Clinical Reasoning: A 51-Year-Old Woman With Diplopia and Headache.

A 51-year-old woman presented with a pressure-like headache behind her right eye and horizontal diplopia. On examination, she was unable to abduct or adduct the right eye but had intact vertical eye movements. Her deficits could not be overcome using the oculocephalic reflex. Imaging initially was interpreted as optic neuritis, but on careful review with radiology, a diffuse enhancing hyperintense signal within the orbital apex confirmed an orbital infiltrate. The focus of this case study is to review the localization approach for diplopia and build a differential diagnosis for orbital processes. Another key point is the importance of relying on the physical examination as the guide to a patient's management rather than imaging findings, which can often be misleading.

Novel mutations in the mitochondrial complex I assembly gene NDUFAF5 reveal heterogeneous phenotypes.

Primary mitochondrial complex I deficiency is the most common defect of the mitochondrial respiratory chain. It is caused by defects in structural components and assembly factors of this large protein complex. Mutations in the assembly factor NDUFAF5 are rare, with only five families reported to date. This study provides clinical, biochemical, molecular and functional data for four unrelated additional families, and three novel pathogenic variants. Three cases presented in infancy with lactic acidosis and classic Leigh syndrome. One patient, however, has a milder phenotype, with symptoms starting at 27 months and a protracted clinical course with improvement and relapsing episodes. She is homozygous for a previously reported mutation, p.Met279Arg and alive at 19 years with mild neurological involvement, normal lactate but abnormal urine organic acids. We found the same mutation in one of our severely affected patients in compound heterozygosity with a novel p.Lys52Thr mutation. Both patients with p.Met279Arg are of Taiwanese descent and had severe hyponatremia. Our third and fourth patients, both Caucasian, shared a common, newly described, missense mutation p.Lys109Asn which we show induces skipping of exon 3. Both Caucasian patients were compound heterozygotes, one with a previously reported Ashkenazi founder mutation while the other was negative for additional exonic variants. Whole genome sequencing followed by RNA studies revealed a novel deep intronic variant at position c.223-907A>C inducing an exonic splice enhancer. Our report adds significant new information to the mutational spectrum of NDUFAF5, further delineating the phenotypic heterogeneity of this mitochondrial defect.

Delayed osteomyelitis resulting from an extension injury of the cervical spine: case report.

Osteomyelitis of the cervical spine is an exceedingly rare lesion in pediatric practice and is caused by a variety of mechanisms. The authors present a case in which cervical osteomyelitis presented in a delayed manner after the patient experienced a stable cervical extension injury at the C4-5 level. On review of the original images, the authors noted a likely perforation in the retropharyngeal space. This case highlights the risk of retropharyngeal injury in cervical trauma, with the seldom-seen complication of osteomyelitis as a result.

Infantile Serine Biosynthesis Defect Due to Phosphoglycerate Dehydrogenase Deficiency: Variability in Phenotype and Treatment Response, Novel Mutations, and Diagnostic Challenges.

Serine biosynthesis defects can present in a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal disease with multiple congenital anomalies at the severe end, to an infantile disease with severe psychomotor retardation and seizures as an intermediate phenotype, to a childhood disease with intellectual disability at the mild end. In this report we present 6 individuals from 3 families with infantile phosphoglycerate dehydrogenase (PGDH) deficiency who presented with psychomotor delay, growth failure, microcephaly, and spasticity. The phenotype was variable with absence of seizures in 2 sisters in family 1 and 1 infant in family 2 and seizures with pronounced happy affect in 3 sisters in family 3. The initiation of serine treatment had pronounced effect on seizures and spasticity in the sisters in family 3, but minimal developmental effects on the children in families 1 and 2. With such phenotypic variability, the diagnosis of PGDH deficiency can be challenging.