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Riboflavin transporter deficiency (RTD) (MIM #614707) is a neurogenetic disorder with its most common manifestations including sensorineural hearing loss, peripheral neuropathy, respiratory insufficiency, and bulbar palsy. Here, we present a 2-year-old boy whose initial presentation was severe macrocytic anemia necessitating multiple blood transfusions and intermittent neutropenia; he subsequently developed ataxia and dysarthria. Trio-exome sequencing detected compound heterozygous variants in SLC52A2 that were classified as pathogenic and a variant of uncertain significance. Bone marrow evaluation demonstrated megaloblastic changes. Notably, his anemia and neutropenia resolved after treatment with oral riboflavin, thus expanding the clinical phenotype of this disorder. We reiterate the importance of starting riboflavin supplementation in a young child who presents with macrocytic anemia and neurological features while awaiting biochemical and genetic work up. We detected multiple biochemical abnormalities with the help of untargeted metabolomics analysis associated with abnormal flavin adenine nucleotide function which normalized after treatment, emphasizing the reversible pathomechanisms involved in this disorder. The utility of untargeted metabolomics analysis to monitor the effects of riboflavin supplementation in RTD has not been previously reported.

Pearls cRelapse of anti-NMDA receptor (NMDAR) encephalitis should be considered in all patients with history of anti-NMDAR encephalitis presenting with new acute-onset encephalopathy or psychosis. c CSF antibody diagnostic testing is sensitive and specific for the initial diagnosis of anti-NMDAR encephalitis.c Although CSF antibody titers correlate more closely with disease severity than serum titers, the utility of comparison to baseline or remission titers in order to diagnose relapse is still under investigation. Oy-sters cLong-term clinical monitoring after anti-NMDAR antibody encephalitis is necessary for appropriate diagnosis and treatment of relapse, as the interpretation of elevated antibody titers without clinical change is of unclear significance. Although current confirmed cases suggest a median of 2 years between the initial episode and first relapse, increasing reports suggest that longer periods of monitoring may be needed.A 33-year-old right-handed woman with a history of anti-NMDA receptor (NMDAR) encephalitis presented with a 1-day history of vomiting and bizarre behavior in the context of recent cannabis and synthetic cannabinoid ingestion. She had been diagnosed 7 years earlier with anti-NMDAR encephalitis complicated by refractory epilepsy and treated with a 5-day course of IV methylprednisolone (IVMP), a 5-day course of IV immunoglobulin (IVIg), and 2 doses of rituximab. Her prior admission was characterized by a prolonged stay with slow clinical improvement ultimately resulting in complete resolution and no longer requiring antiepileptic medications. Anti-NMDAR immunoglobulin G (IgG) antibody was positive (titers not recorded) and CT chest/abdomen/pelvis, MRI pelvis, and transvaginal ultrasound were negative for malignancy. She was last seen at our institution 1.5 years prior to the current presentation without sequelae.On current presentation, the patient was initially hemodynamically stable with intact orientation and attention. Neurologic examination was significant only for diffuse hyperreflexia. Within an hour, she became acutely obtunded and developed orofacial dyskinesias, sensory anesthesia, tachycardia, and acral hyperhidrosis with no improvement over the next 3 days. Urine toxicology was positive for cannabinoids but basic laboratory studies (complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B 12 , folic acid, HIV, urinalysis) were unremarkable. On further workup, MRI brain with and without contrast was normal and showed neither T2 fluid-attenuated inversion recovery (FLAIR) changes nor enhancement. EEG showed diffuse slowing with no posterior dominant rhythm or epileptiform discharges. CSF showed 40 white blood cells (normal 0-5) with 90% lymphocytes and 10% monocytes, glucose 61 mg/dL (normal 50-80), protein 24.2 mg/dL (normal 15-45), and 0 red blood cells. CSF flow cytometry was negative for aberrant T-/B-cell populations, and cytology was negative for malignant cells. Routine CSF studies were negative for gram stain and culture, herpes simplex v...

Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD; MIM #616084) is an autosomal recessive disorder of mitochondrial and cytosolic tRNA processing caused by pathogenic, biallelic variants in TRNT1. Other features of this disorder include central nervous system, renal, cardiac, ophthalmological features, and sensorineural hearing impairment. SIFD was first described in 2013 and to date, it has been reported in 46 patients. Herein, we review the literature and describe two siblings with SIFD and note the novel phenotype of hypoglycemia in the context of growth hormone (GH) deficiency. GH deficiency without hypoglycemia has previously been reported in three patients with SIFD, but GH deficiency had not been firmly ascribed to SIFD. We propose to expand the phenotype to include GH deficiency, hypoglycemia, and previously unreported dysmorphic features. Furthermore, we highlight the intrafamilial variability of the disease by the discordance of our patients' clinical phenotypes and biochemical profiles measured by untargeted metabolomics analysis. Several metabolomic abnormalities were observed in both patients, and these may represent a potential biochemical signature for SIFD.