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Flashcards in Genetic disorders of Metabolism Deck (35)
1

Phenylketonuria
- what is it
- genetics
- presentation
- dx
- tx

Defect hydroxylation phenylalanine --> tyrosine

AR trait

Nl at birth until buildup toxic metabolites
- mental retardation
- vomiting (projectivle)
- eczematous rash
- musty odor
- fair haired + skinned + blue eyes

Dx
- Blood screening after 48-72 hrs of life after protein intake
- High phenylalanine, normal tyrosine
- Guthrie test to detect metabolic products of phenylalanine in urine

Tx
- diet low in phenyalanine
- eat tyrosine

Complications:
- infants born to moms with uncontrolled PKU --> risk MR, microcephaly, congential heart dz
- high rate of spontaneous abortions
- screen babies for 2-3 days after birth (nl if mom is ok since they have maternal enzymes)

2

Galactosemia
- etiology
- presentation
- dx
- tx

Deficiency of galactose-1-phosphate uridyl transferase
Galactose 1 phosphate accumulates

--> Kidney, liver, brain, injury

AR inherit

Sx: jaundice, vomiting, cataracts, HSM, E. coli sepsis

Dx:
- newborn screening
- reducing substances in urine

Tx:
- galactose elim

3

Ways to remember lysosomal storage diseases

Gaucher and Krabbe are friends
- gluco vs galacto

Taysachs and N-P are friends cause they have cherry red foveas
- but TaysaX lacks heXosaminidase deficiency
- you never PICK your nose with your sphinger (sphingomyelinase deficiency for Neimann pick)
- but your liver is BIG with NP

Fabry likes ACTs = deficiency in a-galactosidase A, accumulates ceramide trihexoside

Metachromatic leukodystrophy like ARYLcs = deficiency in arylfulfatase A, accumulates cerebroside sulfate

FABRY is the only X linked recessive - all other are AR

4

Hepatomegaly

Aseptic necrosis of femur

Bone crises

Xray = erlenmeyer flask appearance of long bones

Gaucher's disease

Autosomal Recessive

Also have gaucher's cells - macrophages looking like crumpled tissue paper

Confirm with absence of glucocerebrosidase in leukocytes, skin fibroblasts, and liver cells

5

Gaucher's disease
- deficiency enzyme
- accumulated substance

Deficiency:
Glucocerebrosidase

Accumulate:
Glucocerebroside

6

Peripheral neuropathy

Developmental delay

Optic atrophy

Globoid cells

Opsithotonus

Krabbe's disease

Autosomal Recessive

7

Krabbe's disease
- deficiency enzyme
- accumulated substance

Deficiency:
Galactocerebrosidase

Accumulate:
Galactocerebroside

8

Progressive neurodegeneration

Hepatosplenomegaly

Cherry red spot on macula

Neimann Pick disease

Autosomal recessive

Also have foam cells

9

Neimann-Pick disease
- deficiency enzyme
- accumulated substance

Deficiency:
Sphingomyelinase

Accumulate:
Sphingomyelin

10

Progressive neurodegeneration

Developmental delay

Cherry red spot on macula

NO hepatosplanomegaly

Tay Sachs disease
Also in sandoff disease

Autosomal recessive

Also have lysosomes w/ onion skin

11

Tay Sachs disease
- deficiency enzyme
- accumulated substance

Deficiency:
Hexosaminidase A

Accumulates:
GM2 ganglioside

12

Peripheral neuropathy of hands/feet

Angiokeratomas

Cardio/renal disease

Fabry's disease

X linked recessive

13

Fabry's disease
- deficiency enzyme
- accumulated substance

Deficiency:
a-galactosidase A

Accumulate:
Ceramide trihexoside

14

Central and peripheral demyelination w/ ataxia

Dementia

Metachoromatic leukodystrophy

Autosomal recessive

- neurodegen disorder of white matter
- problems with myelin metabolism

15

Metchromatic leukodystrophy
- deficiency enzyme
- accumulated substance

Deficiency:
Arylsulfatase

Accumulate:
Cerebroside sulfate

16

Developmental delay

Gargoylism

Airway obstruction

Corneal clouding

HSM

Hurler's syndrome

Autosomal recessive

17

Hurler's syndrome
- deficiency enzyme
- accumulated substance

Deficiency:
a-L-iduronidase

Accumulate:
Heparan sulfate
Dermatan sulfate

18

Aggressive behavior

NO corneal clouding

Mild:
Developmental delay
Gargoylism

Hunter's syndrome

X linked recessive

You can't have corneal clouding to see as a HUNTER as you aim for the X

19

Hunter's syndrome
- deficiency enzyme
- accumulated substance

Deficiency:
Iduronate sulfatase

Accumulate:
Heparan sulfate
Dermatan sulfate

20

Carnitine deficiency

Inability to transport long chain fatty acids into mitochondria to get broken down

Causes:
- weakness
- hypotonia
- hypoketotic hypoglycemia

21

Alkaptonuria

Autosomal recessive

Congenital deficiency of homogentisic acid oxidase

Can't degrade tyrosine --> fumarate

Benign disease

Findings:
- dark connective tissue
- brown pigmented sclera
- urine turns black on prolonged exposure to air
- can have arthritis --> hoomogentisic acid toxic to cartilage

22

Essential fructosuria

AR

Defect in fructokinase

Benign, asymptomatic

23

Fructose intolerance

AR

Deficiency of aldolase B

Hypoglycemia
Jaundice
Cirrhosis
Vomiting

Tx:
- decrease fructose and sucrose intake

24

Galactokinase deficiency

AR

Deficiency of galactokinase

MIld condition
Infantile cataracts

25

Classic galactosemia

AR

Absence of galactose-1-phosphate uridyltransferase

Present in 1st wk of life

FTT
Jaundice
Hepatomegaly
Infantile cataracts
MR

Tx:
- no galactose and lactose in diet

26

Ornithine transcarbamoylase deficiency

X linked recessive

#1 urea cycle disorder

Can't eliminate ammonia

Increased orotic acid in blood and urine

Dec BUN

Sx of hyperammonemia (tremor, somnolence, vomiting)

Tx:
- supplement with citrulline
- protein restrict

27

Homocystinuria

AR

Can't convert Homocysteine --> Cystathione

3 forms:
- cystathione synthase deficiency
- dec affinity of cystathione syntahse for B6
- Homocysteine methyltransferase deficiency

Cysteine becomes essential!!

- NOrmal at birth
- Increased homocysteine in urine
- MR
- strokes***
- Marfanoid habitus
- downward dislocation of lens

Tx:
- give high doses of B6
- restric methionine
- supplement cysteine

28

Cystinuria

AR

Defect of renal tubular AA for cysteine, ornithine, lysine, arginine in PCT

Tx:
- good hydration
- urinary alkalinization

29

Maple syrup urine disease

AR

Blocked degradation of branched amino acids (Ile, Leu, Val)

- CNS defects
- MR
- Death

30

Hartnup disease

AR

Defective neutral aa transporter on renal and intestinal epithelial cells

Tryptophan excretion in urine and dec absorption in gut

Leads to pellagra!!!

31

Von Gierke's disease

AR

Glycogen storage disease

Findings:
- severe fasting hypoglycemia
- inc glycogen in liver --> hepatomegaly
- inc blood lactate
- hyperURICemia
- hyperLIPIDemia
- nl LFTs
- fat cheeks
- thin extremities
- short stature
- protuberant abdomen
- nl spleen and heart

Deficiency:
- Glucose-6-phosphatase

32

Pompe's disease

AR
= Acid maltase deficiency

Findings:
- Cardiomegaly
- early death
- hepatomegaly
- floppy baby w/ feeding difficulties
- macroglossia

Deficiency:
- lysosomal a-1,4 glucosidase

33

Cori's disease

AR

Findings:
- friends with Von Gierke but not as bad!
- increased LFTs
- normal blood lactate + uric acid
- splenomegaly
- nl kidneys

Deficiency:
- debranching enzyme

Gluconeogenesis ok

34

McArdle's disease

AR

Findings:
- increased glycogen in muscle but can't break down
- painful muscle cramps
- myoglobinuria w/ exercise lots

Deficiency:
- muscle glycogen phosphorylase

35

Marfan features
MR
Thromboembolic events
Downward dislocation of lens

Homocystinuria