Lipid metabolism disorder

Toxic accumulation of long chain fatty acids (LCFA) in muscle. Much more severe if cardiac muscle.

Cause: Deficiency or mutation in carnitine; the molecule which transports LCFA across the mito. membrane for oxidation.

Signs: muscle weakness, hypotonia, hypoketotic hypoglycemia, and accumulation of lipid droplets

Lipid metabolism disorder.

Toxic accumulation of fatty acyl-CoA in muscle. Much more severe if cardiac.

Cause: Deficiency or mutation in acyl-CoA dehydrogenase, the first enzyme in beta-oxidation of lipids in the mito. matrix

Signs: Severe hypoglycemia, hypoketonemia, and accumulation of carboxylic acid.

Lipid metabolism disorder

Toxic accumulation of ketone bodies (ketosis) caused by starvation, diabetes, or a high-fat/low-carb diet. Acetone odor on patient's breath.

Peroxisomal lipid metabolism disorder

Very severe disease involving defects in peroxisomal biogenesis. Mainly affects liver and brain.

Peroxisomal lipid metabolism disorder.

Build-up of phytanic acid due to mutation in phytanoyl CoA hydroxylase, leading to reitinitis pigmentosa, ataxia, and polyneuropathy.

Peroxisomal lipid metabolism disorder

Mutation in ABC half-transporter that binds very long chain FA. Affects brain and adrenal cortex.

Lipid metabolism disorder

Defect in methylmalonyl CoA mutase activity (due to lack of B12 coenzyme) leads to build-up of methylmalonyl CoA.

Lipid metabolism disorder

Defect in either lipoprotein lipase (LPL) or ApoCII leads to pancreatitis, hepatospleenomegaly, and xanthomas.

Lipid metabolism disorder

Build-up of extracellular LDL (athersclerotic plaques) due to defects in LDL trafficking by either LDL receptors, Apo B100, PCSK9, or ARH adapter protein. Can be treated by lowering LDL in diet or modulating synthesis and degradation via antioxidants such as vitamin E.

Amino acid metabolism disorder

Fatty liver (decrease in lipoprotein synth), edema, anemia (low Hb) and poor immune system caused by high starch and extreme deficiency in proteins

.

Amino acid metabolism disorder

Overall lack of body mass caused by lack of caloric and protein intake

.

Amino acid metabolism disorder

Reduction in neutral AA absorption caused by a defect in AA transporter

.

Amino acid metabolism disorder

Accumulation of gall stones due to lack of cysteine absorption caused by defect in transport of Cysteine and dibasic AA (Lys, Arg, Orinithine): C-O-L-A

Amino acid metabolism disorder

Accumulation of NH3 leads to widespread CNS effects caused by NH3 reaction with alpha-ketoglutarate (substrate for TCA) to form Glu. Variable causes possible, but most common is Orinithine transcarbamylase (OTC) deficiency, signaled by orotic acid in urine

.

Amino acid metabolism disorder

Odd pigmentation of cartilage and collagenous tissue caused by build up of Homogentisate due to defects in Homogentisate oxidase

.

Amino acid metabolism disorder

Ketoacidosis and retarded growth caused by defect in branched chain AA degradation due to methylmalonyl CoA mutase deficiency

.

Amino acid metabolism disorder

Accumulation of Met and homocysteine, related to increased risk of cardiovascular incidents. Caused by defect in cystathionine beta-synthase or dietary deficiencies in B12 and folate

.

Ethanol metabolism disorder

Lipid accumulation in the liver (fatty droplets) due to NADH-inhibition of beta-Ox, leading to liver cell death.

Ethanol metabolism disorder. Facial deformities and retardation caused by maternal EtOH consumption

.

Ethanol metabolism disorder

Confusion, ataxia, nystagmus, and high cardiac output caused by disruptions in TCA, pentose-phosphate pathway, and AA metabolism due to Vitamin B1 deficiency

.

Alcohol metabolism disorder

Decrease in HDL levels, leading to increased cardiovascular risks caused by chronic alcohol usage.

Lifestyle disorder

Chronic hyperglycemia caused first by insulin resistance and second by secretory defect. Directly caused by obesity.

Lysosomal storage disorder

X-linked recessive defect in alpha-galactosidase A leads to globoside accumulation. Affects PNS, skin, renal, cardiac.

Lysosomal storage disorder

X-linked recessive defect in iduronate-2-sulphatase leads to dermatan and heparan sulfate accumulation. Signaled by organomegaly and skin thickening.

Lysosomal storage disorder

Defect in alpha-iduronidase leads to accumulation of dermatan and heparan sulphate. Same effects as Hunter's (MPS II), in addition to corneal clouding.

Lysosomal storage disorder

Defects in both beta-Hexosaminidase A & B leads to accumulation of GM2 gangliosides and globosides. Phenotypically same as Tay-Sachs, with addition of visceral dysfunction.

Lysosomal storage disorder

Defect in ABC transporter leads to accumulation of LCFA in brain and adrenal cortex.

Lysosomal storage disorder

Defect in integral membrane protein causes accumulation of inclusion bodies containing polysacch. and lipids.

Lysosomal storage disorder

Defect in beta-Hexosaminidase A leads to accumulation of GM2 gangliosides. Signaled by "cherry-red" spot on macula and progressive neurodegeneration.

Amino acid metabolism disorder

Accumulation of phenylalanine, leading to excess phenylpyruvate, caused by deficiency in enzyme phenylalanine hydroxylase, which converts Phe to Tyr

Lysosomal storage disorder

Defect in beta-glucocerebrosidase causes accumulation of glucocerebroside. Most common LSD, affects mainly Ashkenazi Jews. Usually affects CNS.

Lysosomal storage disorder

Defect in sphingomyelinase leads to accumulation of sphingomyelin. Affects NS, spleen & liver.

Lysosomal storage disorder

Defect in arylsulfatase A causes accumulation of cerebroside sulfate. Affects CNS and PNS.

Lysosomal storage disorder

Defect in beta-Galactocerebrosidase causes accumulation of galactocerebroside and galactosylsphingosine. Also called "Globoid cell leukodystrophy" (GLD). Affects NS.

Lysosomal storage disorder

Defect in Ceramidase leads to accumulation of ceramide. Affects skin, joints.

Lysosomal storage disorder

Defect in beta-Galactosidase causes accumulation of GM1 gangliosides. Affects NS.

Cell junction and adhesion disorder

Blistering autoimmune skin disease caused by production of antibodies targeting desomosome-specific cadherhins (desmogleins). Desmosome disruption leads to improper keratinocyte attachments.

Cell junction and adhesion disorder

Variable phenotype, ranging from mild blistering to death. Usually caused by mutation leading to disruption in dermal-epidermal cohesion. Stop codon mutations are more severe than missense. Symptoms can be confined to teeth or nails as well.

Extracellular matrix disorder

Mutation in type IV collagen leads to irregularly thickened and dysfunctinoal glomerular filter, usually leading to kidney failure.

Extracellular matrix disorder

Mutation in type II collagen causes cartilege defects and bone and joint deformities.

Extracellular matrix disorder

Mutation in type III collagen causes overall weakness in blood vessel and organs, often leading to rupture of aorta or intestine. Can be caused by defects in procollagen peptidase or lysyl hydroxylase, usually resulting in joint instabililty and skin hyperelasticity.

Extracellular matrix disorder

Dietary deficiency of vitamin C leads to enzymatic dysfunction of prolyl hydroxylase, causing deficiency in hydroxyproline and progressive collagen degradation.

Autosomal dominant disorder

• Mutation in fibrillin 1 (FBN1)
  • 25-35% de novo
• exhibits pleiotropy - affects multiple systems
  • abnormally elastic connective tissue
  • patients usually tall and lanky
  • can also affect:
    • heart (valve prolapse)
    • eyes (myopia)

Extracellular matrix disorder

Defect in laminin alpha 2 chain in muscle cells leads to disruption of bridge between actin cytoskeleton and ECM (apoptosis).

Vitamin deficiency disorder

1. Usually caused by Folate deficiency
2. Most common vitamin deficiency disorder
3. Affects DNA synthesis and degradation
4. Leads to abnormal erythrocyte production

Vitamin deficiency disorder

1. Affects DNA synthesis and degradation
2. Causes functional folate deficiency
   • cannot de-methylate folate
3. Can give similar phenotype to folate deficiency
   • abnormal erythrocytes
4. Distinguished by:
   •  neurological deficits 
   • increased serum levels of methylmalonyl CoA 
     • B₁₂ catalyzed rxn from odd-chain FA degradation

Nucleotide metabolism disorder

1. Build-up of orotic acid (orotate)
2. Defect in pyrimidine synthesis
3. Distinguished from OTC deficiency by lack of hyperammonemia

Nucleotide metabolism disorder

1. Accumulation of deoxyadenosine
2. Defect in adenosine deaminase
3. Also inhibits ribonucleotide reductase
4. Leads to overall reduction in DNA and immune cell production ===> "bubble boy"

Nucleotide metabolism disorder

1. Defect in hypoxanthine-guanine phosphoribosyl transferase
   • severely affects purine salvage pathway
2. Excess uric acid production (urine)
3. Normal at birth, eventually fatal