Inborn Errors of Metabolism Flashcards
What enzyme is deficient in tyrosinemia type 1? What are the symptoms/signs?
Fumarylacetoacetic acid hydrolase; kidney and liver disease
What are organic acids?
Intermediates in the catabolism of amino acids, lipids, and other compounds
What is the name of methylmalonic acidemia due to a defect in B12 metabolism?
Cobalamin C disorder
What biochemical step is blocked in methylmalonic acidemia? What vitamin is necessary for this step?
The conversion of methylmalonyl CoA to succinyl CoA; B12
What is the typical presentation of McArdle’s disease?
Only muscle involvement
What gene product is mutated in GSD Ib
Glucose-6 phosphate transporter
What is the main symptom associated with glutaric acidemia type 1?
Dystonic movements
What is the mode of inheritance for hereditary fructose intolerance
Autosomal recessive
What symptoms are associated with classical galactosemia?
Vomiting, diarrhea, lethargy, liver disease, jaundice, renal tubular disease, acidosis, cataracts, sepsis
What is the key thing to clinically recognize in organic acidemias?
Wide anion gap ketoacidosis
What lab test result would indicate glycine encephalopathy?
Increased CSF/plasma glycine ratio
What are the symptoms associated with albinism?
Hypopigmentation of skin, hair, and eyes, and reduced visual acuity
What biochemical processes occur in the peroxisomes?
Oxidation of very long chain fatty acids, phytanic acid and pristanic acid oxidation, lysine catabolism, bile acid synthesis, plasmalogen synthesis
What are the laboratory presentations associated with organic acidemias?
Metabolic acidosis, increased anion gap, ketosis, +/- elevated ammonia level
What organ system is affected by Morquio?
Skeletal
How is diagnosis of fatty acid oxidation disorders made?
Plasma acylcarnitine profile
What is the key laboratory pattern for fatty acid oxidation disorders?
Hypoglycemia with inappropriately low ketones and metabolic acidosis
Which urea cycle disorders are x-linked?
Only ornithine transcarbamylase deficiency
What enzyme is deficient in citrullinemia?
Arginosuccinic Acid Synthase
What enzymatic deficiency results in classical galactosemia?
Galactose-1-phosphate uridyltransferase deficiency
Which biochemical step is blocked in homocystinuria? What enzyme catalyzes this step and what vitamin is required?
The conversion of homocysteine to cystathionine is blocked; cystathionine synthase and B6
What is the enzymatic deficiency associated with Hunter syndrome?
Iduronate sulfatase
What symptoms are associated with homocystinuria?
Marfanoid habitus, tall stature, long fingers, long arm span, pectus deformity, downward dislocated lenses, intellectual disability, risk of thromboses
What is the mode of inheritance for maple syrup urine disease?
Autsomal recessive
What enzymatic deficiency is the basis of Von Gierke (GSD Ia)?
Glucose-6 phosphate dehydrogenase
What is the mode of inheritance for Hunter syndrome?
X-linked
How is the anion gap affected in organic acidemias?
Wide anion gap
What symptoms are associated with glycine encephalopathy?
Hypotonia, encephalopathy, seizures, burst surpression EEG
What amino acids’ metabolism is affected by Maple Syrup Urine Disease?
Valine, Isoleucine, Leucine
What symptoms are associated with Smith-Lemli-Opitz Syndrome?
Failure to thrive, syndactyly 2nd-3rd toes, polydactyly, cleft palate, pyrolic stenosis, heart defects, ambiguous genitalia, intellectual disabilities
What enzyme deficiency is the basis of tyrosinemia type 2?
Tyrosine aminotransferase
What is the most comon fatty acid oxidation disorder?
Medium Chain AcylCoA Dehydrogenase Deficiency
What enzymatic deficiency is the basis of phenylketonuria?
Phenylalanine hydroxylase
What symptoms are associated with hereditary fructose intolerance?
Liver/kidney damage, hypoglycemia, vomiting, lethargy, coma
What is the treatment for Maple Syrup Urine Disease?
Diet with restricted leucine, isoleucine, and valine
What condition results from defect in the conversion of glycine to NH3 and CO2?
Glycine encephalopathy
What abnormal lab findings are associated with D-bifunctional protein deficiency?
Elevated very long chain fatty acids, pristanic and phytanic acids, bile acid intermediates
What molecules would be evelated in a plasma amino acid screening for homocystinuria?
Methionine and homocysteine would be elevated
What is the most common urea cycle disorder?
Ornithine transcarbamylase deficiency
What compounds would be abnormal in a plasma amino acid screen?
Arginosuccinic acid and citrulline
What symptoms are associated with Niemann-Pick Disease Type A?
Developmental regression and neurological problems, cherry macula, hepatosplenomegaly,
What are the typical symptoms of GSD I?
Hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, puffy cheeks
What symptoms are associated with tyrosinemia type 2?
Corneal ulcers, skin/CNS involvement
What developmental defects can result from maternal PKU?
Micrcephaly and congenital heart disease
What is the mode of inheritance for Glycine encephalopathy?
Autosomal recessive
What would be elevated in a plasma amino acid screening in a patient with citrullinemia?
Citrulline
What is a feature of GSD Ib but not Ia
Neutropenia
What is the typical presentation of Brancher deficiency (GSD IV)
Fatal liver disease
What biochemical step is blocked in propionic acidemia? What vitamin is necessary for this step?
The conversion of propionyl CoA to methylmalonyl CoA; biotin
What abnormal lab findings are associated with Smith-Lemli-Opitz syndrome?
Low cholesterol, elevated 7-dehydrocholesterol
What are the clinical problems of PKU if left untreated?
Brain damage, deficient production of neurotransmitters, hypopigmentation
What biochemical step is blocked in glutaric acidemia type 1? What vitamin is required as a cofactor?
The conversion of glutaryl CoA to acetyl CoA; riboflavin
What is the typical presentation of Sanfilipo Syndrome?
Developmental delay, behavioral problems, neurological regression
What enzyme is deficienct in Pompe disease (GSD II)?
Alpha glucosidase
What enzyme is deficient in arginosuccinic aciduria?
Arginosuccinic Acid Lyase
What lab results are associated with urea cycle disorders?
Respiratory alkalosis and hyperammonemia
What compounds would be abnormal in the urine of a patient with Hurler syndrome?
Dermatan and heparan sulfate
What disorders are associated with a cherry red macula?
Niemann-Pick A, GM1 gangliosidosis, Tay-Sachs, Sandhoff disease, Farber’s, Sialidosis
What is the enzyme deficiency associated with Hurler syndrome?
Alpha L-iduronidase
What is the anion gap?
Measured cations- measured anions
What symptoms are associated with Pompe disease?
Weakness, hypotonia, cardiomyopathy, abnormal EKG
What is the mode of inheritance for classical galactosemia?
Autsomal recessive
How are specific diagnoses of organic acidemias made?
Urine organic acids profile
What are organic acidemias?
Diseases due to defects in the enzymatic conversion of organic acids into Kreb Cycle components
