ABMGG Medical Biochemical Genetics flashcards

32 cards. Read the term and the definition here. The deck at the top of this page is optional.

Beadle and Tatum principle

One gene–one enzyme concept: each enzyme is encoded by a single gene, so a gene defect blocks one metabolic step, causing substrate accumulation and product deficiency.

Heteroplasmy threshold effect

Mitochondrial DNA mutations exist in mixed wild-type and mutant copies; disease appears only when mutant load exceeds a tissue-specific threshold, often 60–80 percent.

Mannose-6-phosphate targeting

Enzyme replacement therapies are glycosylated with mannose-6-phosphate, which binds receptors on the cell surface and directs enzymes into lysosomes.

Cofactor-responsive enzyme defects

Defects in biotin, thiamine, pyridoxine, cobalamin, or molybdenum metabolism can mimic primary enzyme disorders; cofactor loading may restore activity and treat the disorder.

Residual enzyme activity

Enzyme activity measured in leukocytes or fibroblasts distinguishes classic from variant forms; very low residual activity generally predicts earlier and more severe disease.

Urea cycle hyperammonemia pattern

Hyperammonemia without major acidosis, early respiratory alkalosis, and elevated orotic acid in OTC deficiency versus low orotic acid in CPS1 or NAGS defects.

MCAD deficiency presentation

Fatty acid oxidation defect causing hypoketotic hypoglycemia, hepatomegaly, and elevated C8 and C8:1 acylcarnitines after fasting or illness; risk of sudden death.

Maple syrup urine disease

Branched-chain ketoacid dehydrogenase deficiency causing elevated leucine, isoleucine, and valine, ketoacidosis, encephalopathy, and cerebral edema driven by leucine.

Classic galactosemia

GALT deficiency causing jaundice, hepatomegaly, cataracts, and E. coli sepsis; accumulation of galactose-1-phosphate and galactitol; treated with galactose restriction.

Propionic acidemia features

Organic acidemia with anion-gap acidosis, ketosis, hyperammonemia, and pancytopenia in the newborn period; propionylcarnitine (C3) is elevated.

Zellweger spectrum

Peroxisomal biogenesis disorders with hypotonia, dysmorphism, seizures, and elevated very-long-chain fatty acids; inheritance is autosomal recessive.

Tandem mass spectrometry screening

First-tier newborn screening method measuring amino acids and acylcarnitines from dried blood spots to detect aminoacidopathies, organic acidemias, and fatty acid oxidation defects.

Urine organic acid analysis

GC-MS testing of urine that identifies methylmalonic, propionic, isovaleric, and glutaric acidurias; urine is preferred for volatile organic acids.

Ammonia sample handling

Plasma ammonia must be collected and transported on ice and analyzed promptly, because delayed processing falsely elevates results through red cell ammonia release.

Second-tier newborn screening

Confirmatory molecular, enzymatic, or repeat dried blood spot testing after a positive first-tier screen, improving positive predictive value and reducing false positives.

Acylcarnitine profile interpretation

Specific acylcarnitine species indicate blocks in fatty acid oxidation or organic acid pathways; results are influenced by sample age, hemolysis, and prematurity.

Biotinidase enzyme assay

Colorimetric assay confirming biotinidase deficiency in dried blood or serum; low activity supports diagnosis and predicts response to biotin therapy.

Acute hyperammonemia treatment

Stop protein intake, give IV glucose and lipids, use sodium benzoate and phenylbutyrate as nitrogen scavengers, and consider hemodialysis for refractory severe cases.

Sick-day protocol

Written emergency plan providing extra calories, avoiding fasting, and specifying when to seek care during illness; shared with schools and emergency departments.

PKU dietary target

Low-phenylalanine diet with tyrosine supplementation; plasma phenylalanine targets are typically 120–360 micromol/L in children and higher in adults.

Sapropterin response

Tetrahydrobiopterin analog used in BH4-responsive phenylketonuria; response is determined by a loading test showing reduced plasma phenylalanine.

Maternal PKU teratogenicity

Elevated maternal phenylalanine during pregnancy causes microcephaly, intellectual disability, and congenital heart defects; strict preconception phenylalanine control reduces risk.

Enzyme replacement therapy

Intravenous recombinant enzyme used for non-neurologic lysosomal storage disease such as Gaucher, Fabry, Pompe, and selected mucopolysaccharidoses.

Autosomal recessive recurrence

Carrier parents each pass one pathogenic variant, giving a 25 percent recurrence risk per pregnancy; consanguinity increases carrier frequency for rare disorders.

X-linked metabolic disease

OTC deficiency, Fabry disease, and MPS II are X-linked; hemizygous males are severely affected, and heterozygous females may be affected by skewed X-inactivation.

ACMG variant classification

Five-tier system (pathogenic, likely pathogenic, variant of uncertain significance, likely benign, benign) using population, functional, computational, and segregation evidence.

Gonadal mosaicism

A pathogenic variant present in a subset of a parent's germ cells can cause recurrence of an apparently de novo dominant disorder in subsequent pregnancies.

Mitochondrial inheritance

Mitochondrial DNA is maternally inherited; heteroplasmy and threshold effects produce variable severity and tissue-specific phenotypes among affected relatives.

GINA protections

US law restricting use of genetic information by health insurers and employers; it does not cover life, disability, or long-term care insurance.

Informed consent for testing

Pretest discussion covering purpose, limitations such as variants of uncertain significance, incidental findings, privacy, and implications for family members.

Cascade carrier screening

Testing at-risk relatives after a proband is diagnosed, with pretest counseling about reproductive risk and the possibility of uncertain results.

Duty to warn relatives

Ethical and legal tension between patient confidentiality and warning at-risk relatives; disclosure generally requires consent unless harm is imminent and preventable.