Biochem Diseases

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glycogen storage diseases; main theme of this class, inheritance, names and deficient enzymes

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-theme: abnormal glycogen breakdown and accumulation of glycogen within cells
-all are AR
1) von gierke's dz (aka type I)--glucose-6-phosphatase
2) pompe's dz (aka type II)--lysosomal alpha-1,4-glucosidase (aka acid maltase)
3) cori's dz (aka type III)--debranching enzyme aka alpha-1,6-glucosidase
4) mcardle's dz (aka type V)--skeletal muscle glycogen phosphorylase

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von gierke's disease

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-aka type I glycogen storage dz
-deficiency of glucose-6-phosphatase
-cant convert the glu-6-P from glycogenolysis to glu
-severe fasting hypoglycemia
-increased glycogen and glu-6-P in the liver and hepatomegaly
-increased blood lactate
-no increase in serum glucose with glucagon challenge

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pompe's disease

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-aka type II glycogen storage dz
-deficiency of lysosomal alpha-1,4-glucosidase aka acid maltase
-lysosomes cant degrade glycogen into glucose, glycogen accumulates in lysosomes in all organs
-cardiomegaly/restrictive heart dz, hepatomegaly, early death

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cori's disease

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-aka type III glycogen storage dz
-deficiency in debranching enzyme aka alpha-1,6-glucosidase
-cant convert limit dextrans (4 glucoses in a branched configuration from glycogenolysis) into glucose
-generally mild sx because gluconeogenesis is intact (glu-6-phosphatase intact)
-mild fasting hypoglycemia, no increase in serum lactate

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mc ardle's disease

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-aka type V glycogen storage dz
-deficiency in skeletal muscle glycogen phosphorylase (first enzyme in glycogenolysis)
-increased glycogen in muscle but cant break it down
-painful muscle cramps, weakness and myoglobinuria (red pee) with exercise
-no increase in lactic acid with exercise cause the muscle run out of glucose

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hartnup disease

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-AR, defective neutral amino acid transporter in SI and kidneys
-sx: aminoaciduria, cerebellar ataxia, pellagra (vit b3/niacin deficiency; dermatitis, diarrhea, dementia)

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alport's syndrome

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-XD
-hereditary glomerulonephritis
-sensorineural hearing loss

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vitamin D-resistant rickets

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-XD
-defect in renal and GI reabsorption of phosphate
-defective bone mineralization (rickets, osteomalacia)

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lesch-nyhan syndrome

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-XR deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
-HGPRT is a purine salvage enzyme that converts hypoxanthine--> IMP, and guanine--> GMP
-mental retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

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alkaptonuria/ochronosis

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-AR deficiency of homogentisic acid oxidase in the tyrosine degredation pathway
-black cartilage, connective tissue, spots on sclera
-urine turns black on standing
-arthralgias

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galactosemia

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-AR deficiency in galactose 1-phosphate-uridyltransferase (GALT)
-GALT normally converts galactose-1-P to glu-1-P
-cataracts, hepatosplenomegaly, cirrhosis, mental retardation
-tx: galactose + lactose free diet (no dairy!)
-damage caused by accumulation of toxic substances (galactiol)

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hereditary fructose intolerance

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-AR deficiency in aldolase B
-fru-1-P accumulates decreasing available P
-lack of P inhibits glycogenolysis and gluconeogenesis
-hypoglycemia, jaundice, cirrhosis, vomiting, renal disease
-tx: no fructose and sucrose intake

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essential fructosuria

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-defect in fructokinase
-benign, asx
-fructose appears in serum and urine

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homocystinuria

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-3 forms, all AR
-all result in excess homocysteine and cysteine become an essential amino acid
-mental retardation, atherosclerosis, vessel thrombosis, osteoporosis, tall stature, kyphosis, lens subluxation
1) cystathionine synthase deficiency (CS is first enzyme in homocysteine-->cystathionine-->cysteine)
2) decreased affinity of cystathionine synthase for its cofactor pyridoxal phosphate (B6)
3) homocysteine methyltransferase deficiency (along with B12 converts homocysteine-->methionine)

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maple syrup urine disease

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-AR deficiency of branched chain alpha-ketoacid dehydrogenase
-blocked degradation of branched amino acids (ile, val, leu)
-increased leu in the blood
-mental retardation, seizures, feeding problems, sweet-smelling urine, death

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cystinuria

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-defect in renal tubular amino acid transporter
-excess cystine in urine leads to precipitation of cystine kidney stones (staghorn calculi)
-tx: acetazolamide to alkalinize urine

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phenylketonuria

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-AR deficiency in phenylalanine hydroxlase
-PH normally converts phenylalanine--> tyrosine
-accumulation of phenylketones leads to mental retardation, microcephaly, growth retardation, musty odor, eczema
tx: no dietary phenylalanine, supplement tyrosine (now and essential amino acid)