Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report

BMC Neurology, Oct 2016

Background 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. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. Case presentation Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the “stocking and glove distribution” but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. Conclusions This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://www.biomedcentral.com/content/pdf/s12883-016-0727-8.pdf

Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report

Yamada et al. BMC Neurology Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report Keiko Yamada 0 Junhui Yuan Tomoo Mano Hiroshi Takashima Masahiko Shibata 0 1 0 Center for Pain Management, Osaka University Hospital , 2-15 Yamadaoka, Suita-shi, Osaka 565-0871 , Japan 1 Department of Pain Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita-shi, Osaka 565-0871 , Japan Background: 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. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. Case presentation: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the “stocking and glove distribution” but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. Conclusions: This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation. Hereditary sensory and autonomic neuropathies; Arthropathy; Demyelinating diseases; Acetaminophen; Case report - Background Hereditary sensory and autonomic neuropathies (HSANs) are clinical and genetic disorders of the peripheral nerve [1]. HSANs are linked to 12 genes and have been classified into types I–V on the basis of age at onset, mode of inheritance, and predominant clinical symptoms [1]. Patients with HSAN type II present with loss of pain, temperature, and touch and mutations in the hands and feet [1]. Autonomic disorder is not a dominant feature of HSAN type II, although this disease is called “hereditary sensory and autonomic neuropathy” [1]. HSAN type II, with mutation in the nervous system-specific HSN2 exon of the withno-lysine(K)-1 (WNK1) gene (HSN2/WNK1), is a very rare autosomal recessive disease. A few cases of WNK1/HSN2 have been reported among the following ethnic groups: French–Canadian families (c.594delA, c.918_919insA, c.943c > T) [2, 3], a Lebanese family (c.947delC) [4], and two British families (c.60_61delTG + c.1168_1171delACAG and c.1168_1171delACAG + c.1168_1171delACAG) [5] and in Austrian (c.550C > T) [6], Italian (c.255delC, c.1089_1090insT) [6], Belgian (c.1064_1065delTC) [6], Polish (c.539_540delAG, c.2897_2898delAG) [7], Korean (c.1134_1135insT, c.217C > T) [8], and Japanese (c.1134_1135insT) [9] ethnicities. With the exception of dry hands in a Korean case, autonomic complications have not been reported in patients with HSAN type II with HSN/WNK1 mutation [8]. Charcot arthropathy includes deforming and destructive process in joints and is one of the complications of neurosensory disorders [10]. The lack of protective sensation in patients with sensory neuropathies could cause delayed identification of bone injuries by overload [10]. Because of the lack of sensation experienced by patients with Charcot arthropathy, they are not expected to experience much pain despite severe deformation. However, a previous study reported that among 55 patients with Charcot arthropathy, more than 75 % complained of pain in the foot at the final stage of deformation, although all patients had clinical loss of sensation [11]. The reasons for this remain unclear. Case presentation A 54-year-old woman presented with loss of touch, temperature, position, and vibra (...truncated)


This is a preview of a remote PDF: http://www.biomedcentral.com/content/pdf/s12883-016-0727-8.pdf

Keiko Yamada, Junhui Yuan, Tomoo Mano, Hiroshi Takashima, Masahiko Shibata. Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report, BMC Neurology, 2016, pp. 201, 16, DOI: 10.1186/s12883-016-0727-8