METABOLIC & ENDO

Question 1

Inborn errors of metabolism or inherited metabolic disorders

Answer 1

• single gene mutation
• ateration of primary proteni
• compromised or abolished
• disease states

Question 2

is a common finding in a variety of inborn
errors of metabolism

Answer 2

Hepatomegaly

Question 3

An inborn error of metabolism should be considered in any child with 1 or more of the following manifestations:

Answer 3

• Unexplained intellectual disability developmental delay or regression motor deficits or adventitious movements (e.g. dystonia, choreoathetosis) convulsions, unusual odor (particularly during an acute illness)
• Intermittent episodes of unexplained vomiting acidosis, mental deterioration, psychotic behavior or coma
• Hepatomegaly, renal stones, muscle weakness, cardiomyopathy

Question 4

The majority of patients with genetic disorders of
metabolism respond to 1 or all of the following
treatments:

Answer 4

• Special diets: plays an important role
• Hemodialysis: removal of accumulated noxious compounds
• Catabolic states in patients at risk for metabolic crisis
• Administration of the deficient metabolite
• Administration of the cofactor or coenzyme
• Activation of alternate pathways to reduce the noxious compounds
• Administration of the deficient enzyme
• Bone marrow transplantation
• Liver transplantation

Question 5

modalities have the potential to cure the metabolic abnormalities

Answer 5

The bone marrow and liver transplantation

Question 6

• Has the most severe clinical manifestations
• Affected infants who are normal at birth develop
  > poor feeding and vomiting in the 1%t week of life
  > Lethargy and coma may ensue within a few days
• Physical examination reveals:
  > Hypertonicity
  > Muscular rigidity
  > Severe opisthotonus
  > Hypoglycemia
  > Cerebral edema may be present
  > convulsions occur in most infants
  > Death usually occurs in untreated patients in the first few weeks o months of life

Answer 6

Classic Maple Syrup Urine Disease

Question 7

Classical Maple Syrup Urine Disease Diagnosis confirmed by

Answer 7

• marked elevations in plasma levels of leucine, isoleucine, valine, and alloisoleucine (a stereoisomer of isoleucine not normally found in blood) and depression of alanine
• Leucine levels are usually higher than those of the other 3 amino acids
• Urine contains high levels of leucine, isoleucine, and valine and their respective ketoacids

Question 8

MSUD, The enzyme activity can be measured in

Answer 8

• leukocytes
• cultured fibroblasts

Question 9

Treatment of the acute state MSUD

Answer 9

• hydration and rapid removal of the branched-chain amino acids
• Hemodialysis: most effective
• mannitol, diuretics: if cerebral edema (+)

Question 10

• All forms are inherited as an autosomal recessive trait
• Mutations in genes for Ela (45%) and E18 (35%) account for approximately 80% of cases
• the infant may be quite sick by the time the results of the screening becomes available

Answer 10

MSUD

Question 11

• Inherited as autosomal recessive traits
• Prenatal diagnosis
  > Is possible using specific genetic probes in cells obtained from biopsy of the chorionic villi
• Unpleasant odor of phenylacetic acid, which has been described as musty or mousey

Answer 11

Classic Phenylketonuria

Question 12

• Very high plasma concentrations (>20 mg/dL or >1,200 pmole/L)
• Plasma concentrations >20 mg/dL, excess phenylalanine is metabolized to phenylketones (phenylpyruvate and phenylacetate) that are excreted in the urine
• Their presence in the body fluids simply signifies the severity of the condition

Answer 12

Classic phenylketonuria

Question 13

Mildly elevated levels (2-10 mg/dL or 120-600 pmole/L)

Answer 13

Mild hyperphenylalaninemia

Question 14

• (plasma phenylalanine levels >20 mg/dL)
• Affected infant is normal at birth
• Profound intellectual disability develops gradually if the infant remains untreated
• In untreated patients
  > 50-70% will have an IQ below 35, and 88-90% will have an IQ below 65
  > Only 2-5% of untreated patients will have normal intelligence
  > Older untreated children become hyperactive
  with autistic behaviors, including purposeless hand movements, rhythmic rocking, and athetosis
  > Microcephaly, prominent maxillae with widely spaced teeth, enamel hypoplasia, and growth retardation

Answer 14

Severe hyperphenylalaninemia

Question 15

blood for screening for PKU be obtained in the

Answer 15

first 24-48 hr of life after feeding protein

Question 16

PKU is confirmed by measurement of

Answer 16

plasma phenylalanine concentration (may rise 4hr after birth)

Question 17

Mainstay of treatment of PKU is

Answer 17

low-phenylalanine diet

• Maintenance of lower plasma phenylalanine levels (2-10 mg/dL) has been strongly encouraged even after 12 yrs of age.

Question 18

• denotes the elevated level of galactose in the blood
• Two forms of the deficiency exist:
  > infants with complete or near complete deficiency of the enzyme (classic)
  > partial transferase deficiency

Answer 18

Galactosemia

Question 19

• onset of symptoms typically by the second half of the 1st wk of life.
• incidence is predicted to be 1 in 60,000 live births
• newborn infant receives high amounts of lactose (up to 40% in breast milk and certain formulas), which consists of equal parts of glucose and galactose

Answer 19

Classic galactosemia

Question 20

• unable to metabolize galactose-1-phosphate
• the accumulation of which results in injury to kidney, liver, and brain
• diagnosis considered in newborn or young infants with any of the following features:
  > Jaundice, hepatomegaly, vomiting, hypoglycemia, seizures, lethargy, irritability, feeding difficulties, poor weight gain or failure to regain birth weight, aminoaciduria, nuclear cataracts, vitreous hemorrhage, hepatic failure, liver cirrhosis, ascites, splenomegaly, or intellectual disability
• Symptoms are milder and improve when milk is temporarily withdrawn and replaced by intravenous or lactose-free nutrition
• Increased risk for Escherichia coli neonatal sepsis
  -Pseudotumor cerebri can occur and cause a bulging fontanel
• Death from liver and kidney failure and sepsis may follow within days
• When the diagnosis is not made at birth
  > damage to the liver (cirrhosis) and brain (intellectual disability) becomes increasingly severe and irreversible

Answer 20

Galactose-1-phosphate uridyl transferase deficiency galactosemia

Question 21

• generally asymptomatic
• diagnosed in newborn screening because of moderately elevated blood galactose and/or low transferase activity
• considered for the newborn or young infant who is not thriving or who has any of the preceding findings
• Light and electron microscopy of hepatic tissue
  > reveals fatty infiltration, the formation of pseudoacini, and eventual macronodular cirrhosis

Answer 21

Partial transferase deficiency G1PUTDG

Question 22

made by demonstrating a reducing substance in several urine specimens collected while the patient is receiving human milk, cow’s milk, or any other formula containing lactose

Answer 22

preliminary diagnosis of galactosemia

Question 23

• Are usually negative
• test materials rely on the action of glucose oxidase, which is specific for glucose and is nonreactive with galactose

Answer 23

Clinistix urine test results

Question 24

• establishes the diagnosis
• confirm that the patient did not receive a blood transfusion before the collection of the blood sample, as a diagnosis could be missed

Answer 24

Direct enzyme assay using erythrocytes

Question 25

accurately detect levels of galactose-1-phosphate uridyl transferase in erythrocytes

Answer 25

Nonradioactive UV and high-performance liquid
chromatography

Question 26

Tx for Galactosemia

Answer 26

Elimination of galactose from the diet along with adequate calcium supplementation

Question 27

is reported in 80% to more than 90% of female patients with classic galactosemia

Answer 27

Hypergonadotrophic hypogonadism

Question 28

• principal metabolites accumulated are
  galactose and galactitol
• Cataracts are usually the sole manifestation
• pseudotumor cerebri is a rare complication
• otherwise asymptomatic
• Heterozygote carriers may be at risk for presenile cataracts
• diagnosis is made by demonstrating an absence of galactokinase activity in erythrocytes or fibroblasts
• Transferase activity is normal
• Treatment is dietary restriction of galactose

Answer 28

Galactokinase Deficiency Galactosemia

Question 29

• the most frequent disease involving enzymes of the hexose monophosphate pathway
• responsible for 2 clinical syndromes:
  1. episodic hemolytic anemia
  2. chronic nonspherocytic hemolytic anemia
• Most common manifestations
• neonatal jaundice and episodic acute hemolytic anemia
• induced by infections, certain drugs, and, rarely, fava beans
• X-linked deficiency

Answer 29

G6PD Deficiency

Question 30

• provides protection against oxidant threats from certain drugs and infections
• otherwise cause precipitation of hemoglobin (Heinz bodies) or damage the RBC membrane

Answer 30

Reduced GSH

Question 31

• Most cases of are not hereditary and result from thyroid dysgenesis
• Most infants are detected by newborn screening
  programs in the 1st few wk after birth
• before obvious clinical symptoms and signs develop

Answer 31

Congenital HYpothyroidism

Question 32

• (aplasia, hypoplasia, or an ectopic gland) is the most common cause of permanent congenital hypothyroidism
• accounting for 80-85% of cases
• approximately 33% of cases of dysgenesis, even sensitive radionuclide scans can find no remnants of thyroid tissue (aplasia)
• other 66% of infants, rudiments of thyroid tissue are found in an ectopic location, anywhere from the base of the tongue (lingual thyroid) to the normal position in the neck (hypoplasia)
• 2:1female: male ratio
• cause is unknown in most cases
• occurs sporadically, but familial cases occasionally have been reporte

Answer 32

Thyroid Dysgenesis: Primary

Question 33

• most common of the thyroxine (T4) synthetic defects
• marked “discharge” of thyroid radioactivity when perchlorate or thiocyanate is administered 2 hr after administration of a test dose of radioiodine

Answer 33

Thyroid Peroxidase Defects of Organification and
Coupling

Question 34

• autosomal recessive disorder
• caused by a mutation in the chloride—iodide transport protein common to the thyroid gland and the cochlea
• comprised of sensorineural deafness and goiter most common cause of syndromic deafness
• mutation in the pendrin gene have impaired iodide
  organification and a positive perchlorate discharge

Answer 34

Pendred syndrome

Question 35

• a family of autosomal recessive disorders of cortisol biosynthesis
• Cortisol deficiency increases secretion of corticotropin (adrenocorticotropic hormone [ACTH]), which, in turn, leads to adrenocortical hyperplasia and overproduction of intermediate metabolites

Answer 35

COngenital Adrenal Hyperplasia

Question 36

affected fetuses by 8-10 wk of gestation and leads to
abnormal genital development | in females

Answer 36

Prenatal Androgen Excess (CAH)

Question 37

Blood levels of CAH

Answer 37

17-hydroxyprogesterone are markedly elevated

• Diagnosis is most reliably established by measuring 17- hydroxyprogesterone before and 30 or 60 min after an intravenous bolus of 0.125-0.25 mg of cosyntropin (ACTH 1-24)

Question 38

Mothers with pregnancies at risk for CAH are given

Answer 38

dexamethasone, in an amount of 20 ug/kg
prepregnancy maternal weight daily in 2 or 3 divided doses