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55 Cards in this Set
- Front
- Back
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Peripheral neuropathy of hands/feet, Angiokeratomas, Cardiovascular/Renal Disease
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[Fabry's]
XLR: alpha-galactosidase A deficiency ↑ Ceramide trihexoside |
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HEPATOSPLENOMEGALY, Aseptic necrosis of femur, Bone crises
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[Gaucher's]
Glucocerebrosidase deficiency ↑ Glucocerebroside, MACROPHAGES that look like CRUMPLED TISSUE PAPER ↑ incidence in ASHKENAZI JEWS |
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Progressive neurodegeneration, Cherry-red spot on macula,
HEPATOSPLENOMEGALY |
[Niemann-Pick]
Sphingomyelinase deficiency ↑ Sphingomyelin, FOAM CELLS ↑ incidence in ASHKENAZI JEWS |
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Progressive neurodegeneration, Developmental delay, Cherry-red spot on macula,
NO HEPATOSPLENOMEGALY |
[Tay-Sachs]
Hexosaminidase A deficiency ↑ GM2 ganglioside, LYSOSOMES W/ ONION SKIN ↑ incidence in ASHKENAZI JEWS |
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Peripheral neuropathy, Developmental delay, Optic atrophy
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[Krabbe's]
Galactocerebrosidase deficiency ↑ Galactocerebroside --> destroys myelin sheath, GLOBOID CELLS |
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Central & peripheral demyelination, Ataxia, Dementia
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[Metachromatic Leukodystrophy]
Arylsulfatase A deficiency ↑ Cerebroside sulfate --> impaired production of myelin sheath |
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Developmental delay, Gargoylism, Airway obstruction
CORNEAL CLOUDING HEPATOSPLENOMEGALY |
[Hurler's]
alpha-L-iduronidase deficiency ↑ Heparan sulfate, Dermatan sulfate |
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Mild Developmental delay, Gargoylism, Airway obstruction
HEPATOSPLENOMEGALY +AGGRESSIVE BEHAVIOR NO CORNEAL CLOUDING |
[Hunter's]
XLR: Iduronate sulfatase deficiency ↑ Heparan sulfate, Dermatan sulfate |
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↑ incidence in ASHKENAZI JEWS
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Tay-Sachs (Hexosaminidase A deficiency) = NO HEPATOSPLENOMEGALY
Niemann-Pick (Sphingomyelinase deficiency) = HEPATOSPLENOMEGALY Gaucher's (Glucocerebrosidase deficiency) = HEPATOSPLENOMEGALY |
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[Lysosomal storage diseases - Characteristic cells]:
Macrophages that look like crumpled tissue paper Foam cells Lysosomes w/ onion skin Globoid cells |
[Lysosomal storage diseases - Characteristic cells]:
Gaucher's (↑ Glucocerebroside) Niemann-Pick (↑ Sphingomyelin) Tay-Sachs (↑ GM2 ganglioside) Krabbe (↑ Galactocerebroside) |
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↑ heparan sulfate & dermatan sulfate
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Hurler's (AR: alpha-L-iduronidase deficiency)
or Hunter's (XLR: Iduronate sulfatase deficiency) |
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severe fasting hypoglycemia
↑ glycogen in liver ↑ blood lactate hepatomegaly |
Glucose-6-phosphatase deficiency
(von Gierke's I) |
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cardiomegaly
systemic findings (heart, liver, muscle) leading to early death |
Lysosomal alpha-1,4-glucosidase deficiency
Acid maltase deficiency (Pompe's II) |
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milder:
fasting hypoglycemia ↑ glycogen in liver hepatomegaly but NORMAL BLOOD LACTATE |
Debranching enzyme deficiency
alpha-1,6-glucosidase deficiency (Cori's III) GLUCONEOGENESIS INTACT. |
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↑ glycogen in muscle, but cannot break it down
painful muscle cramps, myoglobinuria w/ strenuous exercise |
Skeletal muscle Glycogen phosphorylase deficiency
(McArdle's V) |
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alpha-galactosidase A deficiency
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↑ ceramide trihexoside
Fabry's (XLR) peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease |
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glucocerebrosidase deficiency
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↑ glucocerebroside
Gaucher's (AR, Ashkenazi Jews) HEPATOSPLENOMEGALY, aseptic necrosis of femur, bone crises, [macrophages that look like crumpled tissue paper] |
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sphingomyelinase deficiency
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↑ sphingomyelin
Niemann Pick (AR, Ashkenazi Jews) HEPATOSPLENOMEGALY, progressive neurodegeneration, cherry-red spot on macula, [foam cells] |
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hexosaminidase deficiency
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↑ GM2 ganglioside
Tay-Sach's (AR, Ashkenazi Jews) NO HEPATOSPLENOMEGALY, progressive neurodegeneration, developmental delay, cherry-red spot on macula, [lysosomes with onion skin] |
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galactocerebrosidase deficiency
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↑ galactocerebroside
Krabbe's (AR) peripheral neuropathy, developmental delay, optic atrophy, [globoid cells] |
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arylsulfatase A deficiency
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↑ cerebroside sulfate (sulfatides)
Metachromatic Leukodystrophy (AR) central & peripheral demyelination with ataxia, dementia |
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alpha-L-iduronidase deficiency
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↑ heparan & dermatan sulfate
Hurler's (CORNEAL CLOUDING, AR) |
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iduronate sulfatase deficiency
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↑ heparan & dermatan sulfate
Hunter's (NO CORNEAL CLOUDING + AGGRESSIVE BEHAVIOR, XLR) |
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glucose-6-phosphatase deficiency
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Von Gierke's (AR)
severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood lactate, HEPATOmegaly |
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lysosomal alpha-1,4-glucosidase deficiency
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Pompe's (AR)
cardiomegaly & systemic (heart, liver, muscle) findings leading to early death |
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acid maltase deficiency
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Pompe's (AR)
cardiomegaly & systemic (heart, liver/hepatomegaly, muscle/hypotonia) findings leading to early death |
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debranching enzyme deficiency
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Cori's (AR)
milder: fasting hypoglycemia, ↑ glycogen in liver, HEPATOmegaly, growth retardation accumulation of small-chain dextrin in hepatocyte cytosol NORMAL BLOOD LACTATE LEVELS. GLUCONEOGENESIS INTACT. |
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alpha-1,6-glucosidase deficiency
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Cori's (AR)
milder: fasting hypoglycemia, ↑ glycogen in liver, HEPATOmegaly, growth retardation accumulation of small-chain dextrin in hepatocyte cytosol NORMAL BLOOD LACTATE LEVELS. GLUCONEOGENESIS INTACT. |
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glycogen phosphorylase deficiency
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McArdle's (AR)
↑ glycogen in muscle, but cannot break it down, leading to painful muscle cramp & myoglobinuria with strenuous exercise |
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Fructokinase deficiency
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Essential Fructosuria
↑ Fructose (but Fructose is not trapped in liver cells) Benign, asymptomatic, fructosuria |
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Aldolase B deficiency
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Fructose Intolerance
↑ Fructose-1-P Hypoglycemia, jaundice, cirrhosis, vomiting Tx: decrease intake of both Fructose & Sucrose (Glucose+Fructose) (phosphorylation prevents fructose from leaving liver cell; also Fructose normally bypasses the rate-limiting step of Glycolysis PFK thru Aldolase B) |
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Galactokinase deficiency
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Galactose shunts to Aldose Reductase --> ↑ Galactitol
Galactosemia, Galactosuria, Infantile cataracts (failure to develop social smile) |
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Galactose-1-phosphate Uridyltransferase deficiency
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Classic Galactosemia
↑ Galactose-1-P in liver cell ↑ Galactitol in lens Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation Tx: exclude intake of Galactose & Lactose (Glucose+Galactose) |
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Sorbitol dehydrogenase (insufficiency in some cells)
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= Schwann cells, Retina, Kidneys (have only Aldose Reductase)
In diabetes, Sorbitol accumulates --> cataracts (lens), retinopathy (retina), peripheral neuropathy (schwann cells) |
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Lactase deficiency
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Brush border enzyme deficiency
Bloating, cramps, diarrhea (may follow gastroenteritis) age-dependent lactose-intolerance in AA's & Asians |
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causes of Hyperammonemia (↑ NH4+)
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Acquired (Hepatic encephalopathy due to liver disease)
or Hereditary (UREA CYCLE ENZYME DEFICIENCIES) excess NH4+ --> depletes alpha-ketoglutarate --> inhibition of TCA cycle |
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Tx for Hyperammonemia
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Limit protein in diet
Benzoate/Phenylbutyrate (bind aa & lead to excretion) may be given to decrease ammonia levels Lactulose to acidify GI tract & trap NH4+ for excretion |
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Ornithine Transcarbamoylase deficiency
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X-LINKED RECESSIVE
↓ BUN, Hyperammonemia ↑ Orotic acid in blood & urine OTC def=interferes w/ body's ability to eliminate ammonia + Excess Carbamoyl Phosphate is converted to Orotic Acid --> Pyrimidine synthesis |
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UMP synthase deficiency
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Orotic Aciduria (AR)
↑ Orotic acid in urine Megaloblastic anemia (does not improve with B12, B9) Failure to thrive Inability to convert Orotic Acid --> UMP Tx: Oral Uridine |
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Phenylalanine hydroxylase deficiency
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Phenylketonuria
↑ Phenylalanine --> excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate) in urine Normal 2-3 days after birth, Mental retardation, Growth retardation, Seizures, Fair skin, Eczema, Musty body odor. |
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Tetrahydrobiopterin cofactor deficiency
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Phenylketonuria
↑ Phenylalanine --> excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate) in urine Normal 2-3 days after birth, Mental retardation, Growth retardation, Seizures, Fair skin, Eczema, Musty body odor. |
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Tx for PKU
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↓ Phenylalanine (in aspartame e.g. NutraSweet) in diet.
↑ Tyrosine in diet (TYROSINE BECOMES ESSENTIAL). |
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lack of proper dietary therapy in PKU mother
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infant with:
Microcephaly, Mental retardation, Growth retardation, Congenital heart defects. |
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Homogentisic Acid Oxidase deficiency
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Alkaptonuria/Ochronosis
↑ Homogentisic acid = toxic to cartilage (dark connective tissue, brown sclera, urine black upon air, debilitating arthralgias) impaired degradation of: Tyrosine --> Fumarate |
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Tyrosinase deficiency
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Albinism (variable inheritance due to locus heterogeneity)
causes: - Tyrosinase deficiency (cannot synth: Tyrosine --> Melanin) - defective Tyrosine transporters - lack of neural crest cell migration |
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Cystathione synthase deficiency
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AR: Homocystinuria, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down & in), ATHEROSCLEROSIS --> stroke & MI
Tx: ↓ Methionine, CYSTEINE BECOMES ESSENTIAL, ↑ B12 & B9 in diet |
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decreased affinity for Cystathione synthase for Pyridoxal phosphate (B6)
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AR: Homocystinuria, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down & in), ATHEROSCLEROSIS --> stroke & MI
Tx: heavily ↑ B6 in diet, CYSTEINE BECOMES ESSENTIAL. |
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Homocysteine methyltransferase deficiency
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AR: Homocystinuria, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down & in), ATHEROSCLEROSIS --> stroke & MI
Tx: requires B12 CYSTEINE BECOMES ESSENTIAL. |
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hereditary defect in: PCT Renal tubular aa transporter for:
Cysteine, Ornithine, Lysine, Arginine |
Cystinuria
hexagonal crystal precipitation & Staghorn calculi Tx: good hydration & urinary alkalinization |
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Carnitine deficiency
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Weakness, hypotonia, hypoketotic hypoglycemia
Inability to transport LCFA's (e.g. Acyl-CoA) into mitochondria --> toxic accumulation of LCFA's in cytoplasm & indirect ↓ ATP production & ↓ gluconeogenesis |
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Acyl-CoA dehydrogenase deficiency
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↑ dicarboxylic acids
& ↓ glucose & ketones |
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AR: LPL deficiency / Altered Apolipoprotein C-II
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Hyper Chylomicronemia
↑ Chylomicrons, TG, Cholesterol Pancreatitis Hepatosplenomegaly Eruptive/Pruritic xanthomas no ↑ risk for atherosclerosis =) |
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AD: Absent/Decreased LDL receptors
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Familial Hypercholesterolemia
↑LDL, Cholesterol Accelerated atherosclerosis Tendon (Achilles) xanthomas Corneal arcus |
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AD: Hepatic overproduction of VLDL
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Hypertrygleridemia
↑VLDL, TG Acute pancreatitis |
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B-48 & B-100 deficiency
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Abetalipoproteinemia
AR: MTP (microsomal triglyceride transfer protein) gene mutation → Decreased B-48 & B-100 ↓ Chylomicron & VLDL synthesis & secretion 1st few months of life: failure to thrive, steatorrhea, acanthocytes in bloodstream, ataxia, night blindness intestinal biopsy: enterocytes w/ lipid accumulation (due to inability to export absorbed lipid as chylomicrons) |
