Kendall

Question 1

Patients with Marfan should also be screened for ______

Answer 1

homocystinuria

Question 2

What is the most common cause of inherited learning disability?

Answer 2

Fragile X

Question 3

Mutation behind Rett’s syndrome

Answer 3

Loss of function mutations of MECP2 gene on X chromosome

Question 4

Calling card of Rett’s

Answer 4

Girls with normal development until 18 months, at which point they develop microcephaly and skill loss

Question 5

MECP2 is responsible for _____. Mutations would cause _______.

Answer 5

global gene silencing / inappropriate gene activation

Question 6

Metabolic disorders are almost always ______ _______ inheritance, resulting in a _____ recurrence risk for a couple.

Answer 6

Autosomal recessive / 25%

Question 7

What increases the risk of inheriting inborn errors of metabolism?

Answer 7

Consanguinity

Question 8

Abnormal levels of PHE prevent the normal transport of other amino acids, specifically ______, across the ______.

Answer 8

Tyrosine / blood-brain barrier

Question 9

What is the standard treatment for PKU?

Answer 9

Dietary therapy for life

Question 10

What is significantly affected by delays in the initiation of low-PHE diet for PKU patients?

Answer 10

Their IQ

Question 11

New therapy for PKU

Answer 11

Kuvan

Question 12

Galactosemia babies should also be screened for ______

Answer 12

e. coli infection

Question 13

Organs most affected by mito disease

Answer 13

CNS
Muscles
Cardiac
GI system including liver
Kidneys

Question 14

How do you treat Wilson’s disease?

Answer 14

Penicillamine (binds copper and leads to excretion of copper in urine)

Question 15

Mitochondrial genes are responsible for creating proteins that ______

Answer 15

control ETC structure, function, and assembly

Question 16

Mitochondrial disorders are most often inherited from mom/dad/both

Answer 16

Both

Question 17

Before starting mito evaluation, should also screen for….

Answer 17

Chrosomome abnormalities
Other inborn errors of metabolism
Any other disorders that could explain the clinical presentation

Question 18

Functional testing

Answer 18

examines the OXPHOS energy pathway

Question 19

Gene testing

Answer 19

evaluation of mtDNA and nuclear mitochondrial genes

Question 20

Biomarker studies

Answer 20

lactate and pyruvate levels, CSF lactate, CPK, urine organic acids, carnitine levels

Question 21

What percentage of mito disease patients are diagnosed through gene testing?

Answer 21

50-60%

Question 22

Radiographic studies

Answer 22

ID of mito related imaging abnormalities

Question 23

What sort of findings are strongly suggestive of mito energy disorders?

Answer 23

Typical brain changes suggestive of Leigh disease or abnormalities in white matter

Persistent, significant elevations in LACTATE (especially in brain) and other biochemical features

Problems in many body systems suggestive of mito disease

Strong family history of mito disease

Question 24

Calling card of Leigh disease (imaging)

Answer 24

On MRI:

Bilateral, symmetrical basal ganglia lesions

Question 25

What are ragged red fibers?

Answer 25

Common histological finding in mito disease: red fibers are mitochondrial proliferation

Question 26

What percentage of patients are diagnosed via finding ragged red fibers?

Answer 26

2.5% of patients

Question 27

Ragged red fibers are usually found in _____ patients

Answer 27

Adult

Question 28

Approx. how many genes are involved in mito energy production?

Answer 28

1500

Question 29

How many genes does mtDNA sequencing screen?

Answer 29

37 maternally inherited mitochondrial genes

Question 30

MELAS cause

Answer 30

tRNA 3243 mutation | Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke Like Episodes

Question 31

MERRF cause

Answer 31

tRNA 8344 mutation | Myoclonic Epilepsy and Ragged Red Fibers

Question 32

SURF1 mutation

Answer 32

complex IV assembly gene mutations | associated with Leigh disease

Question 33

Complex I nuclear gene mutations associated with what diseases?

Answer 33

Leukodystrophy and myoclonic epilepsy

Question 34

Metabolic abnormalities supportive of mitochondrial disease

Answer 34

Increased blood and/or CSF lactate and pyruvate Decreased plasma carnitine Increased blood alanine Generalized aminoaciduria

Question 35

Inheritance of mitochondrial energy disorders

Answer 35

Autosomal recessive (most common) Autosomal dominant Sporadic X-linked

Question 36

1 in ____ people diagnosed with autism

Answer 36

66

Question 37

Autism 4 times more likely to affect boys/girls

Answer 37

Boys

Question 38

How often is an underlying diagnosis established in autism cases?

Answer 38

2-36%

Question 39

____ out of 100 autism patients also had underlying mito disease

Answer 39

4-7

Question 40

One study found that ____% of autism patients had enzyme function affecting complex I

Answer 40

60

Question 41

Symptoms of HMSN

Answer 41

Slowly progressing muscle weakness and wasting Tremors High arches and curled toes

Question 42

HMSN caused by

Answer 42

Overproduction of PMP-22, which prevents Schwann cell proliferation

Question 43

NF caused by

Answer 43

Mutation of NF1 gene on the long arm of chromosome 17

Question 44

Symptoms of NF

Answer 44

Small pigmented skin lesions (cafe au lait spots) Small soft fleshy benign tumors Large head Lisch nodules

Question 45

1/3 of NF cases result in ______

Answer 45

Non-verbal learning disorder

Question 46

Most NF patients are normal and healthy, but some develop....

Answer 46

Epilepsy CNS tumor Scoliosis

Question 47

Age of onset for NF

Answer 47

<5 years

Question 48

Test used to ID Lisch nodules

Answer 48

Slit-lamp

Question 49

Marfan syndrome cause

Answer 49

Mutation of type 1 fibrillin gene (FBN1)

Question 50

Other conditions associated with HMSN

Answer 50

Charcot-Marie-Tooth | Peripheral Muscular Atrophy

Question 51

Symptoms of Duchenne's

Answer 51

Awkward, clumsy walking Muscle weakness (feet and moves upward) 1/3 have learning disabilities

Question 52

Duchenne's patients typically die because of

Answer 52

Heart failure | Pneumonia

Question 53

Duchenne's is caused by

Answer 53

Deletion of dystrophin gene

Question 54

What biomarker level is markedly elevated in Duchenne's?

Answer 54

CPK (muscle enzyme)

Question 55

Losartan has been shown to halt progression of which conditions?

Answer 55

Marfan | Duchenne's

Question 56

Most concerning neurological signs

Answer 56

Ataxia Altered state of consciousness Developmental regression

Question 57

Neurological syndromes in infants/children can often signal

Answer 57

``` Undiagnosed PKU (may have been missed because of TPN during newborn screening) Homocystinuria ```