metabolic Flashcards
if you have low blood glucose and hepatomegaly, what type of metabolic disorder should you be thinking of
Glycogen storage disease
what are the 4 types of glycogen storage disease
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)
How do you diagnose type I or type III Glycogen storage disease
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
Treatment of type I or type III Glycogen storage disease
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
Hepatic tumors (sometimes malignant) are a threat in adolescence and adult life for this glycogen storage disease
Type I and III
treatment of Type II Glycogen storage disease (Pompe disease)
Enzyme replacement early in life is effective - This disease also includes cardiac and skeletal muscle
deficiency of galactose-1-phosphate uridyltransferase
Galactosemia
what type of genetic disease is Galactosemia
Autosomal recessive
symptoms of Galactosemia
most striking in the neonate when fed milk, exhibits evidence of
Liver failure - hyperbilirubinemia, coag disorders, hypoglycemia
renal tubular function - acidosis, glycosuria, aminoaciduria
cateracts
Galactosemia is on the neonatal newborn screen so why is it still a problem
affected infants may die in the first week of life so you may not get the results fast enough
Affected infants with Galactosemia are at increased risk for
severe neonatal E.Coli sepsis
Impact of Galactosemia on infants, first few years of life, older children and girls
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
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
Diagnosis galactosemia
Treatment for galactosemia
elimination of dietary galactose results in rapid correction of abnormalities, but infants who are extremely ill before treatment may die before therapy is effective
most striking in the neonate when fed milk, exhibits evidence of
Liver failure - hyperbilirubinemia, coag disorders, hypoglycemia
renal tubular function - acidosis, glycosuria, aminoaciduria
cateracts
Galactosemia
symptoms of Galactokinase deficiency
what is the problem
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
symptoms of Hereditary fructose intolerance
what is the deficiency
what is it similar to
TX?
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
what grouping do these disorders fall under?
Glycogen storage diseases
Galactosemia
Galactokinase deficiency
Hereditary fructose intolerance
Carbohydrate Disorders
What types of glycogen storage diseases Affect liver and influence blood sugar
Types I VI, VIII
What types of glycogen storage diseases involve muscles and affect ability to do anaerobic work
Types V, VIII
What types of glycogen storage diseases Affect liver and muscles and influence B.G. and muscle metabolism
Type III
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
Type II and IV
fructose-1-phosphate aldolase deficiency
Hereditary fructose intolerance
This disorder is a result of a defect in the hydroxylation of phenylalanine to form tyrosine
This is a autosomal recessive disease
Phenylketonuria (PKU)
effects of Phenylketonuria (PKU) if not treated after being detected on NB screen and confirmed
primarily affects the brain -
if untreated, severe intellectual disability (IQ 30) develops in the first year of life
Dx Phenylketonuria (PKU)
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
If diagnose with Phenylketonuria (PKU), what should they also be tested for
to see if they have a defect in the synthesis or metabolism of tetrahydrobiopterin
TX for Phenylketonuria (PKU)
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
long term need to know for PKU female patients
planning to get pregnant will require rigorous management prior to conception and throughout pregnancy to prevent fetal brain damage, congenital heart disease and microcephaly
fumarylacetoacetate hydrolase deficiency
Tyrosinemia Type I
symptoms of Tyrosinemia Type I
severe liver disease associated with -bleeding disorder -hypoglycemia -hypoalbuminemia -elevated transaminases Defects in renal tubular function
Hepatocellular carcinoma may eventually occur
severe liver disease associated with -bleeding disorder -hypoglycemia -hypoalbuminemia -elevated transaminases Defects in renal tubular function
Hepatocellular carcinoma may eventually occur
symptoms of Tyrosinemia Type I
Dx of Tyrosinemia Type I
On newborn screen
increased concentration of succinylacetone
DNA testing available
TX of Tyrosinemia Type I
medication:
Nitisinone (NTBC)
effectively eliminates the production of toxic succinylacetone
Low phenylalanine, low tyrosine diet may also play a role
symptoms of Tyrosinemia Type II and Type III
treatment
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
deficiency of cystathionine B synthase
Homocystinuria
symptoms of Homocystinuria
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
what is a constant threat for kids with Homocystinuria
major arterial or venus thromboses are a constant threat
Homocystinuria dx confirmation after newborn screen
demonstration of elevated total homocysteine in the blood
Plasma amino acid profile reveals hypermethioninemia
treatment of Homocystinuria
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
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
Maple Syrup Urine Disease (MSUD)
also known as branched chain ketoaciduria
clinical manifestations of Maple Syrup Urine Disease (MSUD)
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
what metabolic disorder should be strongly suspected in a child with positive urine ketones on a dipstick with no or low B-hydroxybutyrate
Maple syrup urine disease (MSUD)
dx Maple Syrup Urine Disease (MSUD)
showing large increases in plasma leucine with less increases in isoleucine
tx Maple Syrup Urine Disease (MSUD)
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
most feared complication of Maple Syrup Urine Disease (MSUD)
metabolic decompensation leading to brain edema
what type of metabolic disorders are these: PKU Maple Syrup Urine Disease (MSUD) Tyrosinemias homocystinuria
Disorders of amino acid metabolism
