Journal of clinical and diagnostic research

Neonatal Encephalopathy Associated with a Homozygous ACAD9 Variant of Mitochondrial Complex I Deficiency: A Case Report

Acyl-CoA dehydrogenase 9 (ACAD9)-related mitochondrial disease is an unusual, autosomal recessive disorder with impaired function of complex I of the mitochondrial respiratory-chain and can manifest as severe neonatal encephalopathy. The authors report a male neonate that was born at 37+1 weeks, following elective caesarean section due to previous caesarean delivery and polyhydramnios. At birth, he had poor respiratory effort, generalised hypotonia and apnoea requiring mechanical ventilation. Consanguinity and unexplained multiple neonatal deaths in the family raised a suspicion for an inherited metabolic disorder. The baby went on to have persistent hyperlactataemia, hyperammonaemia, recurrent apnoea and refractory seizures. Infectious investigations were negative and tandem mass spectrometry did not indicate the presence of classical urea-cycle disorders or organic acidemia. Lactate level in the Cerebrospinal Fluid (CSF) was high (more than 15 mg/dL). Brain Magnetic Resonance Imaging (MRI) showed diffusion restriction in the left frontal and parietal lobes, caudate nucleus and centrum semiovale in a non Arterial distribution, which were consistent with metabolic stroke-like lesions. Magnetic Resonance Spectroscopy (MRS) was supportive of Metabolic Brain Injury (MBI). Whole exome sequencing revealed a homozygous ACAD9 c.793A>G (p.Ile265Val) variant which was identified as a variant of uncertain significance. Treatment consisted of riboflavin, thiamine, pyridoxine, L-carnitine, coenzyme Q10, ammonia scavenging and antiepileptic therapy. Lactate and ammonia improved somewhat but neurological deterioration persisted, characterised by refractory seizures and progressive encephalopathy. The baby became very sick with multiorgan dysfunction and scuccumbed to death during 5th week of life. The lesson to be learned from the present case is that mitochondrial respiratory-chain disorders should be a component of the differential diagnosis in neonates who have unexplained encephalopathy, lactic acidosis, hyperammonaemia and metabolic stroke-like lesions, especially when consanguinity and recurrent unexplained neonatal deaths are present. It also highlights the need to consider segregation and functional studies in the interpretation of variants of unknown significance in ACAD9.

Invasive Shigella flexneri Bacteraemia in an Immunocompetent Child: A Rare Case Report

Shigella flexneri is a common cause of bacillary dysentery in children, especially in developing countries. However, bacteraemia due to Shigella species is rare, especially in immunocompetent and well-nourished children. A five-month-old male child presented with a 4-day history of high-grade fever and multiple episodes of watery diarrhoea, accompanied by abdominal pain for two days. On examination, the child showed signs of moderate dehydration but remained haemodynamically stable. Laboratory investigations revealed elevated inflammatory markers. Blood cultures grew non-lactose fermenting Gram-negative bacilli, which were identified as Shigella flexneri using an automated system. The isolate was susceptible to ceftriaxone, cefepime, cotrimoxazole, and azithromycin, but resistant to fluoroquinolones. The patient was treated with appropriate supportive care and intravenous ceftriaxone antibiotics that lead to gradual clinical improvement and successful recovery. Clinicians should consider Shigella bacteraemia in paediatric patients presenting with severe febrile diarrhoea. Timely blood culture and appropriate antimicrobial management are crucial for favourable prognosis, even in atypical presentations without known risk factors.

Disseminated Escherichia coli Sepsis with Multiple Visceral and Soft-tissue Abscesses as the Presenting Manifestation of Classic Galactosaemia in a Young Infant: A Case Report

Chirag Deora, Manish Tiwari

Classic galactosaemia, caused by deficient Galactose-1-Phosphate Uridyltransferase (GALT) activity, predisposes young infants to life-threatening Escherichia coli sepsis through galactose-metabolite-mediated immune dysfunction. A two-month-old breastfed male infant presenting with high-grade fever, poor feeding, and progressive swellings over the scalp, right thigh, and right axilla. Sepsis workup revealed leucocytosis, markedly elevated C-Reactive Protein (CRP), elevated hepatic transaminases, and E. coli bacteraemia. Contrast-Enhanced Computed Tomography (CECT) demonstrated multiple abscesses in the liver, spleen, and rectus abdominis muscle. Standard immunodeficiency evaluation was unremarkable. Urine reducing substances were positive for a non-glucose reducing sugar. Next-generation sequencing identified a heterozygous pathogenic GALT c.563A>G (p.Gln188Arg; Q188R) variant; the biochemical and clinical constellation was consistent with classic galactosaemia, with a likely second pathogenic allele not detected by the panel used. Immediate lactose elimination, prolonged intravenous meropenem, and image-guided abscess drainage resulted in complete clinical and radiological resolution. At 3-month post-discharge follow-up, the infant was thriving with no abscess recurrence. E. Coli sepsis with multifocal abscesses should prompt metabolic evaluation for galactosaemia when immunodeficiency workup is unremarkable. Early recognition through bedside urine reducing substance testing, immediate elimination of dietary lactose and aggressive source control are pivotal to achieving a favourable outcome in this potentially fatal but treatable disorder.

Clinical Profile, Risk Factors and Outcomes of Neonates with Respiratory Distress at a Rural Tertiary Care Setting, Tamil Nadu, India: A Prospective Cohort Study

Nalayini Jeyasankar, Karthik Narayan, Anusha Chelladurai, Sarojini Jeyasankar

Introduction: Neonatal Respiratory Distress (RD) is one of the leading causes of Neonatal Intensive Care Unit (NICU) admissions and contributes significantly to neonatal morbidity and mortality, particularly in resource-limited rural settings. Early identification of aetiological factors and timely respiratory support are crucial for improving outcomes. Aim: To study the clinical profile, associated risk factors, and outcomes of neonates admitted with RD in a rural tertiary care centre. Materials and Methods: The present hospital-based prospective cohort study was conducted in the NICU of Government Villupuram Medical College, Tamil Nadu, India between April 2020 and March 2021. A total of 120 neonates presenting with RD were included. Demographic data, perinatal risk factors, clinical presentation, aetiology, severity scores, respiratory support requirements, and outcomes were recorded and analysed. Statistical analysis was performed using the chi-square test to assess the association between risk factors and adverse outcomes. A p-value <0.05 was considered statistically significant. Results: Among the 120 neonates, 72 (60%) were male and 62 (51.7%) were preterm. Low-birth-weight was observed in 66 (55%) neonates. Caesarean section was the predominant mode of delivery, accounting for 74 (61.7%) deliveries. The most common aetiology was Transient Tachypnoea of the Newborn (TTN) in 38 (31.7%) neonates, followed by RD Syndrome (RDS) in 34 (28.3%), birth asphyxia in 22 (18.3%), and meconium aspiration syndrome in 14 (11.7%). Among term neonates, moderate to severe RD was seen in 38 (65.5%) neonates. Mechanical ventilation was required in 30 (25%), while 46 (38.3%) were managed with Continuous Positive Airway Pressure (CPAP). The overall survival rate was 92 (76.7%), with a mortality rate of 16 (13.3%). Prematurity, severe RD, sepsis and requirement of mechanical ventilation were significantly associated with adverse outcomes (p <0.05). Conclusion: Neonatal RD remains a major contributor to morbidity and mortality in rural tertiary care settings, with TTN being the most common cause. Strengthening antenatal care, early CPAP initiation, and strict infection-control practices may improve survival outcomes.