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98 Cards in this Set
- Front
- Back
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What is phenylketonuria?
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Its an autosomal recessive disorder caused by a lack of enzyme phenylalanine hydroxylase. Causes mental retardation.
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What is the treatment for phenylketonuria?
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Diet low in phenylalanine
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Why do people with PKU have light hair and skin?
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Because phenylalanine can't be converted into tyrosine, which is a precursor of melanin
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What is galactosemia?
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An autosomal recessive disorder of galactose metabolism (which is a breakdown product of lactose).
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Which enzyme is required to convert galactose to glucose?
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Galactose-1-phosphate uridyltransferase (GALT), the enzyme responsible for galactosemia
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Which organs suffer the most damage in a galactosemic patient?
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Liver, eyes, and brain.
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T/F Galactosemia is due to a single point mutation of the GALT gene in 70% of cases
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True
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What would cause a doctor to suspect galactosemia?
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Presence of sugars in the urine other than glucose (such as fructose, galactose, lactose, and maltose)
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What is the diagnostic test for galactosemia?
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Tests that identify a deficiency of transferase in leukocytes and erythrocytes
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T/F Lysosomal storage diseases due to missing enzymes are autosomal dominant disorders
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False, autosomal recessive
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How can some lysosomal storage diseases be treated?
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By enzyme replacement therapy
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What is the most common gangliosidosis?
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Tay sachs disease, which is due to a mutation is enzyme hexosaminidase A
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Which ethnic group is most commonly associated with lipidoses (such as Tay sachs)?
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Ashkenazi Jews
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What is Niemann-Pick disease?
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It is a lysosomal storage disease caused by lack of sphingomyelinase. Sphingomyelin accumulates in phagocytic cells and neurons
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What is the most common type of Niemann-Pick disease?
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Type C (category 2) that is due to mutation in the NPC1 protein
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How can Niemann-Picks be diagnosed?
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By estimation of sphinomyelinase activity in leukocytes or cultured fibroblasts
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What is Gaucher disease?
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It is due to mutation in glucocerebrosidase that normally cleaves glucose from ceramide. Glucocerebrosides accumulate in phagocytic cells.
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What are Gaucher cells?
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Enlarged phagocytes due to accumulation of distended lysosomes. Histologically the cytoplasm resembles wrinkled tissue paper.
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Where are Gaucher cells commonly found?
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In liver, spleen, lymph nodes, and bone marrow.
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T/F Type 1 (chronic non-neuronopathic) Gaucher disease accounts for only 1% of cases
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False, it accounts for 99% of cases
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T/F Gaucher disease is an autosomal recessive disease characterized by accumulation of glucocerebrosides in macrophages
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True
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How can Gaucher disease be treated?
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By administration of purified glucocerebrosidase
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How is mucopolysaccharidosis classified?
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There are seven types and each results from deficiency in different enzyme involved in break-down of mucopolysaccharides
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Which mucopolysaccharides accumulate in tissues?
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Dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate
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What are the most common effects of mucopolysaccharidosis?
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Coarse facial features (gargoylism), corneal clouding, joint stiffness, mental retardation, and increased urinary excretion of MPS
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What is Hurler syndrome?
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It is a form of mucopolysaccharidosis
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What is the one mucopolysaccharidosis that isn't autosomal recessive?
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Hunter syndrome, which is X-linked recessive.
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T/F In glycogenoses, the excess glycogen is most often stored in the cytoplasm or nuclei of macrophages
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True, most often in cytoplasm, only sometimes in nucleus
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What are the three categories of glycogen storage diseases?
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Hepatic forms, myopathic forms, and atypical forms
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What is Von Gierke disease?
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Type 1 glycogenosis, the most importnat hepatic form. Due to lack of glucose-6-phosphatase
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What is the effect of myopathic glycogenosis?
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Glycolysis in muscle cells is impaired so there is low energy output. Example is McArdle disease (type 5)
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What is Pompe disease?
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Type 2 glycogenosis due to deficiency in lysosomal acid maltase. Glycogen deposits in almost every organ, especially heart.
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T/F In ~5% of cancers, the mutations affecting tumor suppressor genes are present in all cells of the body and can be passed on
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True
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Is neurofibromatosis recessive or dominant?
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Its autosomal dominant
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Which germ layer derivatives can be affected by neurofibromatosis?
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All three because the tissues affected are of neural crest origin
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T/F Type 2 nuerofibromatosis accounts for 90% of cases
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False, type 1
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What are the 3 main features of NF type 1?
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Multiple neurofibromas, cafe-au-lait spots on the skin, and Lisch nodules
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T/F In ~5% of cancers, the mutations affecting tumor suppressor genes are present in all cells of the body and can be passed on
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True
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Is neurofibromatosis recessive or dominant?
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Its autosomal dominant
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Which germ layer derivatives can be affected by neurofibromatosis?
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All three because the tissues affected are of neural crest origin
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T/F Type 2 nuerofibromatosis accounts for 90% of cases
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False, type 1
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What are the 3 main features of NF type 1?
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Multiple neurofibromas, cafe-au-lait spots on the skin, and Lisch nodules
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Which disease is associated with cafe-au-lait spots?
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Neurofibromatosis type 1. These spots usually overlie a neurofibroma
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What are Lisch nodules?
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They are pigmented iris hamartomas present in type 1 neurofibromatoma. They don't cause problems, but are helpful in diagnosing
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What makes neurofibromatosis a potentially serious condition?
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The fact that benign neurofibromas can transform into a malignancy in some pts
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What is a pheochromocytoma?
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A tumor of the adrenal medulla that results in extreme hypertension
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Which chromosome is the NF1 gene located on?
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Chromosome 17
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What are the characteristics of NF type 2?
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Defining feature is bilateral acoustic schwannomas. Cafe-au-laite spots present but Lisch nodules absent.
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Define multifactorial trait
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A trait governed by the additive effect of two or more genes of small effect-conditioned by environmental, nongenetic influences
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What type of disease is hypertension?
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Multifactorial disease, due in part to effects of multiple genes (and environment)
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What is a karyotype?
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A photographic representation of stained metaphase spread in which chromosomes arranged in order of decreasing length
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What is the most common method of chromosome staining?
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Giemsa stain (G banding) technique which causes chromosomes to have light and dark bands of variable widths.
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T/F Euploid is any exact multiple of haploid number (n)
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True
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What is polyploidy?
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Having chromosome numbers such as 3n or 4n. Generally results in spontaneous abortion. Luckily this rarely occurs
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What is aneuploidy?
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Having any number of chromosomes that is not an exact multiple of haploid number (n). This means a change in part of chromosome set
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What causes aneuploidy?
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Non-disjunction of homologous chromosomes at first meiotic division or failure of sister chromatids to separate during second meiotic division. Leads to n+1 or n-1
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T/F Trisomies of certain autosomes and monosomy of sex chromosome are not compatible with life
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False, only monosomy involving autosomes are incompatible with life
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What is mosaicism?
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The presence of two or more populations of cells in the same individual. This is usually due to postzygotic mitotic non-disjunction involving sex chromosomes
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What is the cytogenetic shorthand used to describe structural changes in a chromosome?
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p (petit) is the short arm and q is the long arm. Each arm is divided into numbered regions from the centromere outward
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What are the patterns of chromosomal rearrangement after breakage?
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Translocation, isochromosomes, deletion, and inversions
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When is translocation most dangerous?
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During gametogenesis when it will cause unbalanced gametes leading to abnormal zygotes
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What is the result of a Robinsonian translocation?
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The carrier has only 45 chromosomes
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What are isochromosomes?
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When a centromere divides horizontally rather than vertically and you get chromosome with two short arms or two long arms
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When would you get a ring chromosome?
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When you get deletion of both terminal ends of a chromosome and the end join
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What is an inversion?
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When two breaks occur in a chromosome and the piece flips 180 deg and reattaches.
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T/F In general, loss of chromosomal material produces more severe defects than does gain of chromosomal material
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True
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T/F Imbalances of sex chromosomes aren't tolerated as well as imbalance in autosomes
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False, tolerated much better if imbalance is in sex chromosomes
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What is the exception to the general rule that chromosomal disorders have low risk of recurrence in siblings?
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Translocation form of down syndrome
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What are the three principal autosomal trisomies?
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21, 18, and 13
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What is Cri duchat syndrome?
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A deletion of short arm on chromosome 5 that results in cat like cry in infants
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What is the most common of the chromosomal disorders?
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Trisomy 21, or down syndrome caused by meiotic non-disjunction
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T/F 1 in 25 live births in women over 45 result in down syndrome
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True, only 1 in 1550 in women under 20
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T/F 95% of cases of trisomy are the result of extra chromosome from the mother
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True, almost never comes from father
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What is responsible for about 40% of childhood deaths in down syndrome pts?
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Cardiac malformations
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What increased cancer risk do down syndrome pts have?
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Development of acute leukemias
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What commonly happens to down syndrome pts that make it to middle age?
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Development of Alzheimers or dementia
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What is the clinical name for 22q11 deletion?
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DiGeorge syndrome. Variation in size and location of deletion can lead to differences in severity
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What is lyonization?
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It is the random inactivation of either paternal or maternal X chromosome in an early zygote
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What is a Barr body?
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It is a clump of chromatin attached to the nuclear membrane in somatic cells of females. Represents the inactivated X chromosome
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What is the result of lyonization?
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Females end up being a mosaic of cells with either maternal or paternal X chromosome activated
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T/F If a zygote gets three X chromosomes and one Y chromosome, they will be female
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False, if they have a Y they will invariably be male
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What is the chromosomal abnormality in Kleinfelter syndrome?
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Most patients are 47, XXY. This results from nondisjunction of sex chromosomes during meiosis.
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What are the clinical features of Kleinfelter syndrome?
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The most common is hypogonadism (small testicles) leading to sterility. Others include longer arms and legs, reduced body hair, and gynocomastia
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What is the chromosomal abnormality in Turner syndrome?
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Either missing part or all of the second X chromosome. Most are missing all so are 45, X.
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What are the clinical characteristics of Turner syndrome?
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Growth retardation, edema of hands and feet, little breast and genitalia development, and high-arched palate
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What secondary hormonal problems can arrise in Turner syndrome pts?
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25-30% of pts have hypothyroidism caused by autoantibodies
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What is the most common karyotype in Turner syndrome?
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Deletion of small arm leading to isochrome of the long arm of second X chromosome
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What are the three groups of diseases resulting from mutations affecting single genes that don't follow mendelian inheritance?
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Triplet repeat mutations, mutations in mitochondrial genes, and genomic imprinting
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What are trinucleotide repeat mutations and what do they cause?
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They are characterized by long repeating sequence of 3 nucleotides. Includes fragile X, Huntington disease, and myotonic dystrophy
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T/F Approx 20% of males who carry fragile X mutation are clinically normal
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True
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What are the clinical manifestations of fragile X?
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Mental retardation is the big one, this is the biggest cause of familial mental retardation. Also long faces, large ears and testicles
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What genetic product is lacking in fragile X pts?
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The FMR1 gene gets hypermethylated and silenced. Its normal products is necessary for normal function of neurons
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What is the net effect of all the trinucleotide repeat diseases?
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They all effect neurodegenerative changes
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What is the inheritance pattern of mitochondrial DNA?
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It is only associated with maternal inheritance because the ova has mitochondria and the sperm doesn't really have many
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T/F Genes that are paternally imprinted are only expressed on the maternal chromosome
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True, works the other way around as well
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What causes Prader-Willi and Angelman syndromes?
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A deletion on one of the long arms of chromosome 15. There is a deficiency due to one missing copy and one copy that is imprinted (silenced).
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What are the clinical characteristics of Prader-Willi syndrome?
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Mental retardation, short stature, hypogonadism, obesity. This is due to deletion on paternal chromosome
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What are the clinical characteristics of Angelman syndrome?
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Mental retardation, ataxia, seizures, and inappropriate laughter (called happy puppet syndrome)
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