Abstract| Volume 177, ISSUE 1, P41, August 2013

Catecholamine Disorders and Hereditary Sensory and Autonomic Neuropathy

      Hereditary disorders affecting catecholamine metabolism or development of sensory and autonomic neurons manifest with a wide range of autonomic disturbance. Genetic catecholamine disorders include deficiencies of tyrosine hydroxylase (TH), tetrahydrobiopterin (BH4), L-amino acid decarboxylase (L-ADCC), dopamine-beta-hydroxylase (DBH), vesicula monoamine transporter (VMAT) 2, and norepinephrine transporter (NET). BH4, L-ADCC and VMAT2 deficiency have similar manifestations; autonomic symptoms include hypersalivation, temperature instability, and pupil abnormalities, associated with various motor (eg, dystonia) and behavioral abnormalities. DBH deficiency manifests neonatally with hypotension, hypothermia, hypoglycemia, vomiting and dehydration; orthostatic hypotension is the major manifestation in childhood and later. NET deficiency produces orthostatic intolerance with postural tachycardia. Hereditary sensory and autonomic neuropathies (HSANs) are a heterogenous group of disorders that present with sensory loss and variable degrees of motor and autonomic involvement. Autosomal dominant HSANs include HSAN-1 (due SPTLC1 mutations), Charcot-Marie-Tooth (CMT) disease 2B (due to Rab7 mutations), and HSAN-1 with dementia and hearing loss (linked to DNTM1 mutations). HSAN-1 has a juvenile-to-adult onset sensory neuropathy with minor autonomic involvement; CMT2B has prominent motor manifestations. Autosomal recesssive forms include HSAN-II (linked to mutations in the WNK1, FAM134B, or KIF1A genes), HSAN-III (linked to IKBKAP mutation), HSAN-IV (linked to NTRK1 mutations), HSAN-V (linked to NGFB mutations), and HSAN with spastic paraplegia (linked to CCT5 mutations). Autosomal recessive HSANs have onset at birth or in early childhood and have prominent autonomic symptoms. In particular, HSAN-III (familial dysautonomia or Riley-Day syndrome) is characterized by severe small fiber sensory loss and life-threatening autonomic dysfunction. Prominent manifestations include absence of cold and pain sensation, temperature instability (hypothermia and excessive perspiration), blood pressure lability (due to impaired baroreflex afferent function), abnormal swallowing, vomiting crises, and recurrent bouts of aspiration pneumonia. HSAN-IV and HSN-V are characterized by congenital insensitivity to pain and reduced or absent sweating.
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