Background: Small fiber neuropathy (SFN) is a disorder selectively affecting small diameter myelinated A-delta and unmyelinated C peripheral nerve fibers. (1) Damage to small somatic nerve fibers results in pain, burning, tingling, or numbness that typically affects the limbs in a distal-to-proximal gradient. In rare cases, small fiber neuropathy follows a non-length-dependent distribution in which symptoms may manifest predominantly in the arms, face, or trunk. (2) SFN has been associated with many medical conditions, most commonly glucose dysmetabolism, but also dysthyroidism, vitamin B12 deficiency, HIV, hepatitis C virus infection, celiac disease, neurotoxic drug exposure, hereditary diseases, and paraneoplastic syndrome. (1) One of the more atypical associated causes of small fiber neuropathy includes a rare renal tubular disorder: Gitelman Syndrome. This autosomal recessive salt-losing tubulopathy is caused by mutation in genes encoding the sodium chloride co-transporters and magnesium channels. (3, 4) The following patient presented with small fiber neuropathy not only of atypical origin but also in an equally uncommon distribution making for a unique and challenging diagnostic process.
Case Description: The authors report a case of a 36-year-old female patient who initially was referred to our pain clinic for evaluation and treatment of fibromyalgia. She described her pain as an electric or burning sensation with insidious onset over several months, first appearing bilaterally in her lower extremities and then spreading to her upper extremities and eventually affecting her back, neck and trunk. The patient’s history was notable for an unintentional 70-kilogram weight loss over a year, despite a normal appetite and diet, in the setting of years of chronic diarrhea, hypothyroidism and macrocytic anemia. Her rapid weight loss resulted in a hospital admission where an extensive work-up failed to reveal signs of malignancy, paraneoplastic findings, autoimmune disorder or acute infection. However, electrolyte imbalances including low chloride and magnesium and a metabolic alkalosis prompted a diagnosis of Gitelman Syndrome. During this time period the patient suffered from progressive imbalance and proximal muscle weakness indicating a large fiber neuropathy. Her continued work up including an epidermal biopsy revealed the patient was also suffering from small fiber neuropathy as evidenced by a markedly low nerve fiber density. Up until this point her gastrointestinal symptoms were hypothesized to be related to chronic clostridium difficile gastroenteritis, however the diagnosis of SFN proved to be a revelation, as Gitelman Syndrome is a rare but known of SFN, which in turn has been well documented to cause enteric dysfunction, thus serving as source of this patient’s painful symptoms, weight loss, malnutrition and subsequent large fiber neuropathy.
Discussion: This complex case relates the extensive diagnostic work up of a patient with a rare etiology of small fiber neuropathy, with an unusual manifestation. While the treatment of fibromyalgia and pain due to SFN overlap substantially, the management of SFN focuses on treating the underlying condition, in this case Gitelman Syndrome. Were it not for the persistent efforts, multi-disciplinary approach and excellent intra-disciplinary communication, we may not have arrived at this elusive diagnosis.
