Diagnostic Challenges Associated with GLUT1 Deficiency: Phenotypic Variabilities and Evolving Clinical Features

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.

A Korean Family of Familial Medullary Thyroid Cancer with Cys618Ser RET Germline Mutation

Familial medullary thyroid carcinoma (FMTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. We screened members of a large Korean family that had a history of FMTC by genetic analyses, and propose a therapeutic approach for managing the disorder. We report a RET mutation in exon10, codon 618 that causes substitution of a cysteine by a serine in the cysteine-rich domain of the RET receptor in a three-generation FMTC family composed of 30 members with 11 carriers. Nine of the gene carriers were clinically affected. The FMTC with cysteine RET mutations found in the Korean population is consistent with the clinical pattern reported worldwide; to date there have been no ethnic differences identified for FMTC. Our results suggest that this genetic profile might be associated with usually aggressive clinical course with regional lymph node metastasis but late onset of MTC.

Prognostic Value of the Preoperative CEA, CA15-3 and TPS Serum Levels in Patients with Breast Cancer

PURPOSE: Tumor markers are often used to monitor the response to therapy and to detect recurrences in patients with resected breast cancer. Here we evaluated the prognostic value of the preoperative serum concentrations of tumor markers in patients with breast cancer. METHODS: The preoperative serum concentrations of tumor markers (CEA, CA15-3 and TPS) were measured in 670 patients who were treated via potentially curative surgical resection for breast cancer from 2001 to 2004. We investigated the association of the serum concentrations of tumor markers with the disease-free survival and overall survival at the time of the primary diagnosis in relation to the established prognostic factors such as tumor size, lymph node status, hormonal receptor status, age and menopausal status. RESULTS: The established prognostic factors and the elevated preoperative serum tumor marker values were correlated with disease-free survival (CEA: P=0.014, CA15-3: P=0.002 and TPS: P<0.001) and overall survival (CEA: P=0.045, CA15-3: P=0.002 and TPS: P<0.001) on univariate analysis. On multivariate analysis, tumor size, lymph node status, hormone receptor status and TPS (P=0.03) were independent prognostic factors for recurrence and the lymph node status, hormone receptor status and TPS serum level (P<0.001) were independent prognostic factors for overall survival. CONCLUSION: The preoperative serum concentrations of tumor makers (CEA, CA15-3 and TPS) are strong independent prognostic factors for recurrence and survival in patients with breast cancer. The tests for the preoperativeserum concentrations of tumor markers have convenient and reproducible advantages while the others require tumor tissue. Patients with elevated preoperative serum tumor marker values need appropriate adjuvant therapy, careful monitoring and detection of recurrences during the follow-up period.