Glycogen storage, Lysosomal storage, Metabolism diseases Flashcards
Lesch Nyhan
HGPRT Deficiency (XR) *Excess uric acid production leading to gout *intellectual disability *self mutilation *aggression *dystonia TX: Allopurinol and Febuxostat
I-Cell DZ
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
Lysosomal Storage Diseases
I Cell DZ Fabry Gauchier Niemann-Pick Tay Sachs Krabbe Metachromatic leukodistrophy Hurler syndrome Hunter Syndrome
Niemann-Pick disease
Sphyngomyelinase deficiency (AR) leads to accumulation of SPHINGOMYELIN *Seen in CNS and cerebellum *HEPATOSPLENOMEGALY *Progressive neurodegeneration *cherry red spot on fundoscopic examiniation *“Foam cells”
Tay-Sachs disease
Hexosaminidase A D (AR) Buildup of GM2 GANGLIOSIDE *Cherry red spot on macula, ONION SKINNING of lysosomes *Progressive neurodegeneration DEATH BY AGE 4
Fabry Dz
ALPHA GALACTOSIDASE A D (XR) Buildup of CERAMIDE TRIHEXOSIDE *Peripheral neuropathy *ANgiokeratomas *CV/Renal DZ with mesenteric ischemia
Gaucher DZ
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
Krabbe Leukodystrophy
Galactocerebrosidase D (AR) leads to ^ GALACTOCEREBROSIDE psychosine *peripheral neuropathy *Developmental delay *optic atrophy *globoid cells FATAL BEFORE AGE 2
Metachroomatic Leukodystrophy
ARYLSULFITASE A D (AR) leads to ^ CEREBROSIDE sulfate *Central and peripheral demyelination *Ataxia *Dementia METACHROMATIC staining
Hurler Syndrome
alpha-L-IRONIDASE D (AR) causes ^ HEPARAN & DERMATAN sulfate *Gargoylism *Devo delay *airway obstruction *corneal clouding *hepatosplenomegaly
Hunter Syndrome
IDURONATE SULFATASE D (XR) ^ HEPARIN & DERMATAN SULFATE *Mild Hurler + Aggressive behavior *No corneal clouding
Pyruvate Dehydrogenase Deficiency
^ Pyruvate *Lactic acidosis (2/2 LDH) *Neuro defects *Increased alanine (2/2 ALT) TX: KETOGENIC FOODS (fats) and AA(Lysine Leucine)
G6P D
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
Essential Fructosuria
Fructokinase D (AR) Benign fructose in urine
Fructose intolerance
Aldolase B D (AR) ^ F1P and v Available phosphate *Hypoglycemia *Jaundice/Cirrhosis *Vomiting TX: Eliminate fructose and Sucrose from diet
Galactokinase D
AR Galctose in blood and urine (maybe galactitol) *Infantile cateracts lack of tacking/ social smile
Classic Galactosemia
Galac1P Uridyltransferase D (AR) causes ^GALACTITOL *Infantile Cataracts *Failure to thrive *jaundice *hepatomegaly *intellectual Disability TX: Exclude galactose and Lactose from diet
Ornithine Transcarbamylase D
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
N-Acetylglutamate deficiency
Needed for CPS 1 –> hyperammonemia ^ornathine without orotic aciduria Normal urea cycle enzymes/ No enzyme deficiency
PKU
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.
Maple Syrup Urine Disease
Alpha Keto-acid Dehydrogenase D (AR) B1 dependent I Love Vermont- Isoleucine, Leucine, Valine *CNS Defects *Intellectual diability *death TX: Restrict ILV, Thiamine supplement
Alkaptonuria
HOMOGENSADE OXIDASE D (AR) *Cant degrade tyrosine *Benign darkening of connective tissue *Dark urine on standing DEBILITATING Arthritis
Homocysteinuria
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
Cystinuria
COLA transporter D (AR) *Hexagonal renal cysteine stones *2 Cysteine covalently bonded TX: Alkalinize urine (acetazolamide), and Chelating agents
Hartnup Dz
Cant uptake neutral AA Tryptophan/ Niacin Deficiency *Pellagra: Dermatitis, diarrhea, dimentia TX: Niacin supplements
McArdle DZ
MYOPHOSPHORYLASE (skeletal M glycogen phosphorylase) D AR *^ Muscle glycogen, painful muscle cramps and osmotic lysis of muscle cells with exercise. *rare arrhythmias
Von Gierke DZ
G6Pase D (AR) *Severe fasting hypoglycemia *^ Glycogen in liver/ HEPATOMEGALY *^ Blood lactate TX: Oral cornstarch and frequent feeding. Avoid galactose and fructose
Cori DZ
Debranching Enzyme D (AR) *Branched Glycogen in liver *Mild hepatomegaly and low fasting glucose
Pompe DZ
Lysosmal alpha 1-4 Glucosidease D (AR) *endsosomal glycogen deposits *CARDIOMYOPATHY –>Death (heart) *SYSTEMIC DISEASE –>Death (liver muscle)
Carnetine D
Unable to transport LCFA into mito for Oxidation *Weakness/hypotonia *Hypoketotic hypoglycemia
Acyl- CoA Dehydrogenase D
*decreased FA B- Oxidation *v Gluconeogeneis (Acetyl CoA is activator) * Decreased fasting glucose
Adenosine Deaminase deficiency
(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
Lead poisoning
Inhibits Ferochelase and ALA dehydratase 6 ALA/ Protopophyrin *Macrocytic anemia, Kidney dz BASOPHILIC STIPPLING
Acute Intermittent Pophyria
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
Porphyria Cutanea Tarda
UROPOPHRYHOGEN DECARBOXYLASE D - ^ Uroporphyrin *BLISTERING PHOTOSENSITIVITY *Liver involvement *Tea colored urine *hypertrichosis *facial pigmentation *HepC, Alcoholism, LFTs
Lesch Nyhan
HGPRT Deficiency (XR) *Excess uric acid production leading to gout *intellectual disability *self mutilation *aggression *dystonia TX: Allopurinol and Febuxostat
