Improvement of neutropenia in 2 adolescent cases treated with empagliflozin for glycogen storage disease type Ib

Neutropenia and elevated concentrations of hepatic transaminases often lead to referrals from emergency or outpatient departments to relevant specialists to diagnose underlying inborn errors of metabolism. Glycogen storage disease type (GSD) Ib, a rare congenital disorder of glucose metabolism caused by the SLC37A4 gene mutations, shows various manifestations, including persistent neutropenia and elevated hepatic transaminases. Empagliflozin has demonstrated its efficacy in treating GSD Ib-associated neutropenia by reducing the entry of 1,5-anhydroglucitol-6-phosphate into the neutrophils. This article reports successful empagliflozin therapy for GSD Ib-related neutropenia in 2 Korean adolescents. Diagnosing GSD Ib is complex and usually initiated by a referral from emergency or outpatient departments when there is a high index of suspicion. Once diagnosed, empagliflozin shows promising outcomes in restoring counts and function of the neutrophils without severe adverse effects in children with GSD Ib, supporting it as a safe and effective therapeutic option for GSD Ib-associated neutropenia.

Clinical Usefulness of Simultaneous Electroencephalography and Functional Magnetic Resonance Imaging in Children With Focal Epilepsy

Background@#and Purpose The current study analyzed the interictal epileptiform discharge (IED)-related hemodynamic response and aimed to determine the clinical usefulness of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) in defining the epileptogenic zone (EZ) in children with focal epilepsy. @*Methods@#Patients with focal epilepsy showing IEDs on conventional EEG were evaluated using EEG-fMRI. Statistical analyses were performed using the times of spike as events modeled with multiple hemodynamic response functions. The area showing the most significant t-value for blood-oxygen-level-dependent (BOLD) changes was compared with the presumed EZ. Moreover, BOLD responses between -9 and +9 s around the spike times were analyzed to track the hemodynamic response patterns over time. @*Results@#Half (n=13) of 26 EEG-fMRI investigations of 19 patients were successful. Two patients showed 2 different types of spikes, resulting in 15 analyses. The maximum BOLD response was concordant with the EZ in 11 (73.3%) of the 15 analyses. In 10 (66.7%) analyses, the BOLD response localized the EZs more specifically. Focal BOLD responses in the EZs occurred before IEDs in 11 analyses and were often widespread after IEDs. Hemodynamic response patterns were consistent in the same epilepsy syndrome or when repeating the investigation in the same patients. @*Conclusions@#EEG-fMRI can provide additional information for localizing the EZ in children with focal epilepsy, and also reveal the pathogenesis of pediatric epilepsy by evaluating the patterns in the hemodynamic response across time windows of IEDs.

Two Korean siblings with autosomal recessive spinocerebellar ataxia 20 caused by homozygous variants in SNX14

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by lossof-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years.The younger sibling’s MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.

A Pediatric Case of AVPR2-related Nephrogenic Syndrome of Inappropriate Antidiuresis

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked genetic condition caused by a gain-of-function mutation of arginine vasopressin receptor 2 gene, AVPR2. We report the case of a male neonate diagnosed with NSIAD based on his DNA sequence of the AVPR2 gene and the clinical course. He demonstrated a complete correction of hyponatremia using oral urea. We suggest that (1) sequencing analysis of the AVPR2 gene ought to be done in newborns with prolonged euvolemic hyponatremia, hypo-osmolality, high urinary sodium and normal/low or undetectable AVP levels, and that (2) oral urea is a safe and effective treatment option in infants diagnosed with NSIAD until the patients are grown-up.

Reversible Metronidazole-induced Encephalopathy in a Patient with Acute Lymphoblastic Leukemia during Chemotherapy / 임상소아혈액종양

We describe our experience regarding metronidazole-induced encephalopathy in a patient with acute lymphoblastic leukemia during chemotherapy. A 17-year-old girl was admitted to our institution with complaints of abdominal pain and mucoid stools. She was diagnosed with acute lymphoblastic leukemia and had been undergoing intensified chemotherapy protocol. During the fifth week of interim maintenance-1 therapy, she developed a fever and complained of chills. On stool examination, stool occult blood was positive and Clostridium difficile toxin A/B test was positive. She was started on metronidazole treatment for possible Clostridium difficile infection and other inflammatory gastrointestinal diseases. Ten days later, the patient complained of dizziness and nausea. A brain MRI was performed to make a differential diagnosis of any chemotherapy- induced CNS complication such as necrotizing leukoencephalopathy. The brain MRI showed features of metronidazole-induced encephalopathy. Metronidazole was discontinued and symptoms started to subside four days after. A follow-up brain MRI performed at four weeks showed that lesions of the dentate nucleus had disappeared.

Reversible Metronidazole-induced Encephalopathy in a Patient with Acute Lymphoblastic Leukemia during Chemotherapy / 임상소아혈액종양

We describe our experience regarding metronidazole-induced encephalopathy in a patient with acute lymphoblastic leukemia during chemotherapy. A 17-year-old girl was admitted to our institution with complaints of abdominal pain and mucoid stools. She was diagnosed with acute lymphoblastic leukemia and had been undergoing intensified chemotherapy protocol. During the fifth week of interim maintenance-1 therapy, she developed a fever and complained of chills. On stool examination, stool occult blood was positive and Clostridium difficile toxin A/B test was positive. She was started on metronidazole treatment for possible Clostridium difficile infection and other inflammatory gastrointestinal diseases. Ten days later, the patient complained of dizziness and nausea. A brain MRI was performed to make a differential diagnosis of any chemotherapy- induced CNS complication such as necrotizing leukoencephalopathy. The brain MRI showed features of metronidazole-induced encephalopathy. Metronidazole was discontinued and symptoms started to subside four days after. A follow-up brain MRI performed at four weeks showed that lesions of the dentate nucleus had disappeared.