metabolic

Question 1

if you have low blood glucose and hepatomegaly, what type of metabolic disorder should you be thinking of

Answer 1

Glycogen storage disease

Question 2

what are the 4 types of glycogen storage disease

Answer 2

1) Affect liver and influence blood sugar (I VI, VIII)
2) involve muscles and affect ability to do anaerobic work (V, VIII)
3) Affect liver and muscles and influence B.G. and muscle metabolism (III)
4) Affect various tissues but have no direct effect on blood glucose or on the ability to do anaerobic work (II and IV)

Question 3

How do you diagnose type I or type III Glycogen storage disease

Answer 3

Remember Type I - effects liver and influences blood sugar

Type III - affects liver and muscles and influences B.G and muscle metabolism

increased Serum uric acid
increased Serum lactate
increased Serum triglycerides

confirmed by DNA testing

if inconclusive - enzyme measurements in tissue from affected organ to confirm dx

Question 4

Treatment of type I or type III Glycogen storage disease

Answer 4

maintain Blood glucose or supply alternate energy sources to the muscle

In type I (glucose-6-phosphatase deficiency) usually requires nocturnal intragastric feedings of glucose during the first 1-2 yrs of life then usually snacks and uncooked cornstarch may be satisfactory.

There is no specific treatment for the diseases of muscle that impair skeletal muscle ischemic exercise

Question 5

Hepatic tumors (sometimes malignant) are a threat in adolescence and adult life for this glycogen storage disease

Answer 5

Type I and III

Question 6

treatment of Type II Glycogen storage disease (Pompe disease)

Answer 6

Enzyme replacement early in life is effective - This disease also includes cardiac and skeletal muscle

Question 7

deficiency of galactose-1-phosphate uridyltransferase

Answer 7

Galactosemia

Question 8

what type of genetic disease is Galactosemia

Answer 8

Autosomal recessive

Question 9

symptoms of Galactosemia

Answer 9

most striking in the neonate when fed milk, exhibits evidence of
Liver failure - hyperbilirubinemia, coag disorders, hypoglycemia

renal tubular function - acidosis, glycosuria, aminoaciduria

cateracts

Question 10

Galactosemia is on the neonatal newborn screen so why is it still a problem

Answer 10

affected infants may die in the first week of life so you may not get the results fast enough

Question 11

Affected infants with Galactosemia are at increased risk for

Answer 11

severe neonatal E.Coli sepsis

Question 12

Impact of Galactosemia on infants, first few years of life, older children and girls

Answer 12

infants may die the first week of life

major effects on liver and kidney function and development of cataracts for first few years of life

older children may have learning disorders despite dietary compliance

Girls may develop premature ovarian failure despite treatment

Question 13

Newborn screen

confirmed by lab manifestations

when galactose is ingested as lactose, levels of plasma glucose and erythrocyte galactose-1-phosphate are elevated

frequently hypoglycemic and have albuminuria

Galactose frequently present in urine

The diagnosis is made by showing extreme reduction in erythrocyte galactose-1-phosphate uridyltranferase activity

Answer 13

Diagnosis galactosemia

Question 14

Treatment for galactosemia

Answer 14

elimination of dietary galactose results in rapid correction of abnormalities, but infants who are extremely ill before treatment may die before therapy is effective

Question 15

most striking in the neonate when fed milk, exhibits evidence of
Liver failure - hyperbilirubinemia, coag disorders, hypoglycemia

renal tubular function - acidosis, glycosuria, aminoaciduria

cateracts

Answer 15

Galactosemia

Question 16

symptoms of Galactokinase deficiency

what is the problem

Answer 16

cataract formation - if they are homozygous they usually develop cataracts after the neonatal period. If they are heterozygous, they are at risk as adults

ICP (rare)

problem is accumulation of galactose in body

Question 17

symptoms of Hereditary fructose intolerance

what is the deficiency

what is it similar to

TX?

Answer 17

emesis
hypoglycemia
severe liver disease
severe kidney disease
fructosuria

fructose-1-phosphate aldolase

similar to Galactosemia

eliminate fructose and sucrose from diet prevents clinical disease

Question 18

what grouping do these disorders fall under?

Glycogen storage diseases
Galactosemia
Galactokinase deficiency
Hereditary fructose intolerance

Answer 18

Carbohydrate Disorders

Question 19

What types of glycogen storage diseases Affect liver and influence blood sugar

Answer 19

Types I VI, VIII

Question 20

What types of glycogen storage diseases involve muscles and affect ability to do anaerobic work

Answer 20

Types V, VIII

Question 21

What types of glycogen storage diseases Affect liver and muscles and influence B.G. and muscle metabolism

Answer 21

Type III

Question 22

What types of glycogen storage diseases Affect various tissues but have no direct effect on blood glucose or on the ability to do anaerobic work

Answer 22

Type II and IV

Question 23

fructose-1-phosphate aldolase deficiency

Answer 23

Hereditary fructose intolerance

Question 24

This disorder is a result of a defect in the hydroxylation of phenylalanine to form tyrosine

This is a autosomal recessive disease

Answer 24

Phenylketonuria (PKU)

Question 25

effects of Phenylketonuria (PKU) if not treated after being detected on NB screen and confirmed

Answer 25

primarily affects the brain - if untreated, severe intellectual disability (IQ 30) develops in the first year of life

Question 26

Dx Phenylketonuria (PKU)

Answer 26

quantitative plasma amino acid analysis A plasma phenylalanine value of greater than 360 uM (6mg/dL) is consistent with the diagnosis of one of the hyperphenylalaninemias > 600 uM is classic PKU Milder forms lie between 360-600 A significant number of premature infants and a few full term infants have transient elevations in phenylalanine

Question 27

If diagnose with Phenylketonuria (PKU), what should they also be tested for

Answer 27

to see if they have a defect in the synthesis or metabolism of tetrahydrobiopterin

Question 28

TX for Phenylketonuria (PKU)

Answer 28

designed to maintain plasma phenylalanine values in therapeutic range of 120-360 mM using a diet specifically restricted in phenylalanine but otherwise nutritionally complete outcome is excellent who are treated within the first 10 days of life

Question 29

long term need to know for PKU female patients

Answer 29

planning to get pregnant will require rigorous management prior to conception and throughout pregnancy to prevent fetal brain damage, congenital heart disease and microcephaly

Question 30

fumarylacetoacetate hydrolase deficiency

Answer 30

Tyrosinemia Type I

Question 31

symptoms of Tyrosinemia Type I

Answer 31

``` severe liver disease associated with -bleeding disorder -hypoglycemia -hypoalbuminemia -elevated transaminases Defects in renal tubular function ``` Hepatocellular carcinoma may eventually occur

Question 32

``` severe liver disease associated with -bleeding disorder -hypoglycemia -hypoalbuminemia -elevated transaminases Defects in renal tubular function ``` Hepatocellular carcinoma may eventually occur

Answer 32

symptoms of Tyrosinemia Type I

Question 33

Dx of Tyrosinemia Type I

Answer 33

On newborn screen increased concentration of succinylacetone DNA testing available

Question 34

TX of Tyrosinemia Type I

Answer 34

medication: Nitisinone (NTBC) effectively eliminates the production of toxic succinylacetone Low phenylalanine, low tyrosine diet may also play a role

Question 35

symptoms of Tyrosinemia Type II and Type III treatment

Answer 35

milder form that does not produce the succinylacetone Hyperkeratosis of palms and soles keratitis - produces visual disturbances mild cognitive impairment from significant elevation of tyrosine levels phenylalanine and tyrosine restricted diet

Question 36

deficiency of cystathionine B synthase

Answer 36

Homocystinuria

Question 37

symptoms of Homocystinuria

Answer 37

``` syndrome that includes dislocated ocular lenses long, slender extremities malar flushing livedo reticularis Arachnodactyly scoliosis pectus excavatum or carinatum genu valgum Intellectual disability psychiatric illness ``` major arterial or venus thromboses are a constant threat

Question 38

what is a constant threat for kids with Homocystinuria

Answer 38

major arterial or venus thromboses are a constant threat

Question 39

Homocystinuria dx confirmation after newborn screen

Answer 39

demonstration of elevated total homocysteine in the blood Plasma amino acid profile reveals hypermethioninemia

Question 40

treatment of Homocystinuria

Answer 40

There are two forms for the first form large doses of pyridoxine (100-500mg/day) folate supplementation ``` 2nd form Medication betaine (trimethylglycine) B12 supplement folate supplement ```

Question 41

autosomal recessive disease deficiency of the decarboxylase that initiates the degradation of the ketoacid analogs of the 3 branched chain amino acids - leucine, isoleucine and valine

Answer 41

Maple Syrup Urine Disease (MSUD) | also known as branched chain ketoaciduria

Question 42

clinical manifestations of Maple Syrup Urine Disease (MSUD)

Answer 42

occurs 1-4 weeks after birth poor feeding vomiting tachypnea hallmark is profound depression of the central nervous system, associated with alternating hypotonia and hypertonia (extensor spasms) opisthotonos seizures urine may have the odor of maple syrup labs hypoglycemia metabolic acidosis

Question 43

what metabolic disorder should be strongly suspected in a child with positive urine ketones on a dipstick with no or low B-hydroxybutyrate

Answer 43

Maple syrup urine disease (MSUD)

Question 44

dx Maple Syrup Urine Disease (MSUD)

Answer 44

showing large increases in plasma leucine with less increases in isoleucine

Question 45

tx Maple Syrup Urine Disease (MSUD)

Answer 45

adequate calories and protein with restriction of leucine - critical for acute and chronic mgmt ordinary catabolic stress like moderate infection or labor and delivery in a pregnant mom with MSUD can precipitate clinical crisis Liver transplantation effectively treats MSUD

Question 46

most feared complication of Maple Syrup Urine Disease (MSUD)

Answer 46

metabolic decompensation leading to brain edema

Question 47

``` what type of metabolic disorders are these: PKU Maple Syrup Urine Disease (MSUD) Tyrosinemias homocystinuria ```

Answer 47

Disorders of amino acid metabolism