Journal of Pediatric and Neonatal Individualized Medicine (JPNIM)

The Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) was awarded a “Journal of high cultural value” prize by the Italian Ministry of Culture: the reasons of success

Vassilios Fanos — 2024-01-15

Dear Readers,

I would like to share with you the news that, in November 2023, the Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) was awarded a “Journal of high cultural value” prize by the Italian Ministry of Culture, through the General Directorate for Libraries and Copyright (with the decree D.D.G. n. 812, 16/11/2023). This is a great achievement as, in the biological-medical field, only a total of 3 journals were awarded by this decree.

This Editorial shows information about JPNIM, JPNIM Open Access policy, JPNIM Editorial Board, JPNIM indexing and archiving, the fact that JPNIM is the official journal of many Societies, JPNIM publication, JPNIM website views and JPNIM metrics.

Selected Lectures of the 3rd S.I.P.Ped. International Congress; Milan (Italy); November 29 - December 1, 2022

--- Various Authors — 2024-01-15

Selected Lectures of the 3^rd S.I.P.Ped. International Congress • QUALITY OF LIFE AND ASSISTANCE OF MINOR WITH CHRONIC DISEASE: FROM PRE-BIRTH TO ADOLESCENCE • Milan (Italy) • November 29^th - December 1^st, 2022

LECT 1. THE EXPERIENCE OF PEDIATRIC PSYCHOLOGY IN MATERNAL AND CHILD DEPARTMENT • G. Perricone, C. Polizzi (Palermo, Italy)

LECT 2. PEER RELATIONSHIPS AND ADOLESCENTS WITH CHRONIC DISEASE • A.M. La Greca (Coral Gables, FL, USA)

LECT 3. PARENTAL ETHNOTHEORIES AND CHILD CARING IN MIGRANT FAMILIES • G.G. Valtolina (Milan, Italy)

LECT 4. THE CENTRALITY OF THE CHRONIC CHILD IN ACCOMPANIMENT TO TREATMENT • G. Ragni, P. Becherucci, M. Lo Giudice, M. Picca (Latina, Florence, Palermo and Milan, Italy)

LECT 5. THE PEDIATRIC PSYCHOLOGIST IN DERMATOLOGICAL CHRONICITY. MULTIDISCIPLINARY WORK EXPERIENCE IN THE CLINIC OF ATOPIC DERMATITIS • A. Dattolo (Rome, Italy)

LECT 6. COULD THE NUTRITION OF THE PREGNANT WOMAN PREVENT DIFFERENT FORMS OF CHRONICITY? • F. Caturano (Turin, Italy)

LECT 7. QUALITY OF LIFE AND CARE OF A CHILD WITH CHRONIC PATHOLOGY: FROM PRE-NATAL LIFE TO ADOLESCENCE • F. Monti (Bologna, Italy)

LECT 8. TO CARE OF THE MINOR WITH NEURODEVELOPMENTAL DISORDERS IN THE TRANSITION TO THE ADULT PHASE • M.R. Morales (Varese, Italy)

LECT 9. THE POWER OF EPIGENETICS IN PERINATALITY • V. Fanos (Cagliari, Italy)

Pulmonary insufficiency of extreme prematurity (PIEP) and surfactant deficiency disease (SDD) – It is time to classify respiratory distress syndrome (RDS) in preterm neonates

Deepti Thandaveshwara — 2024-04-30

Respiratory distress in premature neonates is the consequence of various pathophysiologic conditions.

The respiratory distress syndrome (RDS) is commonly considered as the consequence of pulmonary surfactant deficiency; these babies generally respond well to exogenous surfactant.

In extremely premature babies, overall physiological immaturity of the lungs secondary to prematurity itself plays a significant role in respiratory illness; the therapeutic response to continuous airway distending pressure or surfactant is not very impressive in these babies, who continue to need an extended period of respiratory support and eventually end up in developing bronchopulmonary dysplasia.

This article aims to highlight the importance of the difference between primary surfactant deficiency disease (SDD) and pulmonary insufficiency of extreme prematurity (PIEP).

This classification may help in drawing up more appropriate treatment plans and reduce the gestation-related skewed outcomes in future research.

Pediatric oncological pain: the influence on the posture of the head and the spine. A narrative review

Andrea Scribante — 2024-02-06

Pediatric oncological pain (OP) is a common condition in children with cancer, resulting in postural changes in the head and spine, which significantly impact their quality of life. Osteosarcoma is the most prevalent type of pediatric tumor affecting head and spine districts. Its exact cause is still unknown, although it may be attributed to DNA mutations in bone cells, either inherited or acquired after birth; it often leads to bone and muscle pain and discomfort. This can initiate a harmful cycle, including mood disorders like anxiety and depression and maladaptive thoughts.

Conducting a thorough functional assessment of children with OP is crucial, involving clinical and psychological evaluations and multidisciplinary rehabilitative approaches. A physical evaluation of the head and spine primarily focuses on assessing motor abilities through inspection of joint mobility, muscle strength, palpation, reflexes, and sensitivity.

This narrative review considered randomized clinical trials, observational and cohort studies, and case reports; studies that did not meet inclusion criteria were excluded; 41 studies were selected for this review.

A team of healthcare professionals, including orthodontists, physiatrists, pediatricians, oncologists, and psychologists, collaboratively manage children with OP, aiming to minimize the physical and mental disability caused by OP. It is based on education, exercise therapy, and psychological approaches.

Education should include proper ergonomic postural guidance for sitting and standing, pain education (neuroscience education), and management of mood disorders and maladaptive thoughts (cognitive-behavioral education).

Exercise therapy should focus on active postural correction, including exercises to counteract forward head posture, hyperkyphosis, and swayback; strengthening exercises for spinal deep muscles; segmental stretching involving limbs and back muscles; and functional exercises.

Psychological therapy, particularly cognitive-behavioral therapy, involves cognitive restructuring, time-based activity pacing, relaxation techniques, and adaptive coping strategies.

This review provides a comprehensive overview of the clinical postural assessment of the head and spine, which is essential for planning effective multidisciplinary rehabilitative treatments.

Unlocking the secrets of metabolomics with Artificial Intelligence: a comprehensive literature review

Karolina Krystyna Kopeć — 2024-03-11

This comprehensive review synthesizes the wealth of scientific literature pertaining to the application of Artificial Intelligence (AI) in the field of metabolomics. Over the past decade, AI has played an increasingly pivotal role in deciphering the complexities of metabolomic data, offering novel insights into the molecular underpinnings of biological systems. Through an extensive examination of relevant research papers, we provide a comprehensive overview of the diverse AI techniques and methodologies, from data preprocessing and feature selection to predictive modeling and pathway analysis, employed in metabolomics studies. The review dissects key trends and advancements in AI-driven metabolomics, shedding light on its pivotal role in biomarker discovery, disease diagnosis, and personalized medicine. In addition to highlighting the significant contributions of AI to metabolomics, emerging frontiers will be explored, such as the incorporation of multi-omics data integration and the growing importance of explainable AI in biological research. Ultimately, this review underscores the transformative impact of AI on metabolomics, emphasizing its potential to reshape our understanding of metabolic pathways, disease mechanisms, and therapeutic interventions. The combination of AI and metabolomics stands as a powerful paradigm shift with far-reaching implications for advancing both fundamental scientific knowledge and practical applications across diverse domains.

The hemostatic system. 2nd Part

Doris Barcellona — 2024-04-30

The hemostatic system (HS) is crucial for human survival, both by preventing excessive bleeding and also through close links to the immune system. Both systems cooperate to defend us from attacks by microorganisms and viruses. However, the behavior of the HS changes radically in the presence of cancer, becoming its powerful ally. Excessive individual responses of the HS to sepsis or virus attacks also require further investigation. The current review aims to explain the main pathophysiological mechanisms responsible for the behaviors of the HS in inflammation and cancer. We address the three main components of the HS, i.e., platelets, blood coagulation, and fibrinolysis, separately, and provide detailed information on their different activities in relation to inflammation and cancer. A better understanding of the mechanisms underlying the HS may help to improve daily clinical practice. This review also considers the possible roles of anticoagulant and antifibrinolytic drugs in counteracting the abnormal reactions of the HS during the course of infectious diseases and cancer. Further ad hoc studies are needed to assess if these drugs can reverse or at least reduce the adverse impacts of the HS in infections and cancer.

Effect of antenatal betamethasone on early systemic inflammatory indices in preterm infants with gestational age < 32 weeks

Ufuk Cakir — 2024-02-24

Introduction: Antenatal glucocorticoid (AGC) therapy is routinely given to pregnant women when preterm delivery is expected. Systemic inflammatory indices are thought to have predictive value in some neonatal diseases. However, the effect of AGC on systemic inflammatory indices is unknown. The aim of this study was to evaluate the effect of AGC treatment on systemic inflammatory indices, morbidities and mortality in preterm infants.

Methods: All preterm babies born at < 32 weeks of gestation were evaluated retrospectively and included in the study. Systemic inflammatory indices, demographic characteristics and clinical results were compared by dividing the babies into groups based on the application of AGC to their mothers (24 mg betamethasone, 12 mg betamethasone and non-AGC).

Results: A total of 869 preterm infants were evaluated in the study. As the use of AGC increased, respiratory distress syndrome and mortality were found to decrease significantly (p < 0.001 and p = 0.018, respectively). No effect of AGC on other preterm morbidities and systemic inflammatory indices was detected (p > 0.05).

Conclusion: AGC had no effect on systemic inflammatory indices in preterm infants. The effect of AGC, especially on the lung, may be due to local effects rather than systemic effects.

Neonatal outcome of second-born twins: a 15-year retrospective study

Filipa Miranda — 2024-04-30

Objective: The aim of this study is to identify perinatal factors influencing the condition of the second-born twin.

Methods: A retrospective study of 15 years in a level 3 maternity center was conducted.

Results: The study included 1,176 twin pairs. The birth was eutocic in 26.4% of first-born and 27.8% of second-born twins, but cesarean section was more frequent in second-born twins. The average weight of the first-born twin was 2,097 g and that of the second-born 2,060 g, and this difference was influenced by maternal age and conception mode; 14.5% of first-born twins and 20.1% of second-born twins were small for gestational age (GA). There was a statistically significant difference in the 1st and 5th minutes Apgar scores between twins and the score in the 5th minute was influenced by chorionicity. There was no statistically significant difference in the number of admissions to the Neonatal Intensive Care Unit, length of stay or number of neonatal deaths. There was a statistically significant difference in the number of disorders, influenced by maternal age. We also found a significant difference in hyperbilirubinemia, glycemic status and apnea, but not in other disorders. The number of patients who underwent at least 1 procedure was higher in second-born twins (27.7% vs 25.2%) and was influenced by chorionicity. There was a difference in surfactant administration, but not in other procedures.

Conclusions: We found more cesarean sections in second-born twins, but more assisted vaginal deliveries in first-born twins. We also found statistically significant differences in relation to weight, size for GA, weight discordance, Apgar scores, and total number of disorders and procedures to which the twins were submitted. Chorionicity, conception mode and maternal age were of the most influence in these differences.

Ultrasound surveillance of fetal growth and wellbeing in maternal occupational tobacco handling – A cohort study

Rathika Damodara Shenoy — 2024-04-30

Introduction: Tobacco exposure during pregnancy has a negative influence on fetal growth. Maternal smoking causes placental vasoconstriction and fetal growth restriction (FGR). In India, the tobacco industry employs women to hand roll cigarettes called bidis. A bidi roller handles 120 g of tobacco and therefore 3 g of nicotine per day.

Aim: To evaluate the effect of occupational tobacco handling by pregnant women on fetal growth and wellbeing.

Methods: In this cohort study, 177 pregnant bidi rollers (exposed cohort) and 354 pregnant non-rollers (unexposed cohort) were followed up from 18-22 weeks of pregnancy until delivery with fetal sonogram and Doppler. Fetal surveillance data (including fetal biometry, Doppler indices, amniotic fluid index, biophysical profile and placentation) were recorded and compared. Maternal nicotine absorption was quantified by serum cotinine. Intergroup differences and relative risk (RR) were determined by Chi-square test (or Fisher exact when the count was ≤ 5), and adjusted odds ratio (OR) by binary logistic regression. Intrauterine growth trend was plotted.

Results: Fetal surveillance results were abnormal in 37.9% of the tobacco-exposed group, with a RR of 1.6 (p = 0.001) and adjusted OR of 1.8 (p = 0.005) in comparison with the unexposed group. Nicotine absorption was evident in 28.4% of the bidi rollers that had abnormal fetal surveillance results. The mean estimated fetal weight and head circumference demonstrated a sustained deceleration, starting at 28-30 weeks of gestation, in the exposed group. Doppler data suggested fetal adaptation to maintain cerebral circulation. We found a higher frequency of oligohydramnios (statistically significant), placental abruption (not statistically significant), and placenta previa (not statistically significant) in the tobacco-exposed group.

Conclusions: Occupational tobacco handling in bidi rollers resulted in early-onset symmetric FGR and compromised wellbeing. Pregnant women with any form of tobacco exposure require vigilant fetal surveillance.

Frequency and risk factors of bronchopulmonary dysplasia in low-birth-weight infants in Saudi Arabia: a 5-year experience

Ramadan A. Mahmoud — 2024-01-23

Background: Due to improved survival of extremely low-birth-weight (ELBW) infants, the frequency of bronchopulmonary dysplasia (BPD) has remained unchanged or even increased.

Objective: To study the frequency as well as the perinatal and neonatal risk factors of moderate-to-severe BPD and its related mortality in low-birth-weight (LBW) infants in a single-center study over 5 years in the Kingdom of Saudi Arabia (KSA).

Methods: A total of 461 LBW infants’ files with gestational age (GA) ≤ 32 weeks that met the inclusion criteria were retrospectively reviewed. Maternal and neonatal characteristics were evaluated. Furthermore, the hospital course of management of LBW infants and outcomes of mortality and morbidity were recorded.

Results: The overall mortality rate in LBW and ELBW infants was 19.52% and 38.62%, respectively. At 36 weeks’ corrected GA, the total BPD frequency in LBW and ELBW infants was 9.87% and 32%, respectively. BPD(+) cases had a lower mean GA and birth weight than BPD(-) cases, 26 ± 2.68 weeks, 830 ± 340 grams and 29 ± 2.56 weeks, 1,395 ± 470 grams, respectively (p < 0.0001). The BPD(+) group had a significantly higher maternal chorioamnionitis infection rate, 8/39 (20.51%), than the BPD(-) group, 25/356 (7.02%) (p = 0.004), higher late-onset sepsis (11 [28.21%] and 54 [15.17%], p = 0.04). BPD(+) cases had a significantly higher risk of intubation in the delivery room, more frequently more than one dose of pulmonary surfactant, more invasive ventilation on day 1 and day 7, more days on oxygen therapy, more days on invasive and non-invasive ventilatory support, more days of hospitalization (115.41 ± 92.14 days compared to 43.72 ± 27.98 days in BPD[-]; all p < 0.0001).

Conclusion: ELBW infants had a 2-fold higher rate of mortality and a 3-fold higher rate of BPD, compared with LBW infants. The frequency of BPD increased with low GA/birth weight and BPD(+) cases had a higher risk for intubation in the delivery room, received more frequently more than one dose of pulmonary surfactant, remained for more days on either invasive or non-invasive ventilatory support, and had longer hospital stays.

Sociodemographic characterization of the population from the maternity ward of a differentiated perinatal hospital in Portugal

Rafael Inácio — 2024-04-30

Introduction: Recently in Portugal, several social and demographic changes have been observed with an emphasis on the increasing number of foreign citizens. The linguistic, cultural and social barriers cause challenges to maternal and child health care. This study aimed to characterize the sociodemographic and obstetrical data of mothers and newborns hospitalized in the maternity ward of a tertiary hospital in the southern region of Portugal.

Methods: Cross-sectional observational study. A questionnaire was applied in the postpartum period to women admitted to the maternity ward of a tertiary hospital in Lisbon from 1 March 2021 to 30 June 2021.

Results: 347 surveys were obtained from a total of 785 hospitalizations. The average maternal age was 31.8 years and the average paternal age was 33.7 years. Most mothers (79.1%) and fathers (77.3%) reported having, at least, secondary education. 19.5% of mothers and 7.7% of fathers were students or unemployed, 18.9% of parents were unqualified workers and 32.0% of mothers and 23.4% of fathers were professionals in the group of intellectual and scientific activities. More than a quarter of our population were migrants (27.6% of mothers and 26.2% of fathers) and, of these, 14.9% of mothers and 11.2% of fathers were not fluent in Portuguese. 7.9% of pregnancies did not meet the criteria for adequate prenatal care defined at the national level. There was an association (p < 0.01) between inadequate pregnancy surveillance and lower maternal age and lower educational level. There was no difference between the migrant and non-migrant population regarding the completion of the prenatal care program.

Conclusions: The percentage of the migrant population is currently very expressive, with a non-negligible number of parents not fluent in Portuguese, which requires an adaptation of health resources to optimize the care provided. Lack of adequate prenatal care was expressive and was associated with lower maternal age and lower level of education.

Selective immunoglobulin A deficiency and recurrent infections in children: how deep is this issue?

Mirela Luminița Pavelescu — 2024-02-07

Background: Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency. Although most patients with SIgAD do not develop symptoms, some conditions related to SIgAD have been reported, particularly recurrent respiratory tract infections and infections caused by encapsulated microorganisms. Our objective was to evaluate the association of SIgAD with other pediatric conditions and extract data to establish an individualized protocol for managing patients with SIgAD.

Methods: We conducted a 3-year retrospective epidemiological study of 57 pediatric patients (aged 4-17 years) diagnosed with SIgAD after admission to the Pediatrics Department of “Grigore Alexandrescu” Emergency Children’s Hospital in Bucharest, Romania. The type of infection (location, etiologic agent, and severity) and associated allergic and immune disorders were analyzed.

Results: Respiratory tract infections were the main conditions observed in patients with SIgAD (86.0%), and recurrence was reported in over half of the patients (54.4%). Overall, 42.1% of patients had acute digestive involvement. Of the 93 infections (positive culture), in 37 cases (39.8%) encapsulated germs were involved. Among the encapsulated germs, Klebsiella pneumoniae was isolated in 11 cases (29.7%), Staphylococcus aureus in 9 cases (24.3%), Escherichia coli, Streptococcus pneumoniae and Haemophilus influenzae each in 5 cases (13.5%), and Pseudomonas aeruginosa was identified in 2 cases (5.4%). Several patients had recurrent or multiple infections – for 20 (35.1%) out of the 57 children, 2 microorganisms were identified at different points in time during the study period, and for 8 children (14.0%), 3 microorganisms were identified at the same time. Allergic-associated markers or allergic events were found in 20 children (35.1%) and celiac disease was diagnosed in 3 patients (5.3%).

Conclusions: Although SIgAD is a primary immunodeficiency that is not immediately life-threatening, infections are potentially disabling. Therefore, primary care physicians and pediatricians should closely monitor patients with SIgAD.

Value of maternal tactile method in detecting fever among under five years children during the COVID-19 era

Ali Adel Shareef — 2024-02-15

Objectives: The ability of mothers to accurately predict the presence of fever in their children using the tactile method is still controversial. This study evaluated the accuracy of Iraqi mothers’ tactile fever detection in children under 5 during COVID-19 pandemic.

Materials and methods: Interviews were conducted with 200 mothers whose children were under the age of 5 years and who assumed they had fever. Each mother was then asked to touch her child’s body for fever evaluation, while an investigator observed them, recorded their responses, and documented the places of palpation. Thereafter, the investigator determined the child’s temperature using a non-contact temple thermometer (NCTT). Statistical analysis was conducted to compare the maternal tactile approach to NCTT and single site to multiple site palpation in terms of sensitivity, specificity, and predictive values.

Results: The prevalence of fever in the study sample was 72%, as 144 of the 200 children involved were confirmed to have fever by NCTT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the maternal tactile method were 96.5%, 62.5%, 86.9%, and 87.5%, respectively. Multiple child body sites were palpated by 42.5% of mothers, whereas 57.5% palpated a single site, with the forehead being the most common palpated site (31%). Multiple site palpation had a significantly lower incorrect temperature assessment rate than single site palpation (3.5% vs. 27%, p = 0.00001). Additionally, the accuracy increased significantly when the mother palpated multiple sites (96.5% vs. 73%).

Conclusion: The findings of this study suggest that mothers’ use of tactile assessment is an effective screening tool when assessing their children’s fever; however, mothers’ fears can reduce the accuracy of this method, whereas instructing the mother to palpate multiple body parts can increase its reliability.

Clinical profile and outcome of COVID-19-positive children in a tertiary care centre of North-East India

Aditi Baruah — 2024-02-22

Introduction: COVID-19 infection is said to be generally a milder disease in children, compared to adults, and is associated with much lower case-fatality rates. Objective of this study was to find out the clinical characteristics and outcome of COVID-19-positive children and also the differences between the first and the second waves, if any.

Methodology: This was a retrospective study done in the Department of Paediatrics of a tertiary care teaching hospital. Departmental and hospital medical records were reviewed to assess the clinical characteristics, disease severity and outcome of all COVID-19-positive admitted children from May 2020 to September 2021 (the first wave from May 2020 to January 2021 and the second wave from April 2021 to September 2021). Data analyses were done in Microsoft® Excel® 2010.

Results: Out of total 560 COVID-19-positive children attending the hospital during the study period, 266 children (76 in the first wave and 190 in the second wave) were admitted. The majority of the children (25%) were in the age group of 1-6 months during the first wave, while in the second wave the majority of the children (27.9%) were in the age group of 5-10 years. The most common presenting complaint was fever (51.1%), followed by cough (13.9%). Co-morbidities were present in 23.3% of cases. Asymptomatic, mild, moderate, severe and critical cases were 16.5%, 51.9%, 18.4%, 6.4% and 6.8%, respectively. The case fatality ratio was 3.75% (21/560) among all positive cases. Ventilator support was required in only 10.1% of cases. There were some significant differences between the 2 waves regarding age distribution, disease severity, outcome and some presenting complaints.

Conclusions: The majority of the COVID-19 infections were either asymptomatic or of mild variety. Males suffered more than females. The admission rate was higher in the second wave but death was higher in the first wave, indicating higher infectiousness and milder nature of the disease in the second wave. Most of the deaths occurred within 24 hours of admission, indicating that late admission may be an important risk factor for mortality. Except for age distribution, severity and outcome, other parameters were comparable between the first and the second wave.

Compound heterozygous TRMU gene mutations in an infant with transient cholestasis and hyperlactatemia

Barbara Parma — 2024-02-13

The authors present an atypical case of an infant with unremarkable familiar, birth, and neonatal history who developed a mild/benign form of transient cholestasis. At admission, second- and third-level assessments were conducted, mitochondrial respiratory chain disorders were excluded. The patient was accurately and promptly diagnosed through a clinically driven genetic test. The genetic analysis evidenced a compound heterozygous mutation c.383A>G (p.Tyr128Cys) of maternal origin and c.835G>A (p.Val279Met) of paternal origin in the TRMU gene associated to transient infantile liver failure, a condition known for its progressive and sometimes fatal prognosis. Biochemical test and patient’s clinical evolution were both good and there was no evidence of liver failure or dysfunction of other organs. This is the first-ever reported case of a patient with a TRMU pathological compound mutation with such good clinical evolution.

Renal artery fibromuscular dysplasia: diagnostic challenges in a child presenting with hyponatremic hypertensive syndrome (HHS)

Asrar Abu Bakar — 2024-03-12

A 2-year-9-month-old boy presented with renovascular hypertension caused by middle-segment stenosis of the right renal artery, and a severe hypertensive crisis, accompanied by hyponatremia, hypokalemia, and transient proteinuria. Fibromuscular dysplasia (FMD) is the most common cause of renovascular disease in children. However, the diagnosis of FMD is often delayed because findings on renal sonograms with Doppler are frequently missed. A high index of suspicion is required to further investigate a renovascular cause when persistent hypertension in a child cannot be otherwise explained. We present the challenges of reaching a diagnosis in a resource-limited setting and discuss how a multidisciplinary approach was key to successfully manage a young child with renovascular disease.

New variant in the FBXL4 gene – leading to mitochondrial DNA depletion syndrome

Carolina Ferreira Gonçalves — 2024-04-30

Defects in the mitochondrial DNA (mtDNA) cause mtDNA depletion syndrome (MTDPS), a subclass of mitochondrial disorders that are genetically and phenotypically heterogeneous. MTDPS is a rare autosomal recessive disease caused by a mutation of a nuclear gene named FBXL4 (F-box and leucine-rich repeat protein 4), located on chromosome 6. This nuclear-encoded mitochondrial protein plays a vital role in mitochondrial bioenergetics, mtDNA maintenance, and mitochondrial dynamics. Pathogenic variants in the FBXL4 gene reduce mtDNA synthesis, resulting in a large decrease in the mtDNA content in cells, which is essential for normal energy production.

These pathogenic variants in the FBXL4 gene are associated with an encephalomyopathy MTDPS type 13 (MTDPS13), a rare and severe multisystemic disorder mainly characterized by infant-onset encephalomyopathy and lactic acidosis, developmental delay, hypotonia with feeding difficulties and failure to thrive. Other features may include the central nervous system and the ophthalmologic, cardiac, gastrointestinal, genitourinary, and immunological systems.

Herein, we report the case of an infant born to consanguineous Pakistani parents with an early onset of severe lactic acidosis, hypotonia, feeding difficulties, hypertrophic cardiomyopathy, supraventricular tachycardia, and transient neutropenia harboring a homozygous variant in the FBXL4 (c.370C>T [p.Q124*]) gene. This variant was identified in the patient’s parents in heterozygosity. He started medical treatment (with coenzyme Q10, propranolol, and sodium bicarbonate) and multidisciplinary support. As a result, a progressive improvement in postural tone and feeding autonomy was observed during the first months of life.

Therefore, encephalomyopathy MTDPS13 should be suspected when dealing with patients with severe congenital lactic acidosis and developmental impairment.