disorders Flashcards
inherited errors of metabolism in w/c there is an enzyme defect or a defect in the membrane transport system of AA
AMINOACIDOPATHIES
Inherited as an autosomal recessive trait
Phenylketonuria
Enzyme absence in phenylketonuria
Phenylalanine hydroxylase
Phenylalaline metabolites
Phenyl pyruvic acid
Phenyl pyruvate (phenylketone)
Phenyllactate acid
High levels of phenylalanine and it’s metabolites can cause
BRAIN PROBLEMS
Phenylketonuria can found in?
URINE and BLOOD
URINE: Mousy Odor
Phenylketonuria
Retarded mental development and with microcephaly
Phenylketonuria
Is not a result of the lack of PAH enzyme.
Hyperphenylalaninemia
The defect is the Deficiency in the enzymes needed for the regeneration and synthesis of tetrahydrobiopterin (BH4).
Hyperphenylalaninemia
Results in elevated blood levels of phenylalanine and deficient production of neurotransmitters from tyrosine and tryptophan.
Hyperphenylalaninemia
Must be identified so that APPROPRIATE treatment of the active cofactor along with the neurotransmitter precursors L-DOPA and 5-OH tryptophan can be initiated.
Hyperphenylalaninemia
In phenylketonuria every STATE screens newborns from at about?
3 days of age
allows early identification and implementation of treatment
Newborn Screening
The goal of PKU treatment is to maintain the blood levels of phenlyalanine between
2 to 10 mg/dL.
In phenylketonuria, avoid?
High protein foods
In phenylketonuria, take?
Calculated amounts of cereals
Starches
Fruits
Vegetables
Milk substitute
First drug to help manage PKU
KUVAN
KUVAN in other term?
sapropterin dihydrochloride
Help reduce phenylalanine levels by increasing the activity of the PAH enzyme
Phenylketonuria
Test perform in phenylketonuria
Guthrie Test
Semiquantitative, bacterial inhibition assay for phenylalanine that uses the ability of phenylalanine to facilitate bacterial growth in a culture medium with an inhibitor.
Guthrie Test
is able to support bacterial growth but the B-2-thienylalanine inhibits bacterial growth
agar gel
Replaced in many areas by newer techniques.
Guthrie Test
Can detect a wider variety of congenital diseases
Tandem Mass Spectrometry, Gas Chromatography/Mass Spectrometry
For the direct measurement of phenylalanine in dried blood filter disks.
Microfluorometric Assay
Yields quantitative results due to infant not being at least 24 hours old
Microfluorometric Assay
Reference method for quantitative serum phenylalanine
High Performance Liquid Chromatography
Inborn metabolic disorder of tyrosine catabolism which is characterized by the excretion of tyrosine and tyrosine catabolites in urine.
Tyrosinemia
Mos severe form of this aminoacidopathy.
Type I tyrosinemia
Type I tyrosinemia is caused by low level of?
Fumarylacetoacetate hydrolase
Failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, distended abdomen, swelling of legs increased predisposition for bleeding
Type I tyrosinemia
It can lead to liver and kidney failure, problems affecting the nervous system, and an increased risk of cirrhosis or liver cancer later in life.
Type I tyrosinemia
Type II tyrosinemia is the deficiency of the enzyme
Tyrosine aminotransferase.
Mental retardation, excessive tearing, photophobia, eye pain, redness ad painful skin lesions of palms and soles of feet
Type II tyrosinemia
Type III tyrosinemia is the deficiency of the enzyme
4- hydroxyphenylpyruvate dioxygenase
Mild mental retardation, seizures periodic loss of balance and coordination
Type III tyrosinemia
prevents formation of maleylacetoacetic acid and fumarylacetoacetic acid w/c can be converted to succinyl acetone
Nitisone (NTBC)
a toxin that damages liver and kidneys
succinyl acetone
Inborn metabolic disease transmitted as an autosomal recessive gene.
Alkaptonuria
Alkaptonuria lack of the enzyme
Homogentisate oxidase
Urine turns BROWNISH-BLACK when it mixes w/ air.
Alkaptonuria
HGA gradually accumulates in connective tissue, causing OCHRONOSIS (pigmentation of tissues), arthritis, dark spots on sclera, deposition of pigments in the cartilages of ear, nose and extremities.
Alkaptonuria
When performing urinalysis, what substances is added to urine, it will turn black.
ferric chloride
Treatment of alkaptonuria shown to decrease buildup of brown pigment in cartilages and slow the development of arthritis
High dose of vitamin C
Maple Syrup Urine Disease (MSUD) results from an absence or greatly reduced activity of the enzyme branched-chain
a- ketoacid decarboxylase
Has Maple Syrup or Burnt Sugar Odor of the urine, breath, and skin.
Maple Syrup Urine Disease (MSUD)
The result of enzyme defect is accumulation of branched-chain AA and their corresponding ketoacids in the blood, urine and CSF.
Maple Syrup Urine Disease (MSUD)
Seem normal at birth but will develop within a week LETHARGY, vomiting, lack of appetite and signs of failure to thrive.
Maple Syrup Urine Disease (MSUD)
Maple Syrup Urine Disease (MSUD) test perform
Modified Gutrie test: B. subtilis and 4- azaleucine as inhibitor. Microfluormetric assay
Isovaleric Acidemia an autosomal recessive metabolic disorder from a deficiency of the enzyme
Isovaleryl-CoA dehydrogenase
Sweaty Feet Odor
Isovaleric Acidemia
SYMPTOMS: Apparent after few days of birth
Failure to thrive
Vomiting
Lethargy seizure
Coma and Death
Some people are asymptomatic
Isovaleric Acidemia
Isovaleric Acidemia test perform
Chromatography.
MS/MS
Isovaleric Acidemia Laboratory results reveal
Metabolic acidosis
Mild to moderate ketonuria
Hyperammonemia
Thrombocytopenia- low platelets
Neutropenia
Homocystinuria is an inherited autosomal recessive disorder of amino acid metabolism that lack of the enzyme
Cystathionine-B synthetase
Osteoporosis
Dislocated lenses in the eye resulting from lack of
cysteine synthesis and mental retardation.
Multisystemic disorders of the connective tissue, muscles, CNS and bone.
Thrombosis resulting from toxicity of homocysteine to the vascular endothelium is it goes untreated.
Homocystinuria
Dietary restriction of methionine as well as high doses of vitamin B6.
Homocystinuria
Trimethylglycine w/ folic acid
Homocystinuria
Test in homocystinuria
Neonatal Screening: Guthrie test w/ L-methionine sulfoximine
High-Performance liquid Chromatography as
confirmatory test: methionine level > than mg/dL.
LC-MS/MS to test for urinary total homocysteine.
Inherited in an autosomal recessive pattern. Belongs to a class of genetic diseases called urea cycle disorders.
Citrullinemia
Type I Citrullinemia metabolic defect caused by the lack of the enzyme
Argininosuccinic acid synthetase
Lack of appetite
Failure to thrive
Vomiting
Lethargy
Seizure
Coma and Death.
Type I Citrullinemia
Caused by a mutation of the gene that would otherwise provide instructions for making the protein citrin.
Type II Citrullinemia
TREATMENT of Type II Citrullinemia
High-caloric,
Protein-restrictive diet
Arginine supplementation
Sodium benzoate
Sodium phenylacetate
Argininosuccinic Aciduria (ASA) is inherited in an autosomal recessive pattern that also belongs to a class of genetic diseases, the urea cycle disorders lack the enzyme
arginosuccinic lyase
Argininosuccinic Aciduria (ASA) treatment
High-calorie.
Protein-restrictive diet; Arginine supplementation.
Administration of Sodium benzoate and Sodium phenylacetate
Inherited autosomal recessive defect. Caused by a defect in the amino acid transport system rather than a metabolic enzyme deficiency.
Cystinuria
SYMPTOMS:
Hematuria
Pain in the side due to kidney pain
UTI
Cystinuria
produces a red-purple color on reaction w/ sulhydryl groups
cyanide nitroprusside
to remove the kidney stone
Percutaneous nephrolithotripsy
