Complex Lipids and Sphingolipidoses

Vocabulary flashcards covering the biochemical structure, membrane distribution, surfactant functions, and clinical genetics of complex lipids and sphingolipidoses.

Glycerophospholipids

Amphiphilic membrane lipids built on a glycerol backbone where C2 and C3 carry esterified fatty acids, and C1 carries a polar head group composed of phosphate coupled to an alcohol such as choline, ethanolamine, serine, or inositol.

Cytidine Triphosphate (CTP)

The high-energy nucleotide from which the phosphate group in glycerophospholipid biosynthesis is often derived, rather than being derived from ATP.

Phosphatidylethanolamine (Cephalin)

A glycerophospholipid composed of phosphatidic acid (PA) and ethanolamine, which serves as a major constituent of membrane lipids in the inner leaflet of the lipid bilayer.

Phosphatidylcholine (Lecithin)

A glycerophospholipid formed from phosphatidic acid (PA) and choline; it represents a major lipid component of the outer membrane leaflet and is utilized to synthesize lipoproteins, lung surfactant, sphingomyelin, and platelet-activating factor.

Phosphatidylserine

A non-major membrane glycerophospholipid formed by phosphatidic acid (PA) and serine that is localized specifically to the inner leaflet of the plasma membrane.

Phosphatidylinositol

A glycerophospholipid formed by phosphatidic acid (PA) and inositol that is found in the inner leaflet of the plasma membrane but is not a major structural component.

Lung Surfactant

A surface-active lipoprotein complex consisting primarily of dipalmitoyl phosphatidylcholine, phosphatidylglycerol, cholesterol, and surfactant proteins ($\text{Sp-A}$, $\text{Sp-B}$, and $\text{Sp-C}$) that reduces surface tension in alveolar air spaces to prevent alveolar collapse on expiration.

Respiratory Distress Syndrome (RDS)

A condition resulting from insufficient lung surfactant production—common in premature infants and reproducible in adults whose pneumocytes are damaged by chemotherapy or immunosuppressive drugs—causing alveoli to collapse and requiring ten times the normal pressure for re-inflation.

Lecithin/Sphingomyelin (L/S) Ratio

An amniotic fluid marker used to assess fetal lung maturity; a ratio of $2$ or greater indicates pulmonary maturity, typically achieved when phosphatidylcholine concentrations rise relative to sphingomyelin around $35$ weeks of gestation.

Ceramide

A sphingolipid precursor consisting of a sphingosine backbone connected to a fatty acid chain via an amide bond at C2; phosphocholine or carbohydrates attach to its C1 hydroxymethyl group to generate complex sphingolipids.

Sphingomyelin

A sphingolipid composed of ceramide linked to phosphocholine, localized in plasma membranes alongside phosphatidylcholine and highly concentrated in the myelin sheath of nerve fibers and grey matter of the brain.

Lysosomal Storage Diseases

A category of metabolic disorders marked by defective lysosomal degradation pathways, including sphingolipidoses, mucopolysaccharidoses, mucolipidoses, and Pompe disease (type II glycogen storage disease).

Sphingolipidoses

A family of inherited enzyme deficiency disorders characterized by substrate accumulation within lysosomes; all are transmitted in an autosomal recessive manner except for Fabry disease, which is X-linked recessive.

Tay-Sachs Disease

An autosomal recessive sphingolipidosis prevalent in Ashkenazi Jewish populations caused by hexosaminidase A deficiency, causing intracellular accumulation of $\text{GM}_2$ ganglioside, developmental delay, hypotonia, seizures, blindness, and death around age $4$ without hepatomegaly.

Cherry-Red Spot on Macula

A characteristic funduscopic finding seen in Tay-Sachs and Niemann-Pick diseases produced when pale, lipid-engorged retinal ganglion cells surround the normal, thin, vascularized fovea centralis.

Onion-Skin Lysosomes

Multilayered, whorled lysosomal configurations observed under electron microscopy inside neurons, diagnostic of Tay-Sachs disease.

Gaucher Disease

The most common autosomal recessive lysosomal storage disease, caused by a deficiency of $\beta$-glucocerebrosidase leading to glucocerebroside accumulation in the brain, liver, spleen, and bone marrow.

Gaucher Cell

A lipid-engorged macrophage with an enlarged cytoplasm showing a striated, fibrillar texture that resembles 'crumpled tissue paper' on light microscopy.

Erlenmeyer Flask Deformity

A skeletal radiologic abnormality of the distal femur observed in Gaucher disease, caused by extensive defective bone remodeling and expanding marrow infiltration.

Chitotriosidase

A macrophage-produced enzyme whose circulating levels are markedly elevated in patients with Gaucher disease, serving as a functional clinical biomarker.

Krabbe Disease

An autosomal recessive sphingolipidosis caused by a lack of galactocerebrosidase (GALC) activity, triggering toxic buildup of galactocerebroside and psychosine, loss of oligodendrocytes, severe demyelination, developmental regression, and optic nerve atrophy.

Globoid Cell

A large multinucleated macrophage of mesodermal origin found clustered in brain white matter, serving as the diagnostic microscopic feature of Krabbe disease.

Fabry Disease

An X-linked recessive disorder caused by $\alpha$-galactosidase A deficiency that leads to ceramide trihexoside accumulation in vascular endothelial cells, smooth muscle, and organ epithelia.

Angiokeratomas

Punctate, dark red-to-blue vascular cutaneous lesions commonly presenting in a characteristic 'bathing-trunk distribution' in patients with Fabry disease.

Fabry Crises

Recurrent episodes of severe lancinating and burning pain (dysesthesia) affecting the extremities (hands and feet) in individuals with Fabry disease.

FABRYC Mnemonic

A clinical mnemonic for Fabry disease denoting Foam cells, $\alpha$-galactosidase A deficiency / Angiokeratomas, Burning pain in hands and feet, Renal failure, YX genotype (male), and Cardio-Cerebrovascular disease / Ceramide trihexoside accumulation.

Niemann-Pick Disease

An autosomal recessive condition characterized by sphingomyelinase deficiency (Types A and B) or defective NPC proteins (Type C), leading to sphingomyelin accumulation, progressive neurodegeneration, hepatosplenomegaly, and a macular cherry-red spot.

Zebra Bodies

Concentric, palisaded lamellar lysosomal inclusions of myelinoid material visible under electron microscopy within endothelial cells and macrophages in Niemann-Pick disease.

Metachromatic Leukodystrophy

An autosomal recessive lysosomal storage disorder caused by arylsulfatase A deficiency, resulting in the accumulation of cerebroside sulfate and extensive central and peripheral demyelination accompanied by motor regression, ataxia, and optic atrophy.