(Choice A) Premature coronary artery disease is seen with familial hypercholesterolemia. Cholesterol deposits can lead to tendon xanthomas, xanthelasmas (ie, eyelid plaques), and/or corneal arcus (ie, gray ring around the cornea) but not coarse facial features, intellectual disability, or a diffuse corneal haze.
(Choice B) Accumulation of glucocerebroside within mononuclear cells is seen in Gaucher disease, an autosomal recessive defect in beta-glucocerebrosidase. This condition is characterized by bruising due to thrombocytopenia, hepatosplenomegaly, progressive neurologic deterioration, and severe bone pai n. Premature coronary artery disease does not occur.
(Choice C) Glycogen storage diseases cause defective metabolism of glycogen in the liver and/or muscles. The presentation can include hypoglycemia, lactic acidosis, hepatomegaly, growth retardation, and/or muscle fatigue/cramping. Cardiomegaly can occur with Pompe disease, but corneal clouding is not a feature.
(Choice E) Niemann-Pick disease results from a deficiency of sphingomyelinase, which leads to the accumulation of sphingomyelin within phagocytes. This disease is characterized by hepatosplenomegaly and progressive neurologic deterioration, but eye findings include a cherry-red spot on the macula, not corneal clouding.

(Choice B) Glucose-1-phosphate generated by glycogenolysis is converted by phosphoglucomutase to glucose-6-phosphate. Unlike myophosphorylase, phosphoglucomutase is present in both skeletal muscle and liver. Phosphoglucomutase deficiency is extremely rare, presenting with muscle weakness and fasting hypoglycemia.
(Choice C) Gluoose-6-phosphate is converted to 6-phosphogluconate through a series of reactions by glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase in the pentose phosphate pathway. This pathway maintains adequate levels of reduced glutathione, which is needed to protect from oxidative injury (eg, prevent red cell hemolysis ).
(Choice D) Glucose-6-phosphate is converted to fructose-6-phosphate by glucose-6-phosphate isomerase during glycolysis. A deficiency here would disrupt glycolysis, affecting cells that rely on it as their energy source (eg, red blood cells). Patients have chronic hemolytic anemia.
(Choice E) Within the liver and kidney, glucose-6-phosphatase converts glucose-6-phosphate to glucose to help maintain blood glucose levels during fasting. A deficiency here leads to glycogen storage disease type I (von Gierke disease), presenting in infancy with hypoglycemia.

(Choice A) Steroid hormones, thyroid hormone, and vitamin D act by binding to intracellular receptors with DNAbinding domains that interact with the regulatory DNA sequences of target genes.
(Choice C) Transmembrane ligand-gated ion channels (ionotropic receptors) allow a regulated flux of calcium, sodium, potassium, and chloride ions across the cell membrane. Neurotransmitters that work via ion channellinked receptors include acetylcholine, serotonin, N-methyl-0-aspartate, and gamma-aminobutyric acid.
(Choice D) Insulin and insulin-like growth factor work by stimulating transmembrane receptors with intrinsic tyrosine kinase activity in the intracellular domain, initiating a downstream phosphorylation cascade.
(Choice E) Janus kinase (JAK) is a cytoplasmic protein activated by ligand binding to transmembrane receptors. JAKs activate cytoplasmic transcription factors called signal transducers and activators of transcription (STAT), which enter the nucleus to promote gene transcription. Examples of hormones using a JAK/STAT messenger system include erythropoietin, growth hormone, and prolactin.