Flashcards in Week 10 Deck (62):
Ashkenazi Jewish decent are higher risk for
Gaucher, Tay-Sachs, Canavan
Mediterraneans are higher risk for
French-Canadians are higher risk for
Tay-Sachs, Branched-Chain Ketoaciduria
Northern Europeans are at higher risk for
CF and PKU
West Africans at greater risk for
Sickle cell and sickle cell-hemoglobin C
Deficiency of galactose-1-phosphate urindyltransferase enzyme that converts galactose to glucose in the digestion of lactose.
Glactosemia Signs and Symptoms
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.
Glactosemia Basic Treatment
Lifelong dietary restriction of lactose. Aggressive surveillance and treatment of sepsis.
Maple Syrup Urine Disease (MSUD) Inheritance
Rare autosomal recessive trait
Maple Syrup Urine Disease (MSUD) Definition/Patho
Elevated serum levels of leucine, isoleucine, valine, and their corresponding ketoacids.
Maple Syrup Urine Disease (MSUD) S/S
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.
Maple Syrup Urine Disease (MSUD) Treatment
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.
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
Apparent at 3 months- vomiting, feeding difficulties, irritability, infantile eczema, hypopigmentation of skin and hair, musty odor urine.
Phenylalanine-restricted diet, <15-20mg/dL
Sickle Cell (hemoglobinopathies) Inheritance
Autosomal recessive sickle gene carried by about 10% of African-Americans in the U.S.
Sickle Cell S/S
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.
Sickle Cell Treatment
Treatment is primarily symptomatic, and includes restoration of intravascular volume, RBC transfusions, splenectomy, prophylactic antibiotics, and pneumococcal vaccination.
Congenital Adrenal Hyperplasia Inheritance
Congenital Adrenal Hyperplasia Definition
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.
Congenital Adrenal Hyperplasia S/S
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.
Congenital Adrenal Hyperplasia Treatment
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.
Medium Chain Acyl-Coenzyme A dehydrogenase Deficiency (MCAD) Inheritance
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.
Fasting/ stress/ illness lead to hypoketotic hypoglycemia, hypotonia, muscle weakness, lethargy, and vomiting progressing to seizures, coma, encephalopathy and death.
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.
When do they normally do newborn screening test?
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).
How is newborn screening test done?
Done by heel stick blood sample.
All states screen for
PKU, galactosemia, and congenital hypothyroidism.
Start treatment _________for galactosemia or maple syrup urine while waiting for confirmation since they can be life threatening.
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.
Maple Syrup Urine Disorder
**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.
**Musty smell to urine caused by PKU. Skin change of eczema.** Treatment: Well-controlled phenylalanine-restricted diet for classical PKU (specialized formula, ongoing adjustments).
Differentiation between Maple Syrup and PKU is
the smell to urine. Maple syrup is sweet and PKU is musty.
Congenital Adrenal Hyperplasia
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.
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.
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.
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.**
Down Syndrome/Trisomy 21 S/S
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.
Down Syndrome/Trisomy 21 Screenings
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.
. Classic facial features for Down Syndrome
Protruding tongue, flat nasal bridge, small ears, low set ears epicanthal folds, Brushfield spots, palmar folds.
Differential diagnoses for Down Syndrome
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.
In newborn exam: look for major and minor _______ and also assess for _______ ________
Anomalies, dysmorphic features
Minor anomalies are
more cosmetic (extra digit, hair whorl).
impair major body function: congenital disease, cleft palate.
In terms of anomalies, when to refer for genetic testing?
3 or more minor, 2 major, or 1 major + 2 minor
malformation (result from intrinsic process producing basic alterations in structure—cleft lip, cleft palate) vs deformation (external process—club foot, molding).
Most common dysmorphic feature (not a major or minor malformation)
Club foot (Talipes Equinovarus). The feet are turned downward and inward, and the sole is directed medially.
Types of anomalies
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.
In looking at umbilical cord, expect to see 2______ and 1_____
2 arteries and 1 vein. Other numbers can be associated with genetic anomalies.
**Reasons to refer for genetic testing**
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.
Meconium not passed after 48 hours
If not, consider cystic fibrosis. Look for intestinal obstruction, bowel obstruction.
Meconium is normally passed within
24 hours. 100% should by 48 hours.
black and sticky like tar, first 24-48 hours
Transition stool is
brownish-green color, occur day 2-3
Breastfed stool looks
yellow and seedy and more liquidy and more stools if breastfed.
Formula fed stool looks
more firm, larger curds and greener brown
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.
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.