The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses.

Purpose: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet many remain without a molecular diagnosis. The Australian Genomics Mitochondrial Flagship, comprising clinicians, diagnostic, and research scientists, conducted a prospective national study to identify the diagnostic utility of singleton genomic sequencing using blood samples.

Methods: A total of 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mitochondrial DNA (mtDNA) sequencing or genome sequencing.

Real world outcomes and implementation pathways of exome sequencing in an adult genetic department.

Purpose: This study aimed to correlate the indications and diagnostic yield of exome sequencing (ES) in adult patients across various clinical settings. The secondary aim was to examine the clinical utility of ES in adult patients.

Methods: Data on demographics, clinical indications, results, management changes, and cascade testing were collected for 250 consecutive patients who underwent ES through an adult genetics department between 2016 and 2021.

Phenotypic Spectrum of Seizure Disorders in MBD5-Associated Neurodevelopmental Disorder.

Objective: To describe the phenotypic spectrum in patients with MBD5-associated neurodevelopmental disorder (MAND) and seizures; features of MAND include intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, and dysmorphic features including short stature and microcephaly, sleep disturbance, and ataxia.

Methods: We performed phenotyping on patients with deletions, duplications, or point mutations and a history of seizures.

Results: Twenty-three patients with MAND and seizures were included.

The severe epilepsy syndromes of infancy: A population-based study.

Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes.

Methods: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes.

The effect of improved dietary control on cognitive and psychiatric functioning in adults with phenylketonuria: the ReDAPT study.

Background: Phenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase. Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals who discontinue dietary control subsequently suffer symptoms of anxiety, depression and disturbances to cognition.

OCD symptoms in succinic semialdehyde dehydrogenase (SSADH) deficiency: a case report.

Background: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder resulting in a heterogeneous clinical phenotype. Adolescent and adult patients with SSADH deficiency may present with OCD symptoms. There is minimal literature regarding the pathological basis of OCD symptoms and their management amongst SSADH deficiency patients.

Psychiatric and Cognitive Aspects of Phenylketonuria: The Limitations of Diet and Promise of New Treatments.

Phenylketonuria (PKU) is a recessive disorder of phenylalanine metabolism due to mutations in the gene for phenylalanine hydroxylase (PAH). Reduced PAH activity results in significant hyperphenylalaninemia, which leads to alterations in cerebral myelin and protein synthesis, as well as reduced levels of serotonin, dopamine, and noradrenaline in the brain. When untreated, brain development is grossly disrupted and significant intellectual impairment and behavioral disturbance occur.