Hereditary Sensory and Autonomic Neuropathie Type 1, HSAN1 - SPTLC1, SPTLC2

Klinische Symptomatik

Common symptoms of HSAN are loss of nociception and temperature sense combined with autonomous dysfunction. Autonomous signs may, however, be absent; the disease is therefore also referred to as HSN.
HSAN type 1 begins at the distal ends of the lower extremities. Age of onset is between the second and fourth decade of life. Motor impairment is absent or mild. Patients initially experience paresthesia as well as sensory loss affecting nociception and temperature sense. Touch sense and deep sensation impairment follow, usually less pronounced. Autonomous disturbances like anhydrosis, toe ulcerations, osteoporosis, osteolysis, and mutilation are typical. Bladder and bowel function remains unaffected. Skeletal anomalies like scoliosis or spina bifida are frequently observed.

Genetik

HSAN 1 is caused by mutations in the SPTLC1 gene (Serin Palmitoyltransferase, Long-Chain subunit 1) located on chromosome 9q22.31. Serin Palmitoyltransferase (SPT) is the key enzyme in sphingolipide biosynthesis. It catalyzes the pyridoxal-5'-phosphate dependant condensation of L-Serin and Palmitoyl-CoA to 3-Oxosphinganin. HSAN 1 follows an autosomal dominant pattern of inheritance.

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Diagnostik