Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration.
Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase.
Insensitivity to pain is a rare disorder that is commonly associated with Hereditary Sensory and Autonomic Neuropathies (HSAN I-V) resulting often in autonomic dysfunction and premature death.
So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP).
Pain insensitivity in humans can be attributed to hereditary sensory and autonomic neuropathies (HSAN) of which there are five classes (HSAN I - HSAN V).
Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma.
Certain forms of hereditary sensory and autonomic neuropathy, especially hereditary sensory and autonomic neuropathy type I, which has minimal autonomic involvement and is more accurately termed hereditary sensory neuropathy type I, can present in a very similar fashion to certain forms of Charcot-Marie-Tooth disease (Charcot-Marie-Tooth type 2B, see below), and therefore it is important that clinicians who regularly manage patients with neuropathy are familiar with the latest developments in the hereditary sensory and autonomic neuropathies.
Here, we demonstrate that defects in the ER fusion protein ATL3, which were identified in patients suffering from hereditary sensory and autonomic neuropathy, result in an increased number of ER-mitochondria contact sites both in HeLa cells and in patient-derived fibroblasts.
Moreover, 2 hereditary sensory and autonomic neuropathies type 1 (HSANI)-associated mutations of ATL3 (Tyr192Cys and Pro338Arg) impair ATL3's binding to GABARAP and function in reticulophagy.
Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules.
We report on the extensive phenotypic characterization of five Italian patients from four unrelated families carrying dominant heterozygous DNMT1 mutations linked to two distinct autosomal dominant diseases: hereditary sensory and autonomic neuropathy with dementia and hearing loss type IE (HSAN IE) and autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN).
Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system that predominantly affect the sensory and autonomic neurons.
We present two generations of a single family with Ser384Phe mutation in the SPTLC2 gene located on chromosome 14q24 characterized by a typical HSAN-1c presentation, with additional findings upper motor neuron signs, early demyelinating features on nerve conduction studies, and type II juxtafoveal retinal telangiectasias also known as macular telangiectasias (MacTel II).
An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12.
FD is classified as a hereditary sensory and autonomic neuropathy (HSAN type III) and is both a developmental and a progressive neurodegenerative condition that results from an autosomal recessive mutation in the gene IKBKAP, also known as ELP1.
Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase.
Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution.
So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP).
Complete prevention of pain has so far been seen in six distinct rare hereditary syndromes, namely the 'channelopathy-associated insensitivity to pain', caused by 13 currently identified variants in the SCN9A gene coding for the alpha-subunit of the voltage-gated sodium channel, and five maladies belonging to the hereditary sensory and autonomic neuropathy (HSAN) I-V syndromes, caused by various mutations in several genes.