Glycogen storage, Lysosomal storage, Metabolism diseases

Question 1

Lesch Nyhan

Answer 1

HGPRT Deficiency (XR) *Excess uric acid production leading to gout *intellectual disability *self mutilation *aggression *dystonia TX: Allopurinol and Febuxostat

Question 2

I-Cell DZ

Answer 2

Problem attaching M6P to lysosomal proteins in golgi (phosphotransferase D) Proteins secreted instead (in secretory granules) *Coarse facial features *Clouded corneas *Restricted joint mvt. *high plasma lysosomal proteins OFTEN FATAL IN CHILDHOOD

Question 3

Lysosomal Storage Diseases

Answer 3

I Cell DZ Fabry Gauchier Niemann-Pick Tay Sachs Krabbe Metachromatic leukodistrophy Hurler syndrome Hunter Syndrome

Question 4

Niemann-Pick disease

Answer 4

Sphyngomyelinase deficiency (AR) leads to accumulation of SPHINGOMYELIN *Seen in CNS and cerebellum *HEPATOSPLENOMEGALY *Progressive neurodegeneration *cherry red spot on fundoscopic examiniation *“Foam cells”

Question 5

Tay-Sachs disease

Answer 5

Hexosaminidase A D (AR) Buildup of GM2 GANGLIOSIDE *Cherry red spot on macula, ONION SKINNING of lysosomes *Progressive neurodegeneration DEATH BY AGE 4

Question 6

Fabry Dz

Answer 6

ALPHA GALACTOSIDASE A D (XR) Buildup of CERAMIDE TRIHEXOSIDE *Peripheral neuropathy *ANgiokeratomas *CV/Renal DZ with mesenteric ischemia

Question 7

Gaucher DZ

Answer 7

MOST COMMON GLUCOCEREBROCIDASE D (XR) leads to ^ GLUCOCEREBROSIDE *hepatosplenomegaly *pancytopenia *Aseptic necrosis of femur *bone crises *Gaucher Cells- LIPID LADEN MACs RESEMBLING CRUMPLED TISSUE PAPER TX:rGLUCOCEREBRSIDASE

Question 8

Krabbe Leukodystrophy

Answer 8

Galactocerebrosidase D (AR) leads to ^ GALACTOCEREBROSIDE psychosine *peripheral neuropathy *Developmental delay *optic atrophy *globoid cells FATAL BEFORE AGE 2

Question 9

Metachroomatic Leukodystrophy

Answer 9

ARYLSULFITASE A D (AR) leads to ^ CEREBROSIDE sulfate *Central and peripheral demyelination *Ataxia *Dementia METACHROMATIC staining

Question 10

Hurler Syndrome

Answer 10

alpha-L-IRONIDASE D (AR) causes ^ HEPARAN & DERMATAN sulfate *Gargoylism *Devo delay *airway obstruction *corneal clouding *hepatosplenomegaly

Question 11

Hunter Syndrome

Answer 11

IDURONATE SULFATASE D (XR) ^ HEPARIN & DERMATAN SULFATE *Mild Hurler + Aggressive behavior *No corneal clouding

Question 12

Pyruvate Dehydrogenase Deficiency

Answer 12

^ Pyruvate *Lactic acidosis (2/2 LDH) *Neuro defects *Increased alanine (2/2 ALT) TX: KETOGENIC FOODS (fats) and AA(Lysine Leucine)

Question 13

G6P D

Answer 13

XR - African americans *Inability to produce NADPH - cant reduce glutathione Hemolysis with oxidative stress (fava beans, sufa, primaquine/chloro, Anti TB drugs) *Heinz bodies and Bite cells

Question 14

Essential Fructosuria

Answer 14

Fructokinase D (AR) Benign fructose in urine

Question 15

Fructose intolerance

Answer 15

Aldolase B D (AR) ^ F1P and v Available phosphate *Hypoglycemia *Jaundice/Cirrhosis *Vomiting TX: Eliminate fructose and Sucrose from diet

Question 16

Galactokinase D

Answer 16

AR Galctose in blood and urine (maybe galactitol) *Infantile cateracts lack of tacking/ social smile

Question 17

Classic Galactosemia

Answer 17

Galac1P Uridyltransferase D (AR) causes ^GALACTITOL *Infantile Cataracts *Failure to thrive *jaundice *hepatomegaly *intellectual Disability TX: Exclude galactose and Lactose from diet

Question 18

Ornithine Transcarbamylase D

Answer 18

XR Defect in ornathine + carbamoyl phosphate –> Citruline Carb Phoaphate converted to OROTIC ACID *^OOROTIC ACID *v BUN *Hyperammonemia and hepatic encephalopathy- (Slurring of speech, somnolence, vomiting, cereberal edema,vision problems) TX: decrease protein, give BENZOATE, BIOTIN, PHENYLBUTYRATE

Question 19

N-Acetylglutamate deficiency

Answer 19

Needed for CPS 1 –> hyperammonemia ^ornathine without orotic aciduria Normal urea cycle enzymes/ No enzyme deficiency

Question 20

PKU

Answer 20

PHENYLALANINE OH-ASE D or BH4 D (AR) ^ Phenylketones in urine- v aromatic acid metabolism *intellectual disability *Mousy/musty smell *Fair skin *Eczema *Growth retardation TX: Avoid aspartame, dairy, meat, fish, chicken, beans, nuts- BH4 sup.

Question 21

Maple Syrup Urine Disease

Answer 21

Alpha Keto-acid Dehydrogenase D (AR) B1 dependent I Love Vermont- Isoleucine, Leucine, Valine *CNS Defects *Intellectual diability *death TX: Restrict ILV, Thiamine supplement

Question 22

Alkaptonuria

Answer 22

HOMOGENSADE OXIDASE D (AR) *Cant degrade tyrosine *Benign darkening of connective tissue *Dark urine on standing DEBILITATING Arthritis

Question 23

Homocysteinuria

Answer 23

CYSTATHIONE SYNTHASE D (cant make cysteine) or HOMOCYSTEINE METHYLTRANSFERASE D (cant make methionine) *^ Homocysteine in urine *intellectual disability *tall with Kyphosis and osteoporosis *Down and in lens subluxation *Atherosclerosis/ Thromboembolism/ Stroke (EVEN IN KIDS) TX: Increase cysteine or methionine, B12/B6 supplementation

Question 24

Cystinuria

Answer 24

COLA transporter D (AR) *Hexagonal renal cysteine stones *2 Cysteine covalently bonded TX: Alkalinize urine (acetazolamide), and Chelating agents

Question 25

Hartnup Dz

Answer 25

Cant uptake neutral AA Tryptophan/ Niacin Deficiency \*Pellagra: Dermatitis, diarrhea, dimentia TX: Niacin supplements

Question 26

McArdle DZ

Answer 26

MYOPHOSPHORYLASE (skeletal M glycogen phosphorylase) D AR \*^ Muscle glycogen, painful muscle cramps and osmotic lysis of muscle cells with exercise. \*rare arrhythmias

Question 27

Von Gierke DZ

Answer 27

G6Pase D (AR) \*Severe fasting hypoglycemia \*^ Glycogen in liver/ HEPATOMEGALY \*^ Blood lactate TX: Oral cornstarch and frequent feeding. Avoid galactose and fructose

Question 28

Cori DZ

Answer 28

Debranching Enzyme D (AR) \*Branched Glycogen in liver \*Mild hepatomegaly and low fasting glucose

Question 29

Pompe DZ

Answer 29

Lysosmal alpha 1-4 Glucosidease D (AR) \*endsosomal glycogen deposits \*CARDIOMYOPATHY --\>Death (heart) \*SYSTEMIC DISEASE --\>Death (liver muscle)

Question 30

Carnetine D

Answer 30

Unable to transport LCFA into mito for Oxidation \*Weakness/hypotonia \*Hypoketotic hypoglycemia

Question 31

Acyl- CoA Dehydrogenase D

Answer 31

\*decreased FA B- Oxidation \*v Gluconeogeneis (Acetyl CoA is activator) \* Decreased fasting glucose

Question 32

Adenosine Deaminase deficiency

Answer 32

(AR) Purine salvage deficiency causing hyper ATP and dATP Negative feedback on purine synthesis Results in a severe combined immunodeficiency -Failure to thrive -Chronic diarrhea -Recurrent infections of all types (Signs: No thymic shadow, v TRECs, no T cells

Question 33

Lead poisoning

Answer 33

Inhibits Ferochelase and ALA dehydratase 6 ALA/ Protopophyrin \*Macrocytic anemia, Kidney dz BASOPHILIC STIPPLING

Question 34

Acute Intermittent Pophyria

Answer 34

Porphobilinogen Deaminase D causes ^ PORPHOBILINOGEN ,ALA, Coporhobilinogen \*Early Heme synthesis \*Painful abdomen, PORT WINE URINE- darkens on standing, Polyneuropathy, psychological \*PRECIPITATED BY DRUGS, ETOH, STARVATION TX: Glucose and HEME --IALA synthase

Question 35

Porphyria Cutanea Tarda

Answer 35

UROPOPHRYHOGEN DECARBOXYLASE D - ^ Uroporphyrin \*BLISTERING PHOTOSENSITIVITY \*Liver involvement \*Tea colored urine \*hypertrichosis \*facial pigmentation \*HepC, Alcoholism, LFTs

Question 36

Lesch Nyhan

Answer 36

HGPRT Deficiency (XR) \*Excess uric acid production leading to gout \*intellectual disability \*self mutilation \*aggression \*dystonia TX: Allopurinol and Febuxostat