Two male siblings from a consanguineous union presented in early infancy with marked truncal hypotonia, a general paucity of movement, extrapyramidal signs and cognitive delay. By mid-childhood they had made little developmental progress and remained severely hypotonic and bradykinetic. They developed epilepsy and had problems with autonomic dysfunction and oculogyric crises. They had a number of orthopaedic problems secondary to their hypotonia. Cerebrospinal fluid (CSF) neurotransmitters were initially normal, apart from mildly elevated 5-hydroxyindolacetic acid, and the children did not respond favourably to a trial of levodopa-carbidopa. The youngest died from respiratory complications at 10 years of age. Repeat CSF neurotransmitters in the older sibling at eight years of age showed slightly low homovanillic acid and 5-hydroxyindoleacetic acid levels. Whole-exome sequencing revealed a novel mutation homozygous in both children in the monoamine transporter gene SLC18A2 (p.Pro237His), resulting in brain dopamine-serotonin vesicular transport disease. This is the second family to be described with a mutation in this gene. Treatment with the dopamine agonist pramipexole in the surviving child resulted in mild improvements in alertness, communication, and eye movements. This case supports the identification of the causal mutation in the original case, expands the clinical phenotype of brain dopamine-serotonin vesicular transport disease and confirms that pramipexole treatment may lead to symptomatic improvement in affected individuals.

PTSD due to acute cardiovascular events may be uniquely defined by enduring perceptions of somatic threat. We tested whether PTSD at 1 month post-acute coronary syndrome (ACS) indeed required both high peritraumatic threat during the ACS and ongoing cardiac threat perceptions. We assessed peritraumatic threat during emergency department (ED) enrollment of 284 patients with a provisional ACS diagnosis, and cardiac threat perceptions and PTSD symptoms 1 month post-discharge. In a multiple regression model with adjustment for important covariates, ED threat perceptions were associated with higher 1-month PTSD symptoms only among those with high levels of ongoing cardiac threat.

Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ and the siblings were subsequently established on a therapeutic dose of CoQ with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

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We examined whether beta blocker administration in the emergency department (ED) during evaluation for suspected acute coronary syndrome (ACS) was associated with posttraumatic stress disorder (PTSD) symptoms 1 month later. Participants (N = 350) were enrolled in the Reactions to Acute Care and Hospitalization (REACH) study, an ongoing observational cohort study of ED predictors of medical and psychological outcomes after evaluation for suspected ACS. Beta blockade during evaluation in the ED was extracted from medical records, and PTSD symptoms in response to the experience of suspected ACS were assessed 1 month later via telephone. Beta blockade in the ED was associated with lower PTSD symptoms 1 month later (b = −2.80, β = −.09, p = .045), after adjustment for demographics, preexisting psychological and medical covariates, and participants’ distress during ED evaluation. Despite small effects, findings suggest that beta blockade during ED evaluation for suspected ACS—a time period relevant to fear consolidation of the memory of this potentially life-threatening event—may have protective effects for later psychological health.