Instituut voor Neuropathische Pijn

HSAN: 5 typen

Er zijn 5 verschillende typen van de erfelijke sensibele en autonome neuropathieen, de hereditary sensory autonomic neuropathy (HSAN). Hier een tabel die deze 5 types beschrijft.  De verschillende soorten van erfelijke autonome neuropathieen zijn zeldzaam, Naast de familiare amyloid polyneuropathie is de erfelijke sensibele en autonome neuropathie een voorbeeld daarvan. Andere vormen zijn de ziekte van Fabry disease en de porphyrie. Bij al die ziektes komen ontregelingen voor van het autonome zenwustelsel.  HSAN Mode of Inheritance Onset Symptoms Signs Type I Autosomal dominant, point mutations in SPT, 9q22.1-9q22.3 Second decade of life Distal lower-limb involvement, ulceration of the feet, particularly the soles Low sensory action potential amplitude Type II, Morvan disease Autosomal recessive Congenital onset Pansensory loss of upper and lower limbs, also trunk and forehead; early ulcers Loss of myelinated and unmyelinated fibers Type III, Riley-Day syndrome or familial dysautonomia) Autosomal recessive, 9q31 Childhood onset, predominantly Ashkenazi Jews Pallor in infancy, irregularities in temperature and blood pressure; Difficulties in eating and swallowing Absence of unmyelinated fibers Type IV Autosomal recessive, 1q21-1q22 Congenital onset Widespread anhidrosis, lost sense of pain, mental retardation Loss of myelinated and small unmyelinated fibers Type V Autosomal recessive Congenital onset Pain insensitivity in extremities Not applicable   Voor elk type zijn uitgebreide technische bescrhijvingen op het internet te vinden.   Zo ook het volgende voorbeeld vand e HSAN type 1, die zich kenmerkt door een afwezigheid van pijn en temperatuur gevoel door de degeneratie van de dunne vezels:   Hereditary Sensory Neuropathy I (HSAN I; HSN I)    l Serine palmitoyltransferase, long-chain base subunit 1 (SPTLC1) ; Chromosome 9q22.1-q22.3; Dominant Genetics Misense mutations identified: C133Y, C133W, V144D, Ala352Val + S331F: Severe, early onset disease Founder effect in Australian & English families Serine palmitoyltransferase (SPT) enzyme: Sphingolipid biosynthesis Catalyzes pyridoxal-5'-phosphate-dependent condensation of L-serine & palmitoyl-CoA to 3-oxosphinganine Mutation effects Increased Glucosyl ceramide synthesis: ? Leads to apoptosis Reduced serine palmitoyltransferase activity Normal levels of protein Accumulation of abnormal toxic metabolites4 Deoxy-sphingoid bases (DSB): 1-deoxy-sphinganine & 1-deoxymethyl-sphinganine DSBs have neurotoxic effects on neurite formation in vitro Clinical features Onset: 2nd decade or later; Average 25 years Distribution: Distal > proximal; Symmetric; Legs > Arms sensory, autonomic & reflex loss Sensory Loss: Pain & Temperature (Small fiber); Large fiber loss also occurs Spontaneous sensations: Paresthesias are Rare; Lancinating pains in some kindreds; Burning pain in some Charcot's joints (Neurogenic osteoarthropathy) Progression: Succession of exacerbations Location: Feet, Severe mutilation & shortening; Occasional hands, Thickened fingers X-rays: Distal demineralization; Metatarsal tapering (Licked candy-stick) Weakness Common late in course Distal Autonomic involvement Rare Occasional: Horner syndrome Sensorineural deafness: Variably present Skin: Blistering; Edema & discoloration of foot; Chronic ulcers; Painless injuries Time course: Slow progression Laboratory Electrophysiology: Loss of C > Aδ & Aα axons Immune: Increased Synthesis of IgA Pathology Loss of dorsal root ganglion cells & later motor neurons Predominant loss of small myelinated & unmyelinated axons No CNS changes Er zijn verschillende varianten, afhankelijk van welk gen precies aangedaan is, waarbij bijvoorbeeld pijnloosheid bestaat. Hier twee voorbeelden van deze zeldzame ziekte:   1. Mutatie van het gen SCN 9A   Congenital inability to experience pain   l SCN 9A; Chromosome 2q31-32; Recessive Genetics Mutations: Homozygous nonsense; S459X, I767X, W897X Allelic with: Erythromelalgia; Paroxysmal Extreme Pain Disorder SCN 9A protein: See SCN 9A & Erythromelalgia Onset: Congenital Clinical Sensory Inability to feel pain Over all body regions Painless injuries present Normal: Touch; Temperature (warm & cold); Proprioception; Tickle; Pressure Motor: Normal strength Tendon reflexes: Normal Sweating: Present Bladder function: Normal Laboratory Nerve conduction studies: Normal Nerve biopsy: Normal CNS MRI: Normal 2. Mutatie van een ander gen: Arg211Trp   Hereditary sensory neuropathy with loss of pain perception   l Nerve growth factor-b; Chromosome 1p13.1; Recessive Genetic: Mutation Missense: Arg211Trp NGF-b protein Neurotrophin family Functions: Role in development & maintenance of sympathetic & sensory nervous systems Cellular location: Secreted Epidemiology: Northern Swedish family Clinical: Variable degrees of severity Onset: Early childhood to adult Sensory loss Pain perception: Reduced Temperature: Reduced Skeletal: Charcot joints & Fractures Onset: Childhood or Adult (3rd & 4th decade) Lower extremities: Feet; Ankles; Knees Autonomic Sweating: Normal Fainting: 1 patient GU & GI disorders: 1 patient Laboratory Electrophysiology Nerve conduction velocity: Normal Sensory loss: Temperature ± Vibration R-R interval: Normal Nerve pathology Axon loss: Thinly myelinated & Unmyelinated Less axon loss in adult onset cases   Bron diagram: http://emedicine.medscape.com/article/1173756-overview#Table1  Bron overzichten:  http://neuromuscular.wustl.edu/sensory-small.html#hsnngf Maart 2010, prof.dr. Jan M. Keppel Hesselink