one who carries two different mutant alleles of the same gene.
Individuals with the Z/Z genotype have only ____ α1-AT activity and account for most cases of the disease.
10-15% of normal
delivering human SERPINA1 to the pulmonary epithelium
Most PKU cases are caused by defects in the _____ encoding phenylalanine hydroxylase.
ATD carrier frequency?
____, relevant to ATD, is made in the liver and secreted into plasma.
α1-antitrypsin (ATT or SERPINA1)
The β subunit gene HEXB resides on chromosome ___.
Most PKU patients are ____ (i.e. having two different mutant alleles of the PAH gene).
What is the frequency of T-S in the general population?
HexA is a heterodimer of ___, which are encoded by the HEXA and HEXB genes, respectively.
Phenylketonuria (PKU) phenotype
Microcephaly; possible profound mental retardation;. seizures, tremors, and gait disorders
Most ATD diseases are associated with two mutant alleles, the ___ and ___ alleles.
Z and S
findings in PKU: urine and sweat
High levels of phenylalanine metabolites and "mousy" odor
Elastase can destroy the connective tissue proteins (particularly elastin) of the lung, causing _____ and ______.
alveolar wall damage; emphysema
Other high-risk groups for T-S are ____, _____, and _____.
certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana
What does T-S disease destroy?
neurons in the brain and spinal cord
Although HexA is a ubiquitous enzyme, the impact of T-S is primarily in the ____ where most of GM2 ganglioside is synthesized.
the existence of multiple mutant alleles of a single gene
PKU carrier frequency
α1-antitrypsin (ATT or SERPINA1) is made in the ____ and secreted into ____.
plasma findings in PKU
High phenylalanine and low tyrosine levels
What is the frequency of T-S in the Ashkenazic Jewish population?
_____ patients have defects in both Hexosaminidase A and Hexosaminidase B (HexB).
Sandhoff disease is caused by a defective ___ subunit; both ____ and ____ activities are affected.
β; HexA and HexB
Although HexA is a ubiquitous enzyme, the impact of T-S is primarily in the brain where most of _____ is synthesized.
a population with higher-than-expected risk for a particular AR disease
_____ can destroy the connective tissue proteins (particularly elastin) of the lung, causing alveolar wall damage and emphysema.
Elastase can destroy the ______ , causing alveolar wall damage and emphysema
connective tissue proteins (particularly elastin) of the lung
Tay-Sachs disease (GM2 gangliosidosis type I)
Inability to degrade ______ results in up to 300-fold accumulation of this sphingolipid inside swollen lysosomes in neurons of the central nervous system.
ATD disease frequency?
The main target of _____ is elastase.
What is the cofactor of PAH?
Elastase is released by _____ in the lung.
ATD patients have a 20-fold increased risk of developing _____.
Defective _____ needed for metabolizing GM2 is responsible for T-S.
hexosaminidase A (HexA)
Z/S compound heterozygotes have ____ α1-AT activity and may develop emphysema.
30-35 % of normal
frequency of PKU
______ is released by neutrophils in the lung.
_____ presents the same neurological symptoms as T-S.
Sandhoff disease (GM2 gangliosidosis type II)
An eye abnormality called ____ is a characteristic of T-S
The ____ in PKU damages the developing central nervous system in early childhood and interferes with the function of the mature brain
high phenylalanine level
Individuals with ___ genotype have 50-60% of normal α1-AT activity and usually do not express disease symptoms.
The most common mutant allele in T-S is _____.
a 4 bp insertion in exon 11 of HEXA
parents sharing one or more common ancestors.
The α subunit gene HEXA resides on chromosome ___.
In ATD, the ___ allele (Glu264Val) expresses an unstable protein that is less effective.
The PAH gene encodes phenylalanine hydroxylase, a liver enzyme that catalyzes the conversion of ____ using molecular oxygen and a cofactor tetrahydrobiopterin (BH4).
Phe to Tyr
In ATD, the ___ allele (Glu342Lys) encodes a misfolded protein that aggregates in the endoplasmic reticulum (ER) of liver cells, causing damage to the liver in addition to the lung.
The SERPINA1 gene is on chromosome ___.
HexA and HexB refer to the two _____; HEXA and HEXB refer to two ____.
___ compound heterozygotes have 30-35 % of normal α1-AT activity and may develop emphysema.
Why does smoking accelerate the onset of emphysema in ATD pts?
Tobacco smoke damages the lung-- more neutrophils to the lung for protection-- More neutrophils release more elastase-- more severe lung damage
Individuals with S/S genotype have ____ α1-AT activity and usually do not express disease symptoms.
50-60% of normal
T-S is caused by a defective ___ subunit; only ___ activity is affected.
The main target of SERPINA1 is _____.
Which chromosome is the PAH gene located at?
Many ATD patients also develop ____ and have an increased risk of ____ due to the accumulation of a misfolded α1-AT mutant protein in the liver.
liver cirrhosis; carcinoma
Individuals with the ___ genotype have only 10-15% of normal α1-AT activity and account for most cases of the disease.
What screening test is used for ATD?
Sequence specific oligonucleotide probes
The PAH gene encodes ____, a liver enzyme that catalyzes the conversion of Phe to Tyr using molecular oxygen and a cofactor tetrahydrobiopterin (BH4).
Defective hexosaminidase A (HexA) needed for metabolizing ___ is responsible for T-S.
1) low-phenylalanine diet 2) oral BH4, supplements
Inability to degrade GM2 ganglioside results in up to 300-fold accumulation of this sphingolipid inside swollen _____ in neurons of the central nervous system.
Hex B is a homodimer of ____.