Blood samples for ammonia analysis do not require transport to the laboratory on ice: a study of ammonia stability and cause of ammonia increase in samples from patients with hyperammonaemia.

Objectives: Prompt recognition of hyperammonaemia can avoid severe consequences of delayed treatment. Strict sample transport requirements present barriers to requesting and, if not achieved, rejection by the laboratory. Evidence is sparse on ammonia stability from studies using modern techniques or based in clinical settings.

Acceptability of plasma ammonia results when samples are not transported and processed under ideal conditions.

Background: It is recommended that samples for plasma ammonia analysis are kept chilled and processed promptly as metabolism causes falsely elevated results. Rejection of unsuitable samples can cause delayed diagnosis and treatment of hyperammonaemia with potentially serious clinical consequences. The Metabolic Biochemistry Network (MetBioNet) hyperammonaemia guideline recommends analysis of samples not collected under ideal conditions and reporting with appropriate comments.

Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach.

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an "Other disorder suspected" (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020.

Broadening the Spectrum of Phenotype: Primary Carnitine Deficiency Presenting with Focal Myoclonus.

Primary carnitine deficiency (PCD) is caused by pathogenic variants of the gene, which encodes a transmembrane protein that functions as a high affinity carnitine transporter. Carnitine is essential for the transport of acyl-CoA, produced from fatty acids, into the mitochondria where they are oxidised to produce energy. We present the case history of an 8-year-old boy who presented with fever, lethargy, focal rhythmic (3 Hz) left wrist twitching, and severe encephalopathy.

Recurrent hyperammonaemia in a patient with carbonic anhydrase VA deficiency.

Carbonic anhydrase VA deficiency is a recently described inherited cause of paediatric hyperammonaemia. Most published cases describe patients with only one episode of hyperammonaemia whilst others report patients who had up to three metabolic crises with the first invariably being the most severe. We describe a patient with carbonic anhydrase VA deficiency who experienced 7 hyperammonemic episodes over a 3-year period, up to age 5 years 9 months.

Correction: A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965.

Since the publication of this paper the authors noticed an error in the listed authors, where Alexandros Siskos was listed as Alexandros Sitkos. This has now been corrected.

A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965.

A 47-year-old man with metastatic melanoma presented with refractory hyperlactaemic acidosis following the first dose of the mono-carboxylase transporter 1 inhibitor AZD3965 within a "first time in man" clinical trial. The mechanism of the agent and the temporal relationship suggested that this event was potentially drug related and recruitment was suspended. However, urinary metabolomics showed extensive abnormalities even prior to drug administration, leading to investigations for an underlying metabolic disorder.

Ketoacidosis in Duchenne muscular dystrophy: A report on 4 cases.

The longer survival in Duchenne dystrophy can be associated with previously unrecognised medical issues, in particular cardiac and nutritional problems, which provide new challenges in the management of these patients. We describe a series of patients who have DMD presenting with severe acid base abnormalities due to ketoacidosis. The cases described all developed the abnormalities in the context of decreased dietary intake.

Cardiolipin fingerprinting of leukocytes by MALDI-TOF/MS as a screening tool for Barth syndrome.

Barth syndrome (BTHS), an X-linked disease associated with cardioskeletal myopathy, neutropenia, and organic aciduria, is characterized by abnormalities of card-iolipin (CL) species in mitochondria. Diagnosis of the disease is often compromised by lack of rapid and widely available diagnostic laboratory tests. The present study describes a new method for BTHS screening based on MALDI-TOF/MS analysis of leukocyte lipids.

Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible ameliorated phenotype.

Barth syndrome (BTHS) is an X-linked disorder characterised by cardiac and skeletal myopathy, growth delay, neutropenia and 3-methylglutaconic aciduria (3-MGCA). Patients have TAZ gene mutations which affect metabolism of cardiolipin, resulting in low tetralinoleoyl cardiolipin (CL(4)), an increase in its precursor, monolysocardiolipin (MLCL), and an increased MLCL/CL(4) ratio. During development of a diagnostic service for BTHS, leukocyte CL(4) was measured in 156 controls and 34 patients with genetically confirmed BTHS.

Barth syndrome.

First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history.

Diagnosis of Barth syndrome using a novel LC-MS/MS method for leukocyte cardiolipin analysis.

Barth syndrome (BTHS) is an X-linked disorder characterised by cardiomyopathy, skeletal myopathy, growth retardation, neutropenia and 3-methylglutaconic aciduria. It is caused by mutations in the TAZ gene which codes for tafazzin, a protein with acyl transferase activity involved in synthesis of cardiolipin. Monolysocardiolipin (MLCL) is an intermediate in this process.

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

Background: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown.

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items.

Increased HVA detected on organic acid analysis in a patient with Costello syndrome.

Urine organic acid analysis is routinely performed to investigate inborn errors of metabolism; however, interpretation can be difficult owing to the detection of compounds derived from other disease states or from nonpathological causes. We describe the finding of elevated homovanillc acid (HVA) on urine organic acid analysis which was not associated with medication or a neuroendocrine tumour but with Costello syndrome.

The influence of genetic and environmental factors on plasma homocysteine concentrations in a population at high risk for coronary artery disease.

Background: Elevated plasma total homocysteine (tHcy) predisposes to vascular disease and results from interactions between genetic and nutritional factors. MTHFR C(677)T increases tHcy in association with low folate. CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C(677)T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease.

Developing a Parkinson's Disease service.

People with Parkinson's Disease need information and support if they are to maintain an independent lifestyle. The establishment of a dedicated team in Northumbria for these patients is helping them and their carers to become involved in their care by offering education, counselling and information about medication.

Identification of motor and nonmotor wearing-off in Parkinson's disease: comparison of a patient questionnaire versus a clinician assessment.

This study compares the sensitivity of a Patient Questionnaire versus information gathered by clinicians at a routine clinic visit in recognizing symptoms of wearing-off in early Parkinson's disease (PD). This Patient Questionnaire, containing 32 items representing a wide spectrum of motor and nonmotor wearing-off symptoms, was administered to subjects attending two PD clinics. The Patient Questionnaire results were compared to the information gathered by the clinician from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36 and from a specific Clinical Assessment Question regarding loss of medication efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications, morning akinesia, other dopaminergic side effects, or none of the above.

Practical considerations in the use of apomorphine injectable.

This manuscript provides a practical summary of guidelines for institution of apomorphine subcutaneous injectable therapy, including patient education, pre-treatment issues, dosage titration and side-effect care. The timing of each injection is crucial if an impending "off" period is to be averted. Patients need to be aware of symptoms of an approaching "off" period, and the injection should be administered at the onset or ideally, in anticipation of an "off" episode.