Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.

Paediatric Restrictive Cardiomyopathy - Diagnosis and Challenges: A report of two cases.

Restrictive cardiomyopathy is one of the rarest forms of cardiomyopathies in paediatric patients characterised by impaired myocardial relaxation or compliance with restricted ventricular filling, leading to a reduced diastolic volume with a preserved systolic function. We report 2 cases-a 5-year-old boy who presented with abdominal distension and palpitation with family history of similar complaints but no definite genetic diagnosis as yet and a 5-year-old girl who presented with chronic cough and shortness of breath. Both cases were diagnosed in a tertiary care hospital in Muscat, Oman, in 2019 and are managed supportively with regular outpatient follow-up. This is the first series of reported cases of paediatric restrictive cardiomyopathy from Oman.

Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India.

People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0 to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12, and there was no change in plasma folate concentration in any of the groups. Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from 2 to zero. There was no change in vibration sensory threshold during the period of the study. High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks. People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.

Increasing maternal parity predicts neonatal adiposity: Pune Maternal Nutrition Study.

OBJECTIVE: This study was undertaken to study the effect of parity on maternal and neonatal characteristics. STUDY DESIGN: Maternal anthropometry, diet, micronutrient status, biochemistry, and physical activity were measured during pregnancy and detailed neonatal size recorded in 770 pregnancies in rural Maharashtra, India. RESULTS: Increasing parity was associated with larger offspring birth weight, skinfold thicknesses, and abdominal circumference, but not head circumference and length. Compared with primiparous women, multiparous women were older, less adipose, and more physically active but had similar education, socioeconomic status, nutritional intake, and weight gain during pregnancy. They had lower circulating concentrations of hemoglobin, albumin, ferritin, glucose, and insulin and lower total leucocyte counts at 18 and 28 weeks' gestation. There was no difference in their husbands' body size. The relationship between maternal parity and neonatal weight and adiposity was significant independent of the difference in maternal characteristics. CONCLUSION: Increasing maternal parity predicts increasing adiposity in the newborn infant. This may result from maternal nutritional, cardiovascular, or immunologic factors.