A 65-year-old Caucasian lady was referred to our Ataxia Clinic because of a 6-year history of progressive unsteadiness and a 2-year history of slurred speech. Past medical history included arterial hypertension. The patient was a non-smoker was not consuming alcohol excessively. There was no family history of ataxia.
Neurological examination revealed prominent gaze-evoked nystagmus, heel to shin ataxia, gait ataxia, reduced reflexes and loss of vibration sensation in the legs.
Routine blood tests included full blood count, erythrocyte sedimentation rate, urea, creatinine, electrolytes, liver function tests, thyroid function tests, random glucose, Vitamin B12, folate, Vitamin E and folate, were all normal.
Extensive immunology screening included immunoglobulins and serum electrophoresis, antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) antibodies, GAD antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), thyroid peroxidase (TPO) antibodies, endomysium antibodies, transglutaminase antibodies and gliadin antibodies. From those, the IgA and IgM titer were low (IgA 0.63 g/L, normal values 0.8-4.0 and IgM 0.22 g/L, normal values 0.5-2.0), with no electrophoretic abnormality noted. C-ANCA antibodies were positive but PR3 antibodies were negative. Interestingly, the patient had the DQ8 human leukocyte antigen (HLA) serotype, which is commonly linked to autoimmune diseases, including coeliac disease.
The MRI of the brain was unremarkable for the patient's age, with no evidence of cerebellar atrophy in particular. However, the magnetic resonance spectroscopy (MRS) of the cerebellar vermis revealed a low N-acetyl aspartate (NAA) to Creatine (Cr) area ratio (NAA/Cr 0.95, normal values  > 1.0) (Fig. 1A). Low NAA/Cr ratio implies abnormal metabolic activity within the area of interest (voxel). It can be used as an indicator to cerebellar dysfunction. 
Sensory conduction studies of the right median, right ulnar, right radial and both sural nerves showed attenuated amplitudes, when the motor conduction studies of the right median, right ulnar and right peroneal nerves were within normal limits. The electrically elicited blink reflex was tested bilaterally and revealed an asymmetric involvement of the trigeminal/facial nerve pathways, suggesting a diagnosis of sensory ganglionopathy.
As the combination of cerebellar ataxia with sensory ganglionopathy can be seen as part of hereditary ataxias, including mitochondrial diseases, the patient was initially tested and was negative for the common genetic ataxias (Fridriech's ataxia, SCA1, SCA2, SCA3, SCA6 and SCA7). Subsequent further genetic testing using new generation sequencing was also negative and included the following genes; ABCB7, AFG3L2, APTX, ATM, ATP1A2, ATP1A3, ATP7B, C10orf2, CACNA1A, CACNB4, CYP2U1, CYP27A1, DDHD2, EEF2, FGF14, FTL, FXN, GBA, GBA2, IFRD1, ITPR1, KCNA1, KCNC3, KCND3, MTPAP, PDYN, PRKCG, PRRT2, SACS, SCN1A, SETX, SIL1, SLC16A2, SLC1A3, SLC2A1, SPG7, SPTBN2, TGM6, TTBK2, TTPA, VAMP1, ZFYVE26 (Additional file 1).
The patient has been followed-up on a 6 monthly basis and remained relatively stable. Thirty months after the initial presentation to our clinic repeat nerve conduction studies and repeat MRI and MRS were arranged. The nerve conduction studies showed further deterioration of the sensory ganglionopathy. The MRI of the brain showed is mild to moderate atrophy of the vermis (grade 2) and mild atrophy (grade 1) of the hemispheres (Fig. 2), when the MRS showed further deterioration of the NAA/Cr ratios of the cerebellum (Fig. 1B). 
In order to rule out mitochondrial disease the common mitochondrial mutations (MELAS, MERRF, NARP, POLG1) were tested and were negative and a muscle biopsy was arranged. Transmission electron microscopy of glutaraldehyde fixed muscle revealed the presence of endomysial amyloid. Histologically, no inflammation, necrosis, or inclusions were seen (Fig. 3). Urinalysis confirmed the presence of light chains. A bone marrow biopsy was performed confirming the diagnosis of light chain multiple myeloma. Scintigraphy showed predominantly cardiac involvement and the patient was referred for further treatment. 
Table 1 summarizes the nerve conduction tests and the MRS findings across the clinical course of the patient.