Biochemical Genetics Ii

Front 1

Acute therapy for fatty acid oxidation defects

Back 1

IV fluids with 10% dextrose, maybe with bicarbonate

Front 2

prognosis for untreated LCHAD/VLCHAD

Back 2

potentially fatal acute metabolic crises, heart failure from cardiomyopathy

Front 3

Another name for glutaric acidemia type II

Back 3

MAD deficiency

Front 4

3 clinical types of glutaric acidemia type II

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1. neonatal onset with congenital anomalies
2. neonatal onset without congenital anomalies
3. later onset

Front 5

Enzyme defective in glutaric acidemia type II

Back 5

electron transfer flavoprotein or EFT-DH

Front 6

What effect can fatty acid oxidation disorders have on the brain?

Back 6

encephalopathy

Front 7

Effect of untreated glutaric acidemia type II on neonates

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usually don't survive

Front 8

cofactor needed for glutaric acidemia type II

Back 8

riboflavin

Front 9

Causes of encephalopathy in FAODs

Back 9

metabolic acidosis, hypoglycemia, big fats wandering around can be neurotoxic. But the main cause is the lack of ketones for energy when the sugar runs out. Can lead to coma and death.

Front 10

What ultimately causes symptoms in FAODs?

Back 10

Not hypoglycemia, but lack of ability to have energy from fats. Also, accumulation of fats

Front 11

Clinical features of all FAODs.

Back 11

fasting intolerance, coma, seizure, liver dysfunction

Front 12

Cardiomyopathy occus in which of the FAODs?

Back 12

Mostly in the longer chain FA oxidation disorders and carnitine transport defects

Front 13

Congenital anomalies occur in which of the FAODs?

Back 13

Mostly in severe CPT II deficiency and glutaric acidemia type II

Front 14

What happens to free carnitine in organic acidemias and FAODs?

Back 14

Extra metabolites bind carnitine, so free carnitine is low, and other things are high (acylcarnitines, acylglycines, organic acids)

Front 15

In FAODs, what 3 tests will show abnormalities with respect to carnitine levels?

Back 15

acylcarnitine, acylglycine, organic acids

Front 16

Features of acute fatty liver of pregnancy

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abdominal pain, nausea, voming in 3rd trimester, hypoglycemia, kidney and liver failure, coma, hemorrhage

Front 17

Most common FAOD to cause HELLP or AFLP in pregnant women

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LCHAD

Front 18

Major symptoms of galactosemia

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jaundice, bleding diathesis, feeding problems, irritability, lethargy, sepsis, cataracts

Front 19

long-term complications of galactosemia

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dev. delay, language delay, motor delay, premature ovarian failure, diminished bone density

Front 20

Immediate newborn therapy for galactosemia

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soy formula only, watch for sepsis, treat liver disease

Front 21

Long-term treatment for galactosemia

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lactose-free diet, calcium supplementation, watch bone density and eyes, ovarian function, developmental support

Front 22

Lysosomes are most prevalent in what type of cells?

Back 22

white blood cells

Front 23

Molecules targeted to the lysosomes for breakdown have what added to them?

Back 23

mannose-6-phosphate

Front 24

Name 2 X-linked lysomal storage disorders

Back 24

Hunter, Fabry

Front 25

Organ systems affected by lysosomal storage diseases

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liver, spleen, bones, lungs, brain, kidneys, heart

Front 26

Enzyme missing in Gaucher

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Beta-Glucocerebrosidase A

Front 27

Type of cancer risk for Gaucher

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multiple myeloma

Front 28

Name of the recombinant enzyme used to treat Gaucher

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cerezyme

Front 29

What tissues are aided by enzyme replacement therapy in Gaucher? What tissues can't be helped?

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Soft tissues are improved, bone and brain can't be helped.

Front 30

Skin manifestations of infantile Gaucher

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hydrops fetalis, collodion skin and lamellar ichthyosis

Front 31

Describe Type III Gaucher

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subacute--organ involvement in 1st decade. Then in late childhood, start getting ataxia, paraplegia, dementia, seizures

Front 32

What happens in Fabry disease?

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Males affected--cells that line blood vessels are missing an enzyme, so don't get blood to capillaries properly. Affects gut, kidney, heart, limbs. Stroke, but not cognitive impairment. Extremely painful extremities, always miserable.

Front 33

Eye findings associated with Fabry disease

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Corneal opacity, spoke pattern, vision itself is fine, affects both genders, even female carriers, tortuous vessels in retina

Front 34

Patients with Pompe disease can's tstore what?

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glycogen

Front 35

Systems most affected by Pompe disease

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cardiac and skeletal muscle

Front 36

Name 2 treatments for mucopolysaccharidoses

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bone marrow transplant, enzyme replacement

Front 37

Treatment for a newborn with Hurler syndrome

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bone marrow transplant--source of enzyme that will cross the BBB

Front 38

Gene mutated in Gaucher

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GBA

Front 39

Three subtypes of Gaucher

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non-neuronopathic, infantile acute neuroopathic, subacute nueronopathic

Front 40

Dysmorphic features in Zellweger

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low broad nasal bridge, high forehead, flattened occiput, high arched palate, micrognathia

Front 41

Eye findings in Zellweger

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optic atrophy, cataracts

Front 42

kidney findings in Zellweger

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renal cortical cysts

Front 43

eye findings in infantile Refsum

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RP

Front 44

What percent of female carriers of X-linked ALD will have symptoms?

Back 44

20%

Front 45

If you have a homoplasmic LHON mutation, what is the likelihood that you will go blind, based on gender?

Back 45

males=40% (60% are fine)
females=10%
males are 4X more likely to be affected, no one know why

Front 46

What % of childhood hearing loss is due to mitochondrial mutations?

Back 46

about 5%

Front 47

Mutations in the 12S rRNA (A1555G) of mitochondria may cause what?

Back 47

hearing loss-often multifactorial and environmental-aminoglycosides

Front 48

Name 2 conditions caused by homoplasmic mitochondrial mutations

Back 48

LHON
hearing loss

Front 49

Features of Mohr-Tranebjaerg

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sensorineural deafness
dystonia
dysphagia
blindness
paranoia

Front 50

Gene and inheritance of Mohr-Tranebjaerg

Back 50

DDP1
X-linked
involved in importing proteins into mitochondria

Front 51

Explain how insufficient frataxin causes Friedreich ataxia

Back 51

Frataxin is a mitochondrial iron chaperone that makes iron available to complexes in electron tansport chain. If frataxin is absent, iron overload occurs and mitochondria are dysfunctional.

Front 52

Part of body most affected in Leigh syndrome

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bottom of the brain-basal ganglia, brain stem, cerebellum

Front 53

Causes of Leigh disease

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nuclear-encoded Complex I genes
nuclear-encoded Complex II genes
nuclear-encoded Complex IV genes
mito-encoded Complex V gene
X-linked E1 alpha

Front 54

Leigh disease caused by mutations in nuclear-encoded Complex II genes has what additional phenotype?

Back 54

Leigh plus tumors--paraganglioma and pheochromocytoma

Front 55

Up to 1/3 of cases of Leigh syndrome are due to mutations in what nuclear gene?

Back 55

SURF1-assembly protein

Front 56

T8993G/C-associated Leigh disease--what determines this vs another disease, and what is the other condition?

Back 56

95% or more mutant heteroplasmy=Leigh
70-95% heteroplasmy =NARP (neuropathy, ataxia, and retinitis pigmentosa)

Front 57

2 genes associated with Autosomal Dominant Progressive External Ophthalmoplegia

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ANT-1 (ATP can't leave mitochondria)
Twinkle (mtDNA replication fork can't unwind)

Front 58

Gene and inheritace assoc. with MNGIE

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Thymidine phosphorylase
Usually autosomal recessive
Causes an dexcess of T's in mtDNA pool, resulting in mtDNA deletions

Front 59

Liver failure might be indicative of what type of mitochondrial defect?

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mtDNA depletion

Front 60

How many trinucleotide repeats are supposed to be present in POLG?

Back 60

10

Front 61

Common MERRF mutation

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A8344G

Front 62

Common mutation for maternally-inherited Leigh or NARP

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G8993T or C

Front 63

Standard mtDNA molecular analysis consists of what?

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PCR for 3 mutations: A3243G, A8344G, T8993G/C
Southern blotting for large rearrangements

Front 64

Most likely mode of inheritance for infantile onset, severe mitochondrial disease? Late-onset, less severe?

Back 64

Infantile onset, severe=autosomal recessive
Late-onset, less severe=maternal mtDNA
(many exceptions)

Front 65

Mitochondrial disease should be considered in any patient with 2 or more of what?

Back 65

neuro-muscular-endocrine-renal tubular dysfunctions

Front 66

Why is it so difficult to diagnose mitochondrial disease?

Back 66

Msut get metabolite testing when patietn is stressed
DNA testing often not positive, even when disease is present
May need muscle biopsy

Front 67

Important aspects of treatment for mitochondrial disease

Back 67

increase energy supply, decrease demand
Avoid fasting-can save lives
Anticipate certain symptoms

Front 68

If ammonia can't become urea, it becomes what? Why is this important?

Back 68

glutamine
single most important nitrogen carrier in blood
high glutamine in brain draws in water, causes swelling

Front 69

Non-metabolic conditions included in newborn screening, as recommended by ACMG

Back 69

cystic fibrosis
hearing
hemoglobinopathies
hypothyroidism
CAH

Front 70

Name some lysosomal storage disorders

Back 70

Krabbe
MPS
Gaucher
Niemann-Pick
Tay Sachs
Fabry
Pompe
Sandhoff

Front 71

Sign of metabolic crisis in urine test, which is found in some organic acidopathies

Back 71

ketonuria

Front 72

Cure for MSUD

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liver transplant

Front 73

Gene assoc. with LCHAD

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HADHA

Front 74

Most common presentation of MCAD

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hypoketotic hypoglycemia

Front 75

Daily treatment for MCAD

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uncooked cornstarch at bedtime to prevent fasting

Front 76

Common symptoms of SCAD

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hypotonia, DD

Front 77

Incidence of PKU

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1:4000 in Ireland and Turkey
1:10,000-15,000 in USA

Front 78

Incidence of galactosemia

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1:60,000

Front 79

Incidence of heterozygotes for familial hypercholesterolemia

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1:500, but not all show signs

Front 80

Features of X-linked chondrodysplasia punctata

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rhizomelic shortening
postaxial polydactyly
sparse hair
cataracts
contractures
red flaky lesions on skin

Front 81

2 syndromes assoc. with the EBP gene

Back 81

X-linked chondrodysplasia punctata
CHILD

Front 82

Incidence of X-linked ALD

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1 in 42,000 males

Front 83

What chemical is deficient in the brain in peroxisomal disorders, and should be given as a daily supplement?

Back 83

DHA

Front 84

What accumulates in Fabry disease?

Back 84

glycosphingolipids

Front 85

What X-linked lysosomal disorder affects males AND females

Back 85

Fabry--female carriers display spectrum of phenotypes