Week 10

Question 1

Ashkenazi Jewish decent are higher risk for

Answer 1

Gaucher, Tay-Sachs, Canavan

Question 2

Mediterraneans are higher risk for

Answer 2

Beta-Thalassemia, Sickle-Cell

Question 3

French-Canadians are higher risk for

Answer 3

Tay-Sachs, Branched-Chain Ketoaciduria

Question 4

Northern Europeans are at higher risk for

Answer 4

CF and PKU

Question 5

West Africans at greater risk for

Answer 5

Sickle cell and sickle cell-hemoglobin C

Question 6

Glactosemia inheritance

Answer 6

Autosomal recessive

Question 7

Glactosemia Definition/Patho

Answer 7

Deficiency of galactose-1-phosphate urindyltransferase enzyme that converts galactose to glucose in the digestion of lactose.

Question 8

Glactosemia Signs and Symptoms

Answer 8

Intrauterine growth restriction (IUGR), vomiting and diarrhea during lactose feeds, hypoglycemia, Gram-negative sepsis (E. coli), hepatic damage with secondary hyperbilirubinemia, hepatomegaly, cirrhosis, urine positive for reducing substance, cataract development ~3 months of age.

Question 9

Glactosemia Basic Treatment

Answer 9

Lifelong dietary restriction of lactose. Aggressive surveillance and treatment of sepsis.

Question 10

Maple Syrup Urine Disease (MSUD) Inheritance

Answer 10

Rare autosomal recessive trait

Question 11

Maple Syrup Urine Disease (MSUD) Definition/Patho

Answer 11

Elevated serum levels of leucine, isoleucine, valine, and their corresponding ketoacids.

Question 12

Maple Syrup Urine Disease (MSUD) S/S

Answer 12

Symptoms are usually evident within the first 48-72 hours of life, and include lethargy, poor feeding, vomiting, weight loss, abnormal tone, seizures, and loss of reflexes. Urine characteristically has maple syrup odor. Milder variants are asymptomatic during the newborn period.

Question 13

Maple Syrup Urine Disease (MSUD) Treatment

Answer 13

Treatment includes peritoneal/hemodialysis and discontinuation of protein intake. Long-term treatment includes dietary restrictions, including limitation of branched-chain amino acids (especially leucine); they should be titrated using special formulas along with fruits, vegetables, and low-protein foods. Thiamine may stimulate dehydrogenase activity.

Question 14

PKU Inheritance

Answer 14

Autosomal recessive

Question 15

PKU Definition/Patho

Answer 15

Deficiency or absence of phenylalanine hydroxylase, which is a enzyme that is require to convert phenylalanine to tyrosine. Blocking this conversion result in build up of phenylalanine in body fluids and lead to CNS damage

Question 16

PKU S/S

Answer 16

Apparent at 3 months- vomiting, feeding difficulties, irritability, infantile eczema, hypopigmentation of skin and hair, musty odor urine.

Question 17

PKU Treatment

Answer 17

Phenylalanine-restricted diet, <15-20mg/dL

Question 18

Sickle Cell (hemoglobinopathies) Inheritance

Answer 18

Autosomal recessive sickle gene carried by about 10% of African-Americans in the U.S.

Question 19

Sickle Cell S/S

Answer 19

Onset of symptoms usually occurs around 4 months of age; symptoms may include: hand-foot syndrome (low-grade fever, painful swelling of hands/feet due to meta-carpal/tarsal bone infarction), splenic sequestration crisis (vascular collapse from splenic pooling of blood, anemia, splenomegaly, hypotension), and frequent life-threatening infection.

Question 20

Sickle Cell Treatment

Answer 20

Treatment is primarily symptomatic, and includes restoration of intravascular volume, RBC transfusions, splenectomy, prophylactic antibiotics, and pneumococcal vaccination.

Question 21

Congenital Adrenal Hyperplasia Inheritance

Answer 21

Autosomal recessive

Question 22

Congenital Adrenal Hyperplasia Definition

Answer 22

Disorder of the adrenal glands in which there is a block in the production and manufacture of the stress hormone cortisol. The classic and nonclassic forms of the disease are caused by deficiencies in the adrenal enzymes used to synthesize glucocorticosteroids.

Question 23

Congenital Adrenal Hyperplasia S/S

Answer 23

Simple virilizing form- ambiguous genitalia. Salt-wasting form- adrenal crisis between 1 to 4 weeks of age. Presents with poor appetite, vomiting, failure to grow, and potentially fatal electrolyte and water imbalance.

Question 24

Congenital Adrenal Hyperplasia Treatment

Answer 24

Glucocorticoid replacement therapy for all patients with CAH (regardless of form). Patient’s with salt-wasting form form of deficiency must also receive mineralcorticoid therapy to normalize the abnormalities in sodium balance associated with aldosterone deficiency. Surgical procedures are used to correct the genital abnormalities of girls with virilizing form of CAH.

Question 25

Medium Chain Acyl-Coenzyme A dehydrogenase Deficiency (MCAD) Inheritance

Answer 25

Autosomal Recessive

Question 26

MCAD Definition

Answer 26

Defects in fatty acid transport or the mitochondrial beta-oxidation pathway leading to inability to metabolize fatty acid. May be asymptomatic or have premature death.

Question 27

MCAD S/S

Answer 27

Fasting/ stress/ illness lead to hypoketotic hypoglycemia, hypotonia, muscle weakness, lethargy, and vomiting progressing to seizures, coma, encephalopathy and death.

Question 28

MCAD Treatment

Answer 28

Avoid fasting. Infant should avoid fasting longer than 3hrs for first 3 months. IV glucose infusion during illness and fever. Monitor carnitine level and supplement with PO carnitine 50-100mg/kg/day if level is low.

Question 29

When do they normally do newborn screening test?

Answer 29

Not before 24 hours. Not after 72 hours. Obtain as late as possible before discharge, but no later than 72 hours. If done before 24 hours, rescreen within 14 days or 1-2 week (avoids false negatives).

Question 30

How is newborn screening test done?

Answer 30

Done by heel stick blood sample.

Question 31

All states screen for

Answer 31

PKU, galactosemia, and congenital hypothyroidism.

Question 32

Start treatment _________for galactosemia or maple syrup urine while waiting for confirmation since they can be life threatening.

Answer 32

Immediately

Question 33

Galactosemia

Answer 33

A lot of times babies will have diarrhea, vomiting, can cause IUGR. May feel enlarged liver (hepatomegaly) upon palpation. May see cataracts in eyes. Muscle tone is hypoactive. Can you breastfeed? Contraindicated. Usually on soy-based formula. Fatal if not treated.

Question 34

Maple Syrup Urine Disorder

Answer 34

Sweet smelling urine d/t ketones in urine being broken down (ketoacidosis). Must diagnose early. Can die in the first few weeks. Chronic treatment is dietary, with limitation of branched-chain amino acids, especially leucine, titrated through use of special formula along with fruits, vegetables, low-protein foods. Avoid protein and amino acids. Fruits and vegetables, low protein diet.

Question 35

PKU

Answer 35

Musty smell to urine caused by PKU. Skin change of eczema. Treatment: Well-controlled phenylalanine-restricted diet for classical PKU (specialized formula, ongoing adjustments).

Question 36

Differentiation between Maple Syrup and PKU is

Answer 36

the smell to urine. Maple syrup is sweet and PKU is musty.

Question 37

Congenital Adrenal Hyperplasia

Answer 37

All patients with CAH, regardless of form, are treated with glucocorticoid replacement therapy. Given to replace cortisol. Caused by deficiency in adrenal enzymes. Glucocortcoids help with that. Females can have virilization (ambiguous genitalia) d/t extra adrenal production. Salt-wasting form—adrenal crisis between 1 to 4 weeks of age, presenting with poor appetite, vomiting, failure to grow, and potentially fatal electrolyte and water imbalance.

Question 38

MCAD

Answer 38

Don’t have enzyme needed to convert fat to energy. No skipping meals. Follow strict feeding schedule. Avoid fasting. With illness or periods of stress, may need IV glucose administration (10% dextrose). If untreated, can lead to hypoglycemia, muscle weakness, seizures, vomiting, coma, death.

Question 39

Sickle Cell

Answer 39

Most concerning is a crisis. Splenic crisis, cerebrovascular accidents, frequent life-threatening infections. As soon as diagnosis confirmed: treated with prophylaxis of penicillin to make sure they don’t get infection/pneumonia.

Question 40

Congenital Hypothyroidism

Answer 40

Infants with thyroid agenesis will have the classical findings of atypical facies, hypertelorism, exophthalmos, short nose, enlarged protruding tongue, large fontanelles, and umbilical hernias. Untreated hypothyroidism results in mental retardation, delayed development, constipation, feeding difficulties, poor growth, hypothermia, and hypoactivity. Treated with lifelong replacement of synthetic T4 (Levothyroxine). Labs show low T4 and high TSH. Trisomy 21 (Down Syndrome) has higher incidence of hypothyroidism.

Question 41

Down Syndrome/Trisomy 21 S/S

Answer 41

Brachycephaly, hypotonia, hyperlaxity, oblique palpebral fissures, protruding tongue, flat nasal bridge. Small ears, Brushfield spots, short/wide hands, palmar simian creases, epicanthal folds, wide gap between 1st and 2nd toes, growth retardation, mental retardation. At higher risk for leukemia, Alzheimer disease, hypothyroidism. Must be screened more aggressively for cardiac, vision, hearing. Screen for mitral valve prolapse at adolescence.

Question 42

Down Syndrome/Trisomy 21 Screenings

Answer 42

Hearing: At 9 months (or sooner if concerns) and follow-up as needed. Echocardiogram not required annually if normal at diagnosis. Just done PRN after that until adolescent when look for MVP. Thyroid: Screen as newborn, 6 months, 12 months, then annually up to age 18. Leukemia screening. Cervical spine for atlantoaxial instability at 3-5 years.

Question 43

. Classic facial features for Down Syndrome

Answer 43

Protruding tongue, flat nasal bridge, small ears, low set ears epicanthal folds, Brushfield spots, palmar folds.

Question 44

Differential diagnoses for Down Syndrome

Answer 44

Turner syndrome has webbed neck, broad chest, low hairline, short stature, delayed puberty. Lack of X chromosome. Klinefelter Syndrome: Delayed puberty, scoliosis, long arms, decreased testicular size, small penis, gynecomastia, taller. No facial features. No webbed neck. XXY. Extra X chromosome. Trisomy 18 (Edward Syndrome): Cleft lip, no webbed neck, smaller head, cleft palate. Noonan Syndrome: Webbed neck. No classic facial features like with Trisomy 21.

Question 45

In newborn exam: look for major and minor _______ and also assess for _______ ________

Answer 45

Anomalies, dysmorphic features

Question 46

Minor anomalies are

Answer 46

more cosmetic (extra digit, hair whorl).

Question 47

Major anomalies

Answer 47

impair major body function: congenital disease, cleft palate.

Question 48

In terms of anomalies, when to refer for genetic testing?

Answer 48

3 or more minor, 2 major, or 1 major + 2 minor

Question 49

Dysmorphic features

Answer 49

malformation (result from intrinsic process producing basic alterations in structure—cleft lip, cleft palate) vs deformation (external process—club foot, molding).

Question 50

Most common dysmorphic feature (not a major or minor malformation)

Answer 50

Club foot (Talipes Equinovarus). The feet are turned downward and inward, and the sole is directed medially.

Question 51

Types of anomalies

Answer 51

o Deformation: Abnormal shape or position of body part caused by external mechanical forces.
o Disruption: Defect of organ or large body part caused by external disruption of normal process.
o Dysplasia: Abnormal organization of cells into tissues.
o Malformation: Abnormal development of an organ or large body part from an intrinsically abnormal process.

Question 52

In looking at umbilical cord, expect to see 2______ and 1_____

Answer 52

2 arteries and 1 vein. Other numbers can be associated with genetic anomalies.

Question 53

Reasons to refer for genetic testing

Answer 53

Growth is not right (short stature), really tall or short for age, muscle tone is hypotonia, muscle weakness, nothing obvious but there are developmental delays.

Question 54

Meconium not passed after 48 hours

Answer 54

If not, consider cystic fibrosis. Look for intestinal obstruction, bowel obstruction.

Question 55

Meconium is normally passed within

Answer 55

24 hours. 100% should by 48 hours.

Question 56

Meconium is

Answer 56

black and sticky like tar, first 24-48 hours

Question 57

Transition stool is

Answer 57

brownish-green color, occur day 2-3

Question 58

Breastfed stool looks

Answer 58

yellow and seedy and more liquidy and more stools if breastfed.

Question 59

Formula fed stool looks

Answer 59

more firm, larger curds and greener brown

Question 60

Autosomal recessive

Answer 60

Carriers have 1 chromosome. Takes 2 chromosomes to have the disease. Must have 2 copies of mutated gene: 1 from each parent. If both parents carry gene mutation: 25% chance of getting the disorder. 50% chance of getting 1 copy and being carrier. 25% of not inheriting either copy of gene mutation. Example: Cystic fibrosis.

Question 61

Autosomal dominant

Answer 61

Only need 1 gene mutation to have disease. 50% risk if 1 parent has gene mutation. 50% risk for recurrence. Doesn’t skip generations. Equal for male and female. Passes from only 1 parent. Examples: Huntingdon’s disease, Noonan’s syndrome, Marfan’s syndrome, neurofibromatosis.

Question 62

X-linked

Answer 62

Can never be passed from father to son. Males can’t be carriers and will always be affected if mother is a carrier. Females pass it to son. Daughters can inherit from father, but fathers can’t pass it to sons. So, for a woman to be a carrier, her father must have the condition. Example: Hemophilia.