In born errors of amino acid metabolism Flashcards
In born errors of amino acid metabolism give rise to class of diseases known as the __________.
aminoacidopathies
Aminoacidopathies are diseases caused by a ________ determined, ______ abnormality in the _________ of amino acids
genetically
Biochemical
metabolic pathway
Aminoacidopathies account for a negligible portion of neonatal and paediatric diseases
T/F
F
non-negligible portion
Phenylketonuria (PKU) is inherited as ____________ trait and occurs in about 1 in 15,000 births.
An autosomal recessive
Phenylketonuria (PKU)
Two forms have been identified:
_______ and _______
Classic PKU and non classic PKU
Classic Phenylketonurea
The metabolic defect in the classic form of PKU is _________ of the enzyme ________ which catalyzes the conversion of ________ to ________
an absence of activity
phenylalanine hydroxylase (PAH),
phenylalanine to tyrosine
Classic Phenylketonurea
In the absence of phenylalanine hydroxylase (PAH), phenylalanine levels are usually greater than ______ mol/L.
1200
PKU
In the newborn, the upper limit of normal for a phenylalanine level is _____ mol/L (2 mg/dL).
120
High levels of phenylalanine and some of its metabolites—e.g.,________ acid, _________ and ______ acid— can cause significant _____ problems.
phenylpyruvic
phenylpyruvate
phenyllactic
brain
phenylpyruvate, also known as _______
phenylketone
PKU
All of these Metabolites are found in both the ____ and the ______ of a PKU patient, giving the urine a characteristic _______ odour.
blood; urine
musty
PKU
In infants and children with this inherited defect, _________ and _______ occur as a result of the toxic effects on the brain of phenylalanine or its metabolic by products.
retarded mental development and microcephaly
Phenylketonurea: Treatment
Brain damage can be avoided if the disease is detected at _______ and the infant is ____________________.
Also, women with PKU who are untreated during pregnancy almost always have babies who are _______ and _________
At birth
maintained on a diet containing very low levels of phenylalanine
microcephalic; mentally retarded.
Phenylketonurea: Treatment
The fetal effects of maternal PKU are preventable if the mother is __________________________ from __________ through ——-.
maintained on a phenylalanine-restricted diet
before conception
term
Hyperphenylalaninemia cases occur that are not the result of the lack of the PAH enzyme.
T/F
T
Non classic forms of PKU
The defect in these cases is a deficiency in the enzymes needed for the regeneration and synthesis of ____________
tetrahydrobiopterin (BH4).
BH4 is a ______ required for the enzymatic _______ of the aromatic amino acids _______,_______, and ______
cofactor
hydroxylation
phenylalanine, tyrosine, and tryptophan.
Non classic forms of PKU
A deficiency of ____ results in elevated blood levels of phenylalanine and deficient production of _______ from _____ and _____
BH4
neurotransmitters
tyrosine and tryptophan.
Non classic forms of PKU
Cofactor defects account for only ______% of all cases of elevated phenylalanine levels
1–5
New born screening program for PKU
In the US, every state now screens the blood phenylalanine level of all newborns at about _____ of age.
If the screening test is abnormal, other tests are needed to confirm or exclude PKU.
3 days
Newborn screening for PKU allows early identification and implementation of treatment.
T/F
T
The goal of PKU treatment is to maintain the blood level of phenylalanine between ____ and ____ mg/dL (120–600 mol/L)
2 and 10
Dietary treatment of PKU
Some phenylalanine is needed for normal growth, so a diet that has some phenylalanine but in ______ than normal is the recommended treatment.
much lower amounts
Some phenylalanine is needed for normal growth
T/F
T
High-protein foods, such as meat, fish, poultry, eggs, cheese, and milk, are preferred for patients with PKU.
T/F
F
They are avoided
Instead, calculated amounts of cereals, starches, fruits, and vegetables, along with a milk substitute, are usually recommended
Mass spectrometry is an analytical technique that measures the _________ of ______ particles.
mass-to-charge ratio
charged
Mass spectrometry is most generally used to ___________ by generating a ________ representing the masses of the sample’s components.
find the composition of a sample
mass spectrum
Tandem mass spectrometry
The sample in an MS is first _____ and then ______ to form _________ and _______ that are separated according to their mass-to-charge (m/z) ratio;
The sample is then measured by a ____, which gives the ____ of the _______ for each species.
volatilized
ionized
charged molecular ions and fragments
detector; intensity; ion current
components that are standard in all mass spectrometers: the _______,________ ,________ and ______
the sample inlet, ionization source, mass analyzer, and ion detector
In tandem mass spectrometry applications, the detector is a __________
second mass spectrometer
Tandem mass spectrometry
The MS/MS method has a greater sensitivity, detecting lower levels of phenylalanine and allowing for diagnosis of PKU as early as _____________
The first day of life.
Because MS/MS has the ability to detect more than ____ different genetic disorders with a single specimen, this method is replacing the multiple procedures currently used in newborn screening programs.
25
The reference method for quantitative serum phenylalanine is ________________________
high-performance liquid chromatography (HPLC)
Molecular methods
PKU results from multiple independent mutations (more than _____ identified) at the PAH locus.
400
Albinism results from deficiency of ________ in ________ resulting in inability to form the pigment _____.
tyrosinase
melanocytes
melanin
Albinism
It is _____________ disorder
There is reduced ________ of the _____ and _____
an autosomal recessive
pigmentation
Iris and skin.
Albinism
Patients have _______ and increased incidence of certain ____ cancer.
photosensitivity
skin
Albinism
A mutation in the ____ gene causes deficient ______ production.
TYR
tyrosinase
Albinism
Tyrosinase is required for the conversion of ______ to _______ in the pathway for ______ production.
tyrosine to DOPA
melanin
People with albinism have either a partial or complete _________, or ______, in their _____,_____ or ______
lack of pigment
coloring
eyes, skin or hair.
Tyrosinemia
These are inborn metabolic disorders of _________
tyrosine catabolism
Tyrosinemia
They are characterized by the _____ of ______ and ________ in urine.
excretion
tyrosine and tyrosine catabolites
Tyrosinemia
There are ______ types of tyrosinemia, each with distinctive symptoms and caused by the deficiency of a different enzyme.
three
Type ___ tyrosinemia is the most severe form of this aminoacidopathy and is found in about 1 in 100,000 births.
1
Type I tyrosinemia
Type I tyrosinemia is caused by low levels of the enzyme __________, the ____ of ____ enzymes needed to break down tyrosine.
fumarylacetoacetate hydrolase
fifth
Type I tyrosinemia: Clinical features
Symptoms of type I tyrosinemia include ________ , diarrhea, vomiting, ______ , _____-like odor, ______ abdomen, _____ of legs, and increased predisposition for ______.
failure to thrive
jaundice
cabbage; distended; swelling
bleeding
Type I tyrosinemia: Clinical features
Type I tyrosinemia can lead to ____ and ——- organ failure, problems affecting the ____ system, and an increased risk of _____ or ______ later in life.
liver and kidney
nervous
cirrhosis or liver cancer
Type II tyrosinemia is caused by a deficiency of the enzyme _____________
tyrosine aminotransferase.
