Disorders of Chemistry Flashcards
Aminoacidopathies
class of inherited errors of metabolism in which there is an enzyme defect that inhibits the body’s ability to metabolize certain amino acids.
Phenylketonuria (PKU)- classic form
Absence of activity of phenylalanine hydroxyls (PAH) due to mutations in PAH gene; newborn concentrations are >1200 umol/L (can be as high as 2.4 mmol/L); other elevated metabolites include phenylpyruvic acid, phenylpyruvate (phenylketone), and phenyl lactic acid; decrease in tyrosine; detected by blood or urine measurements; urine will smell musty or mousy; infants and children exhibit mental retardation and microcephaly; managed by low phenylalanine diet; positive Guthrie test (qualitative); microfluorometric assay of blood spot; HPLC; or LC-MS (Phe/Tyr ratio determined; >1 is PKU)
Phenylketonuria (PKU)- mild form
partial PKU deficiency; PAH concentration between 600-1200 umol/L; treatment by sapropterin dihyrochloride (Kuvan) increases activity of PAH enzyme and low phenylalanine diet.
non-PKU mild Hyperphenylalanimeia
PAH concentrations between 180-600 umol/L; no accompanying accumulation of phenylketones; may be caused by cofactor deficiency (enzymes for BH4 synthesis and regeneration which will also results in deficiency of neurotransmitters from tyrosine and tryptophan (treatment entails supplements of L-DOPA and 5-OH tryptophan)
Tyrosinemia
Inborn metabolic disorder of tyrosine catabolism is characterized by excretion of tyrosine and its catabolites in urine (tyrosinuria). elevated tyrosine in blood by MS/MS; elevated succinylacetone (toxic); treatment is low protein diet and nitisinone
Tyrosinemia-Type I
most severe form; 1 in 100,000 births worldwide; caused by mutation in the FAH gene, which codes for the enzyme fumarylacetoacetate hydrodrolase (FAH), which is the last of 5 enzymes required for metabolism of tyrosine; symptoms manifest in first few months of life; failure to thrive, diarrhea, vomiting, jaundice, a cabbage-like odor, distended abdomen, swelling of legs, and increased predisposition for bleeding; untreated, patients will not live past 10 years old
Tyrosinemia-Type II
1 in 250,000 births worldwide; caused by mutation in TAT gene, which leads to a deficiency of the enzyme tyrosine aminotransferase (TAT), first of the 5 enzymes involved in tyrosine metabolism; half of patients will exhibit impaired mental development; other symptoms include photo sensitivity (photophobia), eye pain and redness, and painful skin lesions on palms and soles of feet
Tyrosinemia-Type III
few cases worldwide (very rare); mutation in HPD gene that results in deficiency of the enzyme 4-hyroxyphenylpyruvate deoxygenate (HPD); second of 5 enzymes involved in tyrosine metabolism; impaired mental development, seizures, and some intermittent loss of balance and coordination;
Alkaptonuria
inherited autosomal recessive disorder; 1 in 250,000 births worldwide; caused by mutation HGD gene; leads to deficiency of the enzyme homogentisate oxidase; elevated levels of homogentisic acid in blood, connective tissues, and urine; symptoms appear in 3rd decade of live (30s); dark-blue/black pigmentation (ochronosis); urine will turn brown/black in color when exposed to air; treatment with Vitamin C;
azotemia
elevated urea in blood
uremia
very high plasma urea concentrations accompanied by renal failure
Prerenal azotemia
result of reduced renal blood flow; less blood is delivered to kidney; consequently, less urea is filtered. elevates plasma urea but plasma creatinine remains normal = high urea N/creatinine ratio
Causative factors of prerenal azotemia
congestive heart failure, shock, hemorrhage, dehydration, and other factors that result in a significant decrease in blood volume; high protein diet and increased protein catabolism (caused by stress, fever, major illness, corticosteroid therapy, and GI hemorrhage)
renal azotemia
result of decreased renal function due to compromised urea excretion;
Causative factors of renal azotemia
acute and chronic renal failure, glomerular nephritis, tubular necrosis,
post renal azotemia
result of obstruction of urine flow at any point in the urinary tract; high urea N/creatinine ratio with elevated creatinine
Causative factors of postrenal azotemia
renal calculi, tumors of the bladder or prostate, or severe infection
decreased urea plasma
low protein intake and severe liver disease; late stage pregnancy and in infancy due to increased protein synthesis; low urea N/creatinine ratio
Glomerular nephritis
type of kidney disease where there is inflammation of the glomeruli (tiny filters that remove excess waste and fluids from the blood); detected by urinalysis (red or white blood cells, infection, or high protein content),
Glomerular nephritis causes
toxins, medicines, viral infections (i.e. hep b or c, HIV), IgA nephropathy, lupus-related kidney inflammation, bacterial infections (strep/staph)
Hyperuricemia
result of overproduction of uric acid, increased metabolism of of cell nuclei; can be exacerbated by a purine rich diet, drugs (chemotherapy), and alcohol;
Lesch-Nyhan
X-linked genetic disorder (males) caused by complete deficiency of hypo-xanthine-guanine phosphoribosyltransferase, an important enzyme in the biosynthesis of purines; results in high plasma and urine concentrations of uric acid
Hyperargininemia
High blood ammonia; normal anion gap; increased arginine and increased orotic acid
Citrullemia
High blood ammonia; normal anion gap; increased citrulline (significant); decreased arginine
Ornithine transcarbamylase deficiency (OTC)
High blood ammonia; normal anion gap; decreased arginine; decreased citrulline, increased glutamine; normal orotic acid
Carbamoylphosphataste synthase I (CPSI) deficiency
High blood ammonia; normal anion gap; decreased citrulline, increased glutamine
Argininosuccinic acidemia (acidula) (ASA)
High blood ammonia; normal anion gap; increased citrulline; decreased arginine; increased argininosuccinic acid in urine
Urea Cycle Disorder
High blood ammonia; normal anion gap
Pyruvate decarboxylase (PC) deficiency
Increased ammonia; high anion gap; with ketosis; increased ammonia; increased lactate; increased pyruvate; increased acetoacetate
Organic Acidemia
Increased ammonia; high anion gap; with ketosis; increased ammonia; normal lactate
Hypoglycemia
decreased glucose
Fatty acid oxidation (FAO) defect
normal plasma ammonia; increased anion gap; no ketosis; increased lactate; hypoglycemia
3-hydroxy-3-methylglutaryl-Co (HMG-CoA) lyase deficiency
normal plasma ammonia; increased anion gap; no ketosis; increased lactate; hypoglycemia; increased leucine; Elevated C5-OH (acylcarnitine)
Normoglycemia
normal glucose
Pyruvate dehydrogenase (PDH) deficiency
normal plasma ammonia; increased anion gap (severe acidosis); no ketosis; increased lactate; normoglycemia; increased alanine in urine
Renal tubular acidosis
normal plasma ammonia; increased anion gap; no ketosis; normal lactate; decreased K+
galactosemia
normal plasma ammonia; normal anion gap; increased galactose; decreased GALT activity
Fructose-1,6-biphosphatase (FBP) deficiency
normal plasma ammonia; high anion gap; with ketosis; increased lactate; hypoglycemia
Glycogen Storage Disease (GSD I -Von Gierke)
normal plasma ammonia; high anion gap; with ketosis; increased lactate; hypoglycemia; enlarged liver
Respiratory Chain Disorder
normal plasma ammonia; high anion gap; with ketosis; increased lactate; hypo or normoglycemia
Adrenal Insufficiency
normal plasma ammonia; high anion gap; with ketosis; normal lactate; hypoglycemia
Maple Syrup Urine Disease (MSUD)
normal plasma ammonia; high anion gap; with ketosis; normal lactate; normoglycemia; maple syrup odor in urine; elevated BCAA (including all-isoleucine); elevated BCKA; elevated leucine/isoleucine; increased 2-OH-isovaleric acid
3-met-crotonyl-CoA carboxylase deficiency
normal glucose, normal ammonia
THAN
increased ammonia in premature newborn <24 hrs of age;
B-6 dependency
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
B-6 dependency
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
Biotinidase deficiency
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
NCL
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
GM2
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
CRSM Syndrome
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
Leigh Disease
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
Alpers Disorder
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
MELAS
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)
inability to breakdown long-chain fatty acids; hypoglycemia; photophobia; elevation of C16-OH and other hydroxyacylcarnitine species
Medium-chain acyl-CoA dehydrogenase (MCAD)
inability to breakdown medium-chain fatty acids; nonketotic hypoglycemia; seizures; Elevations of C8, C6, C10, C10:1 acylcarnitines; Elevations of urinary dicarboxylic acids, hexanoylglycine, suberylglycine, and cis-4-decenoic acid; Classis- Have hepatomegaly accompanied by hypoketotic hypoglycemia, hyperuricemia, elevated LFTs, mild hyperammonemia, elevated anion gap
Very long-chain acyl-CoA dehydrogenase (VLCAD)
inability to breakdown very long-chain fatty acids; hypoglycemia; seizures; elevated C14:1 +/- other long-chain acylcarnitines
B-6 dependency
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of great matter disease - seizures, visual impairment; dementia; decreased B-6; metabolic disorders prevented or alleviated by B-6 (pyridoxine)
Biotinidase deficiency
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia; decreased biotinidase activity; hypotonia
Neuronal ceroid lipofuscinosis (NCL)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia
GM2
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia; lysosomal storage disorders; Reduced plasma α-galactosidase enzyme activity
Cherry red spot myoclonus syndrome (CRSM) Syndrome (Sialidosis; Mucolipidosis)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia; abnormal oligosaccharide pattern in urine; deficiency of alpha-N -acetyl neuraminidase activity
Leigh Disease
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia; lactic acidosis; hyperalaninemia; increase of lactate/pyruvate ration in blood; elevation of 2-oxyglutarate, succinate, fumarate and malate; Ethylmalonic encephalopathy
Gaucher
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); HSM and bone
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of grey matter disease - seizures, visual impairment; dementia
Canavan Disease
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of white matter disease - motor difficulties, disorders of tone; increased N-acetyl-L-aspartate (NAA
Alexander Disease
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of white matter disease - motor difficulties, disorders of tone
X-Linked Adrenoleukodystrophy (XLALD)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of white matter disease - motor difficulties, disorders of tone; VLCAD
Metachromatic leukodystrophy (MLD)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of white matter disease - motor difficulties, disorders of tone; decreased sulfatase enzyme activity; urinary sulfatide excretion
Krabbe globoid-cell leukodystrophy (GLD)
Chronic encephalopathy; not abnormal outside CNS (only neural); signs of white matter disease - motor difficulties, disorders of tone; decrease in GALC enzyme activity
Gaucher
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); HSM and bone; decreased beta-glucosidase leukocyte activity
Norrie Disorder (NDP)
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); HSM and bone
Mucopolysaccharidosis (MPS)
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); HSM and bone; increase in urine glycosaminoglycans; deficiency of α-L-iduronidase
Zellweger
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); HSM and bone; VLCD; abnormal C27-bile acid; abnormal dicarboxylic acids and pipecolic acid in plasma
Homocystinuria
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); Skin with tissue; elevated methionine; markedly elevated total plasma homocysteine
Menkes
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); Skin with tissue; hyperbilirubinemia; decreased ceruloplasmin;
Fucosidoses
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); Skin with tissue; deficiency of the enzyme alpha-L-fucosidase
Galactosialidosis
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); Skin with tissue; impaired functioning of cathepsin A
Prolidase Deficiency
Chronic encephalopathy; abnormal outside CNS (neurological visceral and muscular skeletal); Skin with tissue
Multiple sclerosis
oligoclonal banding of CSF proteins not present in serum; elevated IgG in CSF; elevated IgG index; significantly increased white blood cell count CSF; impaired transmission along optic nerve;
myocardial infarction
elevated CK-MB greater than 6% of the total CK (rises within 4-8 hours, peaks at 12-24 hours, returns to normal in 48-72 hours; not specific to AMI); increased levels of troponin I and T
Muscular dystrophy
Elevated levels of serum aldolase; elevated CK values; genetic test is definitive
polymyositis
Elevated levels of serum aldolase; increase in CK levels; increase in myositis antibodies
hypothyroidism
low level of thyroxine and high level of TSH
malignant hyperthermia
increased CK levels, molecular test definitive
ischemia
implication of myocardial infarction
Duchenne type muscular dystrophy
elevated CK levels, molecular test definitive
Reye’s syndrome
increased serum ammonia; increased serum transaminase; encephalopathy
Rocky Mountain spotted fever
indirect immunofluorescence antibody (IFA) assay for immunoglobulin G (IgG) using R. rickettsii antigen; Thrombocytopenia, slightly increased hepatic transaminase levels, normal or slightly increased white blood cell count with increased immature neutrophils, hyponatremia
Carbon monoxide poisoning
elevated level of carboxyhemoglobin;
hemolytic anemia
decreased haptoglobin; elevated LDH; increased unconjugated bilirubin; increased reticulocyte count; urobilinogen, positive for blood
megaloblastic anemia
decrease in HGB, hemcrit, WBCs, RBCs, platelets; increased serum total and indirect bilirubin; increased serum LDH;
- B12 deficiency (decreased B12; increased serum methylmalonic acid; increased serum homocysteine);
- folate deficiency (decreased serum folate; decreased RBC folate; increased serum homocysteine;
pulmonary pneumonia
Leukocytosis; elevations in creatinine and blood urea nitrogen; low blood oxygen levels;
lymphocytosis
increase of white blood cells due to infection
pancreatitis
serum amylase and/or lipase significantly elevated; significant elevation of triglycerides; increased BUN
pernicious anemia
highest total LDH levels
Paget’s disease
osteitis deformans; highest elevation of ALP; elevations of ACP;
hypoposphatasia
decreased levels of ALP;
Hypoadrenalism
increased sodium loss (hyonatremia); increased Mg(2+)
Potassium deficiency
increased sodium loss (hyonatremia)
Ketonuria
increased sodium loss (hyonatremia)
salt-losing nephropathy
increased sodium loss (hyonatremia)
Nephrotic Syndrom
Increased water retention (hyponatremia)
Hepatic Cirrhosis
Increased water retention (hyponatremia); jaundice; increased ALT and AST; normal or mildly elevated ALP; decreased albumin;
SIADH
Water imbalance (hyponatremia); increased ADH (antidiuretic hormone); decreased water excretion; hypervolemia; decreased ECF osmolality
multiple myeloma
hyponatremia; Elevated total protein; Elevated calcium; Low white or red blood cell count; Moderate to large amounts of protein in the urine; large amounts of an abnormal immunoglobulin protein (M-protein); 24 hour Urine free light chains kappa or lambda but not both; monoclonal IgG or IgA; Uric acid levels may be elevated; may be increased
diabetes insipidous
hypernatremia; increased osmolality; impaired secretion of AVP or kidneys cannot respond to AVP;
Hyperaldosteronism
decreased K+, increased Mg(2+) and Na+; hypertension; increased ratio of renin to aldosterone; alkalosis;
Cushings syndrome
decreased K+; moon face; hump on back of neck; 24-hour urinary free-cortisol test increased cortisol; Late-night salivary cortisol test increased cortisol; Low-dose dexamethasone suppression test with no cortisol level drop; Dexamethasone–CRH test; normal or high ACTH;
Waldenstrom macroglobulinemia)
increased monoclonal IgM;
