Novel homozygous mutation in the FBXL4 gene is associated with mitochondria DNA depletion syndrome-13.

BACKGROUND: Mitochondrial DNA depletion syndrome-13 (MTDPS13) is caused by mutations in FBXL4 (F-box and leucine-rich repeat protein 4), a nuclear gene encoding an F-box protein that plays a role in maintaining mtDNA integrity and stability. METHODS: We identified a novel homozygous FBXL4 gene mutation, c.993dupA (p.L332Tfs*3), in a 1-year-old girl of Han Chinese descent. We performed three-dimensional protein structural analysis and targeted mtDNA next-generation sequencing. We analysed FBXL4 expression and mitochondrial DNA level, and reviewed mutations reported in FBXL4-related literature. RESULTS: This mutation resulted in premature termination of translation and loss of 288 amino acids from C-terminus. A three-dimensional structural analysis revealed that conserved LRR domains were lost in mutant FBXL4 protein, which likely affected its ability to form protein-protein interactions. There were no differences in FBXL4 mRNA expression levels between the patient and her parents. There were no mtDNA mutations in either the patient or her parents. However, ND1/GAPDH ratio in lymphocytes and urine, which represents mtDNA/nuclear DNA ratio, showed that the number of mitochondrial genomes was significantly lower in the patient than in her parents or wild-type subjects. CONCLUSION: Homozygous FBXL4 gene mutation, c.993dupA, can cause mitochondrial dysfunction, and LRR region is especially important for FBXL4 protein function.

Bumbling, Stumbling, Fumbling: Weakness, Steppage Gait, and Facial Droop in a 3-Year-Old Male.

A previously healthy, unimmunized, 3-year-old Caucasian boy presented to the emergency department with right-sided facial droop, clumsiness, and intermittent bilateral hip pain. Two weeks ago, he had 24 hours of self-resolving rhinorrhea and fever. Examination was significant for right facial nerve palsy, lower extremity pain, areflexia of his right lower extremity, and diminished reflexes of his left lower extremity. He was admitted for urgent magnetic resonance imaging of the brain. Cerebrospinal fluid (CSF) protein was 85 mg/dL with elevated albumin and immunoglobulin, and CSF white blood cell was 3 cells/mm3. Serum Mycoplasma immunoglobulin (Ig) M and IgG were elevated. There was concern for Guillain-Barré syndrome (GBS). He was started on intravenous IG (IVIG) and was treated for presumed Mycoplasma infection. Weakness and gait disturbances in a child can present the clinician with a diagnostic challenge. Gait disturbance may indicate a neurological lesion anywhere from the central nervous system to the peripheral nerves, neuromuscular junction, or muscle. In the present case, the combination of peripheral facial palsy, presumed neuropathic pain, gait difficulties, and areflexia in the setting of an antecedent respiratory illness were suggestive of GBS. The cornerstone treatments involve hospitalization to facilitate continuous monitoring for serious sequelae, such as acute respiratory failure and cardiac dysrhythmia, followed by immunotherapy with IVIG or plasma exchange. Gait disturbance and weakness in a child is a diagnostic challenge. GBS is the most common cause of acute paralysis in the Western world and should remain high on the clinician's differential diagnosis. However, patients with GBS may also present nonclassically with extremity pain and cranial nerve palsies.

Sleep Disorders in Childhood Neurological Diseases.

Sleep problems are frequently addressed as a primary or secondary concern during the visit to the pediatric neurology clinic. Sleep disorders can mimic other neurologic diseases (e.g., epilepsy and movement disorders), and this adds challenges to the diagnostic process. Sleep disorders can significantly affect the quality of life and functionality of children in general and those with comorbid neurological diseases in particular. Understanding the pathophysiology of sleep disorders, recognizing the implications of sleep disorder in children with neurologic diseases and behavioral difficulties, and early intervention continue to evolve resulting in better neurocognitive outcomes.

Diagnosis and management of childhood epilepsy.

Epilepsy is a relatively common neurologic disorder in children that has important implications for development, parents, and society. Making the correct diagnosis starts with an accurate and complete history that consequently leads to a directed diagnostic workup. This article outlines a diagnostic and management approach to pediatric seizures and epilepsy syndromes. Making the correct diagnosis of epilepsy or nonepileptic imitators allows the practitioner to prescribe appropriate therapy. Initial management for typical epileptic syndromes and seizures and potential adverse effects are discussed. Alternative treatment options for pharmacologically resistant patients such as ketogenic diet, vagal nerve stimulation, and surgery are also discussed. While most children favorably respond to antiepileptic medications, early identification of medication failure is important to ensure optimal neurodevelopment.

The role of drains in lumbar spine fusion.

OBJECTIVE: To study the role of drains in lumbar spine fusions. METHODS: The charts of 402 patients who underwent lumbar decompression and fusion (LDF) were retrospectively reviewed. Patients were classified per International Classification of Diseases, 9th Edition (ICD-9) procedure code as 81.07 (lateral fusion, 74.9%) and 81.08 (posterior fusion, 25.1%). The investigators studied the prevalence of drain use in lumbar fusion procedures and the impact of drain use on postoperative fever, wound infection, posthemorrhagic anemia, blood transfusion, and hospital cost. RESULTS: No significant differences in wound infection rates were noted between patients with and without drains (3.5% vs 2.6%, P = 0.627). The difference in postoperative fever rates between patients with and without drains (63.2% vs 52.6%, P = 0.05) was of borderline significance. Posthemorrhagic anemia was statistically more common in patients with drains (23.5% vs 7.7%, P = 0.000). Allogeneic blood transfusion was also statistically more common in the drained group (23.9% vs 6.8%, P = 0.000). Postoperative hemoglobin levels were lower in patients with drains who underwent one-level (9.5 g/dL vs 11.3 g/dL) or two-level (9.3 g/dL vs 10.2 g/dL) spine fusions. In this series in which drains were liberally used, no patient had to return to the operating room because of postoperative hematoma. An increased rate of allogeneic blood transfusion was noticed with posthemorrhagic anemia and drain use. The rate of allogeneic blood transfusion increased from 5.6% in patients without drains or posthemorrhagic anemia to 38.8% in patients with drains and posthemorrhagic anemia as a secondary diagnosis. The use of drains was associated with statistically insignificant increases in length of stay and cost in posterior procedures. Drain use was associated with shorter length of stay and hospital charges in lateral fusions of three or more levels. CONCLUSIONS: Drain use did not increase the risk of wound infection in patients undergoing LDF, but it had some impact on the prevalence of postoperative fever. Drain use was significantly associated with posthemorrhagic anemia and allogeneic blood transfusion. Drain use did not have a significant economic impact on hospital length of stay and charges except in lateral procedures involving three or more levels.

De novo spine surgery as a predictor of additional spine surgery at the same or distant spine regions.

INTRODUCTION: Degenerative spine disorders are steadily increasing parallel to the aging of the population with considerable impact on cost and productivity. In this paper we study the prevalence and risk factors for multiple spine surgery and its impact on cost. METHODS: Data on 1,153 spine surgery inpatients operated between October 2005 and September 2008 (index spine surgery) in regard to the number of previous spine surgeries and location of surgeries (cervical or lumbar) were retrospectively collected. Additionally, prospective follow-up over a period of 2-5 years was conducted. RESULTS: Retrospectively, 365 (31.7%) patients were recurrent spine surgery patients while 788 (68.3%) were de novo spine surgery patients.Nearly half of those with previous spine surgery (51.5%) were on different regions of the spine. There were no significant differences in length of stay or hospital charges except in lumbar decompression and fusion (LDF) patients with multiple interventions on the same region of the spine. Significant differences (P<.05) in length of stay (5.4 days vs. 7.4 days) and hospital charges ($55,477 vs. $74,878) between LDF patients with one previous spine versus those with ≥3 previous spine surgeries on the same region were noted.Prospectively, the overall reoperation rate was 10.4%. The risk of additional spine surgery increased from 8.0% in patients with one previous spine surgery (index surgery) to 25.6% in patients with ≥4 previous spine surgeries on different regions of the spine (including index surgery).After excluding patients with previous spine surgeries on different regions of the spine, 17.2% of reoperated patients had additional spine surgery on a different spine region. The percentage of additional spine surgery on a distant spine region increased from 14.0% in patients with one spine surgery to 33.0% in patients with two spine surgeries on the same region. However, in patients with three or more spine surgeries on the same spine region there were no interventions on a distant spine region during the follow-up period. CONCLUSION: De novo spine surgery is associated with an increased incidence of additional spine surgery at the same or distant spine regions. Large prospective studies with extended follow-up periods and multifaceted cost-outcome analysis are needed to refine the appropriateness of spine surgery.