Metabolic diseases Flashcards
What is albinism?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 268
Lack of melanin (tyrosine derivative) resulting in lack of pigmentation
Enzyme: tyrosinase
Clincial presentation: abnormal pigmentaiton of skin, hair, and eyes
What is CPS I deficiency?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 270
Impaired clearance of nitrogen via urea cycle
Enzyme: Carbamoyl phosphate synthetase I (ammonium + bicarbonate ► carbamoyl phosphate) (mitochondrial protein)
Clinical manifestation: hyperammonemia, poor respirtory and temprature regualtion, lethargy, seizures, developmental delay, MR
What is cystic fibrosis?
What protein is responsible?
What are the main clinical manifestations?
Panini pg. 95
Thickened mucous (primarily in airways) due to inefficecnt pumping of Cl- out of epithelium
Protein: CFTR (cystic fibrosis transmembrane conductance regulator) (primary active Cl- transporter)
Clinical manifestation: difficulty breathing
What is cystinuria?
What protein is responsible?
What are the main clinical manifestations?
Panini pg. 93
Accumulation of dimeric cystine resulting in deposits in kidneys
Protein: dimeric cystine transporter
Clinical manifestation: renal colic
What is Fanconi-Bickel syndrome?
What protein is responsible?
What are the main clinical manifestations?
Panini pg. 117
Inability of glucose, galactose, and fructose to cross cell membrane of certain cell types (liver, pancreatic β cell, and proximal renal tubule).
Protein: GLUT 2 (glucose, galactose, and fructose transporter)
Clinical manifestation: hepatomegly, tubular nephropathy, decreased insulin secretion (failure of β cells to detect glucose)
What is classical galactosemia?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 189-190
Accumulation of galactitol to to inability to convert galactose to glucose
Enyzme: GALT (galactose 1-P ► glucose 1-P)
Clinical manifestation: liver failure, failure to thrive, sepsis, cataracts
What is nonclassical galactosemia?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 189-190
Accumulation of galactitol to to inability to convert galactose to glucose
Enzyme: galactokinase (galactose ► galactose 1-P)
Clinical manifestation: cataracts
What is GSD 0?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Name: GSD 0
Enzyme: Glycogen synthase
Glycogen: unable to synthesize
Symptoms: fasting hypoglycemia, muscle cramping
What is GSD I?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 177-178;180
Name: Von Gierke
Enzyme: Glucose 6-phosphatase
Glycogen: Increased amount, unable to release glucose from the liver, normal structure
Symptoms: fasting hypoglycemia, lactic acidosis, hepatomegaly
What is GSD II?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 178;180;184
Name: Pompe
Enzyme: Acid maltase (lysosomal)
Glycogen: Massive increased amount, normal structure
Symptoms: muscle weakness (skeletal and cardiac)
What is GSD III?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 178;180;185
Name: Cori
Enzyme: α-1,6-glucosidase (debranching enzyme)
Glycogen: large number of short branches, increased amount
Symptoms: hepatomegaly
What is GSD IV?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 178;180
Name: Andersen
Enzyme: glucosyl (4:6) transferase (branching enzyme)
Glycogen: long chains with few branches, normal amount
Symptoms: hepatospelnomegaly, cirrhosis
What is GSD V?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 178;180;185
Name: McArdle
Enzyme: muscle glycogen phosphorylase
Glycogen: increased amount, normal structure
Symptoms: weakness, fatigue, cramping, excercise intolerance
What is GSD VI?
What enzyme is responsible for the deficiency?
What is the nature of glycogen with the disorder?
What are the symptoms?
Panini pg. 178;180;184
Name: Hers
Enzyme: liver glycogen phosphorylase
Glycogen: increased amount, normal structure
Symptoms: hepatomegly, hypoglycemia
What is gout?
What enzyme is responsible?
What are the main clinical manifestations?
What medication is used to treat gout?
Panini pg. 278
Excessive production of uric acid leading to painful deposits
Enzyme: Xanthine oxidase (hypoxanthine (AMP) ► xanthine (A/GMP) ► uric acid)
Clinical manifestation: gouty arthritis (primarily in feet), kidney damage
Treatment: Allopurinol
What is Hartnup disease?
What protein is responsible?
What are the main clinical manifestations?
Panini pg. 93;255
Inadequate tryptophan (precursor for vitamin B3/naicin)
Protein: nonpolar AA transporter
Clinical manifestation: photosenstivie dermatitis, failure to thrive, ataxia, nystagmus
Also known as Pellagra-like dermatitis
What is lactose intolerance?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 190
Inability to metabolize intestinal lactose which results in increased osmotic load in lumen.
Enzyme: Lactase (lactose ► galactose)
Clincial manifestation: diarrhea and excess flatulence
What is Lesch-Nyhan syndrome?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 284
Excess guanine and hypoxanthine due to defective purine salvage pathway which are degraded to uric acid instead of being used to regnerate GMP and IMP. Also excessive purine synthesis due to overabundance of PRPP.
Enzyme: HGPRT (hypoxanthine-guanine phosphoribosyltransferase) (guanine/hypoxanthine ► GMP/IMP)
Clinical presentation: self-mutilation, MR, neuromuscular dysfunction, gout-like symptoms
What is maple syrup urine disease (MSUD)?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 267
Inability to break down branched-chain AAs (valine, leucine, and isoleucine) resulting in build up in urine.
Enzyme: BCKD (branched-chain α-keto acid dehydrogenase complex)
Clinical manifestation: urine that smells like maple syrup, MR
What is MCAD deficiency?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 217
Inability to break down medium-chain fatty acids
Enzyme: medium-chain acyl CoA dehydrogenase (MCFA ► acetyl CoA)
Clinical manifestation: hypoglycemia (sometimes fatally)
What is Neimann-Pick disease?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 90
Accumulation of sphingomyelin in lysosomes of liver, spleen, CNS, and bone marrow.
Enzyme: A-SMase (acid sphingomyelinase) (sphingomyelin ► ceramide + phosphorycholine)
Clinical manifestation: “cherry red spot” in eye, hepatosplenomegaly, MR, ataxia, seizures
What is PDCD?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 129
Inadequate conversion of pyruvate to acetyl CoA. Pyruvate is instead shunted to make lactate.
Enzyme: pyruvate dehydrogenate complex (pyruvate ► acetyl CoA)
Clinical manifestation: lactic acidosis (metabolilc); mircocephaly, lethargy, hypotonia (neurologic)
What is phenylketonuria (PKU)?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 268
Inability to metabolize phenylalanine resulting in accumulation of phenyllactate and phenylacetate. These compounds inhibit AA transport in the brain and inhibit myelin formation.
Enzyme: PAH (phenylalanine hydrozylase) (phenylalanine ► tyrosine)
Clinical manifestation: musty smelling urine; if untreated, microcephaly, learning disorders, seizures
**NOTE**: pathopysiology does not start until after birth as mother metabolizes phenylalanine; if treated adequately, minimal symptoms are possible
What is severe combined immunodeficiency?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 278
Excessive of AMP resulting in inhibition of synthesis of other nucleotides. This affects lymphocytes the most, disrupting T cell and B cell maturation resulting in minimal adaptive immune system function.
Enzyme: adenosine deaminase (ADA) (adenosine ► inosine)
Clinical manifestation: “bubble boys” (inability to tolerate exposure to enviornment due to extreme risk of fatal infection)
X-linked
What is Tarui disease?
What enzyme is responsible?
What are the main clinical manifestations?
Panini pg. 171
Inefficient glycolysis (rate-limiting step is affected)
Enzyme: phosphofructokinase-1 (PFK-1)
Clinical manifestation: excercise induced weakness and cramps, hemolytic anemia, hyperbilirubinemia/jaundice
