RESUMEN
EAST/SeSAME syndrome is a rare disease affecting the Central Nervous System (CNS), inner ear, and kidney. The syndrome is due to loss-of-function mutations in the KCNJ10 gene encoding the inward-rectifying potassium channel Kir4.1. EAST/SeSAME syndrome is mainly diagnosed during childhood with a tonic-clonic seizure being the usual first symptom. Due to a limited number of patients and recent identification of the disease, few data are available on the clinical progress of this disease in adulthood. In particular, neurologic and nephrological outcomes have not been reported. We present a case series of 4 adult patients harbouring homozygous missense mutation p.Ala167Val and homozygous frameshift mutations p.Asn232Glnfs*14 and p.Gly275Valfs*7. Effects of these mutations were predicted by in silico modelling and bioinformatic tools. Patients with truncating mutations were associated with more severe outcomes, both in tubulopathy severity and neurological symptomatology. Conversely, either missense or truncating mutations were correlated with similar severity of epilepsy, with a long free-of-event period up to 20 years old. No eGFR decline was documented. Modelling predicted that truncating mutations lead to complete Kir4.1 dysfunction. Finally, all patients had a mild increase in urinary protein excretion. Our study indicates that the prognosis of patients suffering from EAST/SeSAME syndrome is related to the severity of the mutation causing the disease. As predicted by in silico modelling, truncating mutations of KCNJ10 are associated with more severe disease, with recurrence of symptomatic hypokalemia and more severe neurological phenotype. The type of mutation should be considered for the therapy tailored to patients' phenotype.
RESUMEN
BACKGROUND: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. METHODS: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016-2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite "amyloid score" score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. RESULTS: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p < 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813-0.962; p < 0.001). CONCLUSIONS: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA.
RESUMEN
BACKGROUND: Although fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine. CASE PRESENTATION: A 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6-1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule). LITERATURE REVIEW: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases. DISCUSSION AND CONCLUSIONS: Our case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1-3 months if unstable, twice-yearly in stable patients).