenylalanine (PHE) accumulates in the blood and tissues, preventing normal brain development.
What is the primary diagnostic test for PKU?
Guthrie bacterial inhibition assay.
What does the Guthrie test detect?
Elevated phenylalanine levels in the blood.
What bacterium is used in the Guthrie test?
Bacillus subtilis.
What is the normal range of phenylalanine levels in newborns?
0.5 - 1 mg/dL.
What is the normal phenylalanine value in the general population?
1.6 mg/dL.
What is the primary dietary intervention for PKU?
Lifelong restriction of protein-rich foods.
When should the PKU diet be started?
As soon as possible, but no later than 7 to 10 days after birth.
What are the clinical management for PKU?
(A) Frequent monitoring of phenylalanine and tyrosine levels.
(B) Teach the family about dietary restrictions
(C) Consume foods low in phenylalanine
(D) Encourage prenatal testing (genetic counseling)
Name some foods low in phenylalanine.
Fruits, juices, cereals, breads, starches, and some vegetables (except legumes).
This condition gets its name from the distinctive sweet odor of affected infants’ urine.
Maple Syrup Urine Diseases (MSUD)
Why is Maple Syrup Urine Disease (MSUD) named as such?
Caused by the byproduct of isoleucine.
What type of disorder is MSUD?
Amino acid disorder
What is the primary defect in MSUD?
The absence of branched-chain ketoacid dehydrogenase (BCKAD) enzyme.
What is the inheritance pattern of MSUD?
Autosomal recessive trait disorder.
What three branched-chain amino acids cannot be broken down in MSUD?
Leucine, Isoleucine, and Valine.
If MSUD is not treated, it is life threatening: (ESSHC)
(A) Episodes where muscles tone alternates between being rigid and floppy
(B) Swelling of the brain
(C) Seizures
(D) High levels of acidic substances in the blood, called metabolic acidosis
(E) Coma, sometimes leading to death
When do the first symptoms of Classic MSUD appear?
3 to 5 days
What are the early signs of Classic MSUD? (Name at least 3)
(A) Poor appetite/feeding
(B) Irritability/high-pitched cry
(C) Incessant crying
(D) Sweet-smelling urine and cerumen
What are the progressive symptoms of Classic MSUD after a few days? (Name at least 3) LSLIC
(A) Limpness with episodes of rigidity
(B) Seizures
(C) Loss of sucking reflex
(D) Increased sleeping time
(E) Coma
What tests are used for diagnosing MSUD? (Name at least 3)
(A) Plasma amino acid test
(B) Urine organic acid test
(C) Genetic testing
There will be signs of ketosis (build-up of ketones, a by-product of burning fat) and excess acid in the blood (acidosis).
What is the primary treatment for MSUD? (Name at least 3)
(A) Medical formula (isoleucine, leucine, valine-free milk)
(B) Low branched-chain amino acid (BCAA) diet
(C) Supplements
(D) Tracking BCAA levels
(E) Liver transplant
What types of foods are recommended for MSUD patients?
Low-protein foods, carefully measured amounts.
What should be considered if a full-term infant presents with lethargy and poor feeding?
Metabolic disorder should be considered, despite sepsis being a common initial thought.
Why is it important to consider metabolic disorders in infants with lethargy and poor feeding?
Infants with IEMs can become debilitated and septic quickly, making it crucial not to exclude other possibilities.
What are the signs and symptoms of metabolic crises?
(A) Extreme sleepiness
(B) Sluggishness
(C) Irritable mood
(D) Vomiting
if metabolic crises is left untreated, what symptoms?
(A) Muscle rigidity
(B) Swelling of the brain
(C) Seizures
(D) High levels of acidic substances in the blood
(E) Coma, sometimes leading to death
What is the goal in preventing IEMS?
100% Newborn Screening Coverage to save more babies from
mental retardation and death.
