Vitamin Sea
This enzyme, along with lysyl hydroxylase, requires vitamin C as a cofactor to modify collagen's amino acids.
What is prolyl hydroxylase?
This is the drug class pamidronate belongs to.
What are bisphosphonates?
This is the most abundant type of collagen found in bone.
What is type I collagen?
This blue discoloration of the eye's outer coat was found on Omar's physical exam and is classic for OI.
What is blue sclera?
Dr. Iqbal initially declined to order this test up front, since Omar's clinical picture alone was enough to diagnose him and it wouldn't have changed his treatment.
What is genetic testing?
Humans lack this enzyme, which is why — unlike most mammals — we must get vitamin C from our diet.
What is L-gulonolactone oxidase?
Pamidronate binds with high affinity to this mineral component of bone.
What is hydroxyapatite?
This repeating three-residue amino acid motif characterizes the collagen protein sequence.
What is Gly-X-Y?
This dental finding — yellow-brown, translucent teeth — was noted on Omar's exam.
What is dentinogenesis imperfecta?
This type of nucleotide substitution — a guanine swapped for a cytosine — occurred in Omar's COL1A2 gene.
What is a transversion?
This deficiency disease, marked by bleeding gums and poor wound healing, results from inadequate vitamin C.
What is scurvy?
This enzyme of the mevalonate pathway is inhibited by nitrogen-containing bisphosphonates like pamidronate.
What is farnesyl pyrophosphate synthase (FPPS)?
This gene, along with COL1A2, most commonly carries mutations that cause osteogenesis imperfecta.
What is COL1A1?
This inheritance pattern best explains why Omar's mother, uncle, and maternal grandmother were all affected by "brittle bones."
What is autosomal dominant?
This amino acid replaced glycine in Omar's collagen chain, disrupting normal triple-helix folding.
What is alanine?
This route of administration bypasses the body's normal tight homeostatic control of vitamin C, allowing much higher plasma levels than oral dosing.
What is IV (intravenous) administration?
This flu-like reaction commonly follows a patient's first pamidronate infusion and self-resolves in a few days.
What is the acute phase reaction?
This is the level of protein structure — the linear amino acid sequence — that was altered by Omar's mutation.
What is primary structure?
This is the mildest Sillence classification type of osteogenesis imperfecta — the type Omar was ultimately diagnosed with.
What is Type I?
Despite suspecting Omar's fractures were not the result of abuse, this is the type of consultation Dr. Jones sought to clarify his legal reporting responsibilities.
What is a legal/mandatory-reporting consult?
Patients with this red blood cell enzyme deficiency are at risk of hemolysis with high-dose vitamin C.
What is G6PD deficiency?
This is the bone cell type that pamidronate ultimately drives to apoptosis, reducing bone resorption.
What is the osteoclast?
This small amino acid must occupy every third position in collagen's sequence to allow tight triple-helix folding.
What is glycine?
Omar's normal alkaline phosphatase level helped rule out this rare metabolic bone disease, which classically presents with low ALP, blue sclerae, and fractures — making it a key mimicker of OI.
What is hypophosphatasia?
This is the emotional reaction Mrs. Shah had upon learning she may have passed OI to Omar, prompting Dr. Iqbal to offer reassurance and resources.
What is guilt (self-blame)?