Niemann Pick

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Niemann Pick

  • Synthesis and degradation of phosphoglycerides
    • Phosphoglycerides
      • synthesized by a process similar in its initial steps to triacylglycerol synthesis glycerol 3-phosphate combines with two fatty acyl CoA to form phosphatidic acid
      • Synthesis of phospha tidy linositol
        • Phosphatidic acid reacts with cytidine triphosphate (CTP) to form cytidinediphosphate(CDP)-diacylglycerol, which reacts with inositol to form phosphatidylinositol.
        • Phospha tidy linositol can be further phosphorylated to form phosphatidylinositol 4,5- bisphosphate, which is cleaved in response to various stimuli to form the compounds inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which serve as second messengers.(MCQ)
  • Synthesis of phosphatidyl ethanolamine, phosphatidylcholine, and phosphatidylserine
    • Phosphatidic acid releases inorganic phosphate, and diacylglycerol is produced. DAG reacts with compounds containing cytidine nucleotides to form phosphatidylethanolamine and phosphatidylcholine.
    • Phosphatidyl ethanolamine
      • DAG reacts with CDP-ethanolamine to form phosphatidylethanolamine.
      • Phosphatidyl ethanolamine can also be formed by decarboxylation of phosphatidylserine
    • Phosphatidylcholine
      • DAG reacts with CDP-choline to form phosphatidylcholine(lecithin).(MCQ)
      • Phosphatidyl choline can also be formed by methylation of phosphatidylethanolamine.
      • S-Adenosylmethionine (SAM) provides the methyl groups.(MCQ)
      • Phosphatidylcholine : important functions (MCQ)
        • important component of cell membranes and the blood lipoproteins
        • provides the fatty acid for the synthesis of cholesterol esters in high-density lipoprotein (HDL) by the lecithin:cholesterolacyltransferase (LCAT) reaction (MCQ)
        • as the dipalmitoyl derivative, serves as a component of lung surfactant.
      • If choline is deficient in the diet, phosphatidylcholine can be synthesized de novo from glucose
      • Respiratory distress syndrome (RDS) of the newborn
        • occurs in premature infants(MCQ)
        • due to a deficiency of surfactant in the lungs, which leads to a decrease in lung compliance.
        • Dipalmitoylphosphatidylcholine (DPPC, also called lecithin), is the primary phospholipid in surfactant, which lowers surface tension at the alveolar air–fluid interface.
        • Surfactant is normally produced at gestational week 30(MCQ)
    • Phosphatidylserine
      • Phosphatidylserine is formed when phosphatidylethanolamine reacts with serineSerinereplaces the ethanolamine moiety
  • Degradation of phosphoglycerides
    • Phospho glycerides are hydrolyzed by phospholipases.
      • Phospholipase A1 releases the fatty acid at position1 of the glycerolmoiety
      • Phospholipase A2 releases the fatty acid at position 2
      • Phospholipase C releases the phosphorylated head group (e.g., choline) at position 3
      • Phospholipase D releases the free head group.
  • Synthesis and degradation of sphingolipids
    • Sphingo lipids are derived from serine rather than glycerol.(MCQ)
    • Serine condenses with palmitoyl CoA in a reaction in which the serine is decarboxylated by apyridoxal phosphate–requiring enzyme.
    • The product of the condensation reaction is a derivative of sphingosine. Subsequent reactions convert this product tosphingosine.(MCQ)
    • A fatty acyl CoA forms an amide with the nitrogen of sphingosine, and the resulting compound is ceramide.(MCQ)
  • The hydroxymethyl moiety of ceramide combines with various compounds to form sphingolipids and sphingoglycolipids.
    • Phosphatidyl choline reacts with ceramide to form sphingomyelin.
    • Uridinediphosphate (UDP)-sugars react with ceramide to form galacto cerebrosides  or glucocerebrosides.(MCQ)
  • What are gangliosides
    • A series of sugars can add to ceramide, with UDP sugars serving as precursors.
    • CMP-NANA (N-acetylneuraminic acid, a sialic acid) can form branches from the carbohydrate chain. These ceramide-oligosaccharide compounds are gangliosides.(MCQ)

Sphingolipidoses

    • Sphingo lipids are degraded by lysosomal enzymes.
    • Fabry disease
      • a-Galactosidase A deficiency(MCQ)
      • Glycolipids in brain, heart, and kidney, resulting in ischemia of affected organs
      • Severe pain in the extremities (acroparesthesia), skin lesions (angiokeratomas), hypohidrosis, and ischemic infarction of the kidney, heart, and brain(MCQ)
    • Gaucher disease
      • Gluco cerebrosidase deficiency
      • Gluco cerebrosides in blood cells, liver, and spleen
      • Hepatosplenomegaly anemia, thrombocytopenia, bone pain, and Erlenmeyer flask deformity of the distal femur.
      • autosomal recessive deficiency (MCQ)
    • Metachromatic leukodystrophy
      • Arylsulfatase Adeficiency(MCQ)
      • Sulfated glycolipid (sulfatide) compounds accumulate in neural tissue
      • cause demyelination of central nervous system and peripheral nerves.
      • Clinical consequences of demyelination include loss of cognitive and motor functions, intellectual decline in school performance, ataxia, hyporeflexia, and seizures.
    • Niemann-Pick disease
      • Sphingo myelinase deficiency(MCQ)
      • Sphingo myelin in the brain and blood cells
      • Mental retardation, spasticity, seizures, and ataxia
      • Death usually results by age 2-3 years
      • Inheritance is autosomal recessive.(MCQ)
    • Krabbe disease
      • b-Galactosidasedeficiency(MCQ)
      • Glycolipids causing destruction of myelin-producing oligodendrocytes
      • Clinical consequences of demyelination include spasticity and rapid neurodegeneration leading to death.
      •  Clinical signs include hypertonia and hyperreflexia, leading to decerebrate posturing, blind- ness, and deafness.
      •  Inheritance is autosomal recessive.(MCQ)
    • Tay-Sachs disease
      • Hexosaminidase Adeficiency(MCQ)
      • GM2 gangliosides in neurons(MCQ)
      • Progressive neurodegeneration, developmental delay, and early death.
      • autosomal recessive deficiency (MCQ)


    Rare Diseases Research: Clinical Trial for Niemann-Pick Type C
    Brisan’s Last Morning – A Sweet Laugh | Niemann-Pick Type C
    As you can see, for him… was in a great mood. We didn’t wake up thinking later that evening was his “day”. Many know he had Niemann-Pick Type C disease but sadly he went into septic shock later that afternoon. We are still trying to wrap our minds around this and are working on digging into the real reason he went into septic shock.
    Niemann-Pick Disease Medical Course
    Quinn Linzer on News 12 – Niemann Pick type A
    With so much media attention I wanted to clear up some details to Quinn’s story as the interview doesn’t share the complete story. We did not create Quinn’s list, we asked our family and friends for experiences everyone should have in their lifetime and the list evolved from their suggestions. #1 on this list is to simply be loved, other items are to play with puppys, swing on a swing, other more ambitious activity such as to go to sports game or Disney are only done if Quinn is up to it and adapted to an infant. As she has been sick since birth most of our time is spent at home so when have opportunities to go out she shows her excitement and happiness with the most amazing smiles. Regarding the fundraising, that was taken up by family, friends and generous strangers on their own. We did not request any financial support. We love our daughter so much and treasure every moment we have with her. Thanks for following her story!
    Young girl battles Niemann-Pick Disease