Intracerebral Calcifications Associated with Failure to Thrive and Macular Degeneration in an Adolescent: A Case Report.

Background: The clinical picture of intracerebral calcification is so varied that it constitutes an essential element of a wide range of clinical syndromes of variable expression that continue to be described. In this article, we discuss the diagnostic possibilities of basal ganglia calcification considering the association of failure to thrive and macular degeneration in our patient. Case: A 17-year-old male patient of Congolese origin consulted us for a pyramidal syndrome consisting of upper limb tremors during mobilization and dysgraphia. The patient also presented with a distance vision disorder for which the ophthalmological examination revealed poor visual acuity in both eyes (2/10) and macular degeneration in the left eye. On physical examination, we noted a short stature with a small head circumference in relation to age. The brain scan revealed the presence of bilateral striato-pallidal calcifications giving the appearance of Fahr's disease. However, the association of delay of stature development with microcrania, macular degeneration with reduced visual acuity and basal ganglia calcifications could suggest a wide range of syndromic hypotheses, the most likely of which is Rajab-type cerebral calcification. Conclusion: The association of failure to thrive, macular degeneration, and cerebral calcification of the basal ganglia is revealed as a particular phenotype compared to cases reported in the literature. An in-depth analysis would be necessary to identify a possible genetic basis.

[Geriatric failure to thrive: between illusory diagnosis and clinical reality]. / Syndrome de glissement : entre diagnostic illusoire et réalité clinique.

The geriatric failure to thrive, a controversial French concept not present in the international literature, was first characterized by Jean Carrié in 1956. It is described as a process of aging and physical and psychological decline associated with advanced age, manifesting as a pronounced overall deterioration. In this case report, we present the case of an 88-year-old patient, admitted to a general medicine service for geriatric failure to thrive, whose management eventually leads to the diagnosis of endocarditis with digestive cancer complicated by a characterized depressive episode. This case prompts us to consider the geriatric failure to thrive with extreme caution and challenges the legitimacy of such a diagnosis in the context of an aging population and the progress of medical sciences.

Palliative care considerations in frail older adults.

Frailty is a common geriatric syndrome characterized by a decline in physical and cognitive abilities and an increased vulnerability to stressors such as illnesses and injuries. As the global population is aging, the prevalence of frailty is growing. Frail older adults are at substantial risk of developing mobility and self-care difficulties, hospitalization, and death. Frailty is also associated with a high symptom burden and psychosocial stress, including malnutrition, pain, fatigue, weakness, cognitive loss, depression, falls, and sleep disorders, among others. The role of palliative care is gaining attention in medical literature because frailty is associated with increased morbidity and mortality. While there are no specific guidelines yet for when palliative care should be consulted in older patients with frailty, it has been proposed that palliative care should be considered in frail patients with continued functional decline, increased healthcare utilization, and uncontrolled symptoms. Palliative care can aid in communication with patients and families, establishing goals of care and treatment preferences, improving pain and symptom control, addressing psychosocial and spiritual needs, advance care planning, caregiver needs, and end-of-life care. Once frailty is identified, a comprehensive evaluation of the patient's physical, psychosocial, and spiritual aspects of care is essential for establishing a patient-centered treatment plan. This paper aims to guide clinicians in providing patientcentered care for older adults with frailty in the outpatient setting. Through a comprehensive literature review, we describe the leading models of frailty, frailty screening tools used in the clinical setting, and the assessment and management of palliative care needs in frail patients. We also describe emerging models of care focusing on palliative care for older adults with frailty and discuss issues related to access to palliative care for this population.

Shwachman-Diamond syndrome mimicking mitochondrial hepatopathy.

Shwachman-Diamond syndrome (SDS) is a genetic disorder caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. The syndrome is characterized by multiorgan dysfunction primarily involving the bone marrow and exocrine pancreas. Frequently overlooked is the hepatic dysfunction seen in early childhood which tends to improve by adulthood. Here, we report a child who initially presented with failure to thrive and elevated transaminases, and was ultimately diagnosed with SDS. A liver biopsy electron micrograph revealed hepatocytes crowded with numerous small mitochondria, resembling the hepatic architecture from patients with inborn errors of metabolism, including mitochondrial diseases. To our knowledge, this is the first report of the mitochondrial phenotype in an SDS patient. These findings are compelling given the recent cellular and molecular research studies which have identified SBDS as an essential regulator of mitochondrial function and have also implicated SBDS in the maintenance of mitochondrial DNA.

A Case Report on Tricho-Hepato-Enteric Syndrome: The SKIC3 Gene in Focus.

Tricho-hepato-enteric syndrome (THES), also known as syndromic diarrhea, is a rare genetic disorder that causes intractable diarrhea, hair anomalies, facial dysmorphism, and liver abnormalities. Herein, we report the case of an eight-month-old male who was referred to our hospital due to symptoms of diarrhea, vomiting, and insufficient weight gain. The child was born via cesarean section following an uncomplicated pregnancy, with no history of admission to the neonatal intensive care unit (NICU). Since birth, the patient has been experiencing diarrhea and inadequate weight gain, necessitating multiple hospital admissions. Upon evaluation, genetic testing confirmed the diagnosis of THES. The management strategy included a variety of nutritional interventions and supportive care measures. Currently, the patient is in the pediatric intensive care unit (PICU), receiving total parenteral nutrition (TPN) and continuous supportive care. This case underscores the complexity of diagnosing and managing THES, highlighting the need for comprehensive care and close monitoring of the patient's condition.

Autosomal Dominant Pseudohypoaldosteronism Type 1 in a Newborn With Failure to Thrive.

Pseudohypoaldosteronism type 1 is a rare genetic disorder characterized by salt wasting and resistance to mineralocorticoids due to mutations in the NR3C2 gene which codes for the aldosterone receptor proteins in the kidneys. This case study involves an infant who presented with poor growth and significant hyponatremia. There was improvement in growth and correction of hyponatremia with sodium supplementation, later found to carry a new genetic variant causing autosomal dominant pseudohypoaldosteronism type 1. A 14-day-old newborn presented with failure to thrive, severe hyponatremia, mild hyperkalemia, and metabolic acidosis. The electrolyte abnormalities were corrected with intravenous fluid and sodium supplementation. Continued oral sodium supplementation led to improved weight gain. Clinical suspicion and subsequent diagnostic testing led to a diagnosis of the autosomal dominant renal form of pseudohypoaldosteronism type 1. Genetic testing revealed a novel mutation on the NR3C2 gene, c.556_557del (p.Met186Valfs*3). The baby was discharged home on supplemental sodium and high-calorie formula for catch-up growth. Outpatient follow-up is ongoing.

Growth trajectories of children born preterm and full term with low birth weight to preschool ages: A nationwide study.

CONTEXT: Preterm (PT) and full term with low birth weight (FT-LBW) children are at a high-risk of poor growth outcomes. OBJECTIVE: To investigate the growth trajectories of PT and FT-LBW children from birth to preschool ages. METHODS: This study included 1,150,508 infants (PT, 41,454; FT-LBW, 38,250) who underwent the first three rounds (4-6, 9-12, and 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into Z-scores. Growth data at 2, 4, and 6 years old were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional-hazards regression analysis. RESULTS: The median birth weights of the PT, FT-LBW, and full term (FT) groups were 2.3, 2.4, and 3.2 kg, respectively. The incidence of short stature (height Z-score < -2 standard deviation score [SDS]) and failure to thrive (FTT) (body mass index (BMI) Z-score < -2 SDS) was the highest in the FT-LBW group, followed by the PT and FT groups. At 4 years old, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% for FTT. The ß estimate of height outcome was lower in both the PT (-0.326 SDS) and FT-LBW (-0.456 SDS) groups. CONCLUSIONS: The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group, highlighting the significance of growth monitoring in high-risk populations.

Characteristics and Outcomes of Failure to Thrive in Pediatric Patients Referred to the King Abdulaziz Medical City Pediatric Clinic.

BACKGROUND: Failure to thrive (FTT) in pediatric populations is a diagnostic challenge with implications for growth and development. Despite its prevalence, detailed epidemiological data, especially concerning organic versus non-organic etiologies, are sparse. This study examines the prevalence, characteristics, and outcomes of organic and non-organic FTT in a pediatric outpatient setting at King Abdulaziz Medical City, Jeddah. METHODS: This retrospective chart review included pediatric patients aged three months to 14 years diagnosed with FTT at KAMC from 2016 to 2023. FTT was defined by weights below the 3rd percentile or a decline across two major growth percentiles. Patients were stratified into organic and non-organic FTT groups based on predefined criteria. Prevalence rates, clinical characteristics, and outcomes were compared to draw distinctions between the two categories. RESULTS: Out of 349 evaluated patients, organic FTT was present in 160 patients (45.8%), with gastrointestinal conditions and endocrine disorders being the most common etiologies. Non-organic FTT, accounting for 189 (54.2%) of cases, was primarily associated with inadequate nutritional intake and behavioral factors. Notably, the non-organic FTT group exhibited a significantly higher rate of condition resolution (45.0%) compared to their organic counterparts (32.5%). Furthermore, significant laboratory parameter differences were noted, indicating a higher white blood cell count in organic cases, among other findings. CONCLUSIONS: Non-organic FTT was more prevalent and demonstrated higher resolution rates, suggesting better outcomes with timely intervention and appropriate care strategies. The study advocates for increased educational efforts for caregivers and healthcare providers and calls for further research to explore effective management protocols for FTT.

A rare case of congenital insensitivity to pain with anhidrosis.

A 22-month-old girl of consanguineous parents was admitted with a high-grade fever. She was found to have insensitivity to painful stimuli and an absence of perspiration. She also displayed self-mutilating behaviour and was insensitive to cold/hot water on her body. On examination, there was loss of the tip of the tongue, missing teeth, generalised xerosis, and several ulcers at sites of minor trauma. She also had dysplastic nails and digital ulcers. Sensory examination demonstrated a complete lack of awareness of pain and temperature, vibration and fine touch were intact and lacrimation was normal. Differential diagnoses of hereditary sensory and autonomic neuropathy (HSAN), Lesch-Nyhan syndrome, hypohidrotic ectodermal dysplasia and leprosy were considered. Results of routine blood investigations including serum uric acid were normal. On performing clinical exome sequencing, the diagnosis of congenital insensitivity to pain with anhidrosis (CIPA) of autosomal recessive inheritance was confirmed. A novel, predicted to be pathogenic variant detected at exon 16 of the NTRK1 gene resulting in congenital insensitivity to pain with anhidrosis is reported.Abbreviations: CIPA: congenital Insensitivity to pain with anhidrosis; HSAN: hereditary sensory and autonomic neuropathy; NGF: nerve growth factor; NTRK1: neurotrophic tyrosine kinase receptor 1 gene; TrKA: tropomyosin receptor kinase A.

Congenital Syphilis: A Case Report Presenting a Rare Clinical Manifestation in Two-Month-Old Newborn in Bahrain.

Congenital syphilis, caused by the Gram-negative obligate bacterium Treponema pallidum, can manifest as early- or late-onset infection, typically exhibiting classic symptoms such as a maculopapular rash, failure to thrive, and hepatosplenomegaly. This case report presents rare clinical manifestations of congenital syphilis not typically observed during early onset infection in a newborn in Bahrain. Additionally, it details the physical findings and investigations conducted to diagnose the disease.

Electrical Stimulation of Acupuncture Points Helps Resolve a Child's Failure to Thrive.

Background: Failure to thrive (FTT) is a challenging childhood condition that may lead to developmental delays and requires immediate therapeutic strategies. Children are diagnosed with FTT when their weight or rate of weight gain is significantly below that of other children of similar age and sex. A Pub Med literature search revealed no published acupuncture treatments for failure to thrive or faltering growth. Case: A 2 year, 4 month-old female was presented with FTT and a history of multiple severe congenital medical conditions. Western medical treatment with optimization of tube feeds achieved weight scores in the third-to-fifth percentile range. Acupuncture points were electrically stimulated for the child once monthly for 30 seconds with a Pointer Plus™ at each of 12 traditional Chinese/Shu Mu points and at several auricular points: Appetite, Stomach, Small Intestine, and Large Intestine bilateral. Results: The patient gained weight during the treatment, increasing monthly as shown on fully naked weight measurements to the 25th percentile, 28th percentile, 32nd percentile, 40th percentile, 46th percentile, 61st percentile, and 65th percentile. Her treatment was spaced to every 2.5 months after the 46th percentile measurement, and her weight started to level off when it reached the 61st percentile. Conclusions: In this particular case, electroacupuncture (EA) stimulation may have facilitated a weight gain in this female child. EA (nonneedle) research should be explored for FTT.

Infantile osteopetrosis with delayed development, organomegaly and wandering eyes: case report.

Osteopetrosis encompasses rare inherited metabolic bone disorders with defect in the osteoclast activity. Severe forms of presentation such as malignant infantile osteopetrosis are seen in infants and milder forms in older children. The clinical presentation includes failure to thrive, severe pallor, optic atrophy and hepatosplenomegaly. The disorder is characterised by dense bone on radiography, hence the name marble bone disease. A 10-month-old boy who presented with developmental delay, failure to thrive, nystagmus (which the mother described as wandering eye movements), splenomegaly of 16 cm and hepatomegaly of 8 cm. Investigations demonstrated severe anaemia (5.7 g/dL) and thrombocytopenia (34 x 109/L). Radiological signs which help in the diagnosis include diffuse sclerosis, bone within bone appearance, sandwich vertebrae and Erlenmeyer flask deformity. Plain radiography is an easily available and cost effective tool which can aid in the diagnosis of osteopetrosis.

Successful management of pylorospasm with atropine in a failure-to-thrive neonate case report.

Pylorospasm is an elusive diagnosis that can mimic the presentation of pyloric stenosis. There is limited discussion regarding its management in neonates with few case reports describing the use of antispasmodic agents. The following case reviews this management in a unique neonate. A 2-month-old female presented with persistent nonbilious, nonbloody emesis and failure-to-thrive. A thorough workup was performed due to its pronounced persistence while inpatient. Pyloric ultrasounds remained negative for pyloric stenosis; however, an upper gastrointestinal (GI) study was significant for pylorospasm. The workup also revealed hypothyroidism. Antispasmodic therapy with atropine was pursued as she was not a surgical candidate. Patient tolerated IV atropine therapy well with quick resolution of emesis and successfully transitioned to oral atropine therapy, displaying continued weight gain with exclusive oral feeds. This case displays a unique presentation of pylorospasm with successful management utilizing IV and oral atropine therapy in a neonate with failure-to-thrive and concomitant hypothyroidism.

Effectiveness of Postnatal Maternal or Caregiver Interventions on Outcomes among Infants under Six Months with Growth Faltering: A Systematic Review.

The care of infants at risk of poor growth and development is a global priority. To inform new WHO guidelines update on prevention and management of growth faltering among infants under six months, we examined the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants between 0 and 6 months. We searched nine electronic databases from January 2000 to August 2021, included interventional studies, evaluated the quality of evidence for seven outcome domains (anthropometric recovery, child development, anthropometric outcomes, mortality, readmission, relapse, and non-response) and followed the GRADE approach for certainty of evidence. We identified thirteen studies with preterm and/or low birth weight infants assessing effects of breastfeeding counselling or education (n = 8), maternal nutrition supplementation (n = 2), mental health (n = 1), relaxation therapy (n = 1), and cash transfer (n = 1) interventions. The evidence from these studies had serious indirectness and high risk of bias. Evidence suggests breastfeeding counselling or education compared to standard care may increase infant weight at one month, weight at two months and length at one month; however, the evidence is very uncertain (very low quality). Maternal nutrition supplementation compared to standard care may not increase infant weight at 36 weeks postmenstrual age and may not reduce infant mortality by 36 weeks post-menstrual age (low quality). Evidence on the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants under six months with growth faltering is limited and of 'low' to 'very low' quality. This emphasizes the urgent need for future research. The protocol was registered with PROSPERO (CRD42022309001).

Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma.

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases. METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6KozakGAL4 allele to assess the expression pattern of dYkt6. RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, developmental delay, and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual is homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] and exhibited neurodevelopmental disorders and optic atrophy. Fly dYkt6 is essential and is expressed in the fat body (analogous to liver) and central nervous system. Wild-type genomic rescue constructs can rescue the lethality and autophagic flux defects, whereas the variants are less efficient in rescuing the phenotypes. CONCLUSION: The YKT6 variants are partial loss-of-function alleles, and the p.(Tyr185Cys) is more severe than p.(Tyr64Cys).

Fallo de medro en Pediatría de Atención Primaria: recomendaciones para su abordaje y seguimiento / Failure to Thrive in Primary Care pediatrics: recommendations for its approach and follow-up

El fallo de medro representa la dificultad para mantener un ritmo de crecimiento adecuado, tanto en peso como en talla, en menores de tres años. Se trata de una entidad actualmente infradiagnosticada que puede repercutir en el desarrollo físico, intelectual, emocional y social de los niños. El pediatra de Atención Primaria es clave en la identificación precoz y en la prevención de su morbilidad. Este documento representa una herramienta útil para el desarrollo de la labor conjunta del pediatra y la enfermería pediátrica, realizando una intervención precoz, individualizada y eficiente en estos niños. (AU)

Failure to thrive is poor physical growth, both in weight and height, in children under three years of age. This underdiagnosed entity can affect children’s physical, intellectual, emotional and social development. Paediatric Primary Care is crucial in early diagnosis and prevention of their morbidity. This document represents a useful tool for the teamwork between paediatricians and paediatric nursing. Its objective is to carry out an early, individualized and efficient approach in these children. (AU)

Failure to thrive in pediatric patients with congenital heart disease: a cross-sectional study of 13,256 patients.

Background: The prevalence and risk factors for failure to thrive (FTT) in pediatric patients with congenital heart disease (CHD) remain ambiguous. We aimed to investigate the prevalence, growth profiles, risk factors, and vulnerable subtypes of CHD associated with FTT in pediatric patients with CHD. Methods: This was a cross-sectional study based on Chinese Database for Congenital Heart Surgery. FTT was defined as either stunting or underweight (height or weight standard deviation score <-2), and they were standardized by references of normal Chinese population. Risk factors was determined with logistic regression model, and growth profiles were delineated in each subgroup. Findings: A total of 13,256 CHD patients were included in this study, with 3994 patients of mild CHD, 7195 patients of moderate CHD and 2067 patients of complex CHD. The prevalence of stunting, underweight and FTT was 24%, 29.3% and 36.9%, respectively. Preoperative anaemia, left ventricle systolic dysfunction, younger age, more complex CHD types, lower birth weight and genetic syndrome were found to be the risk factors for FTT in CHD patients. Interrupted aortic arch was revealed to be the most severe group associated with FTT. Interpretation: FTT is ubiquitous in patients with CHD and exacerbated in high-risk subgroups. Our findings hinted the necessity of early identification and intervention for FTT in patients with CHD during daily practice of pediatrics, as it has the potential to improve outcomes and enhance their quality of life. Furthermore, we advocate for the initiation of prospective research with longitudinal data to comprehensively investigate the association between FTT and CHD across the lifespan. Funding: This study was supported by National High Level Hospital Research Funding (2022-GSP-GG-19), Capital Health Research and Development of Special Fund (2022-1-4032) and National Key R&D Program of China (2022YFC3600202 and 2022YFC3600203).

Congenital lobar emphysema: A diagnostic dilemma with coexistent congenital heart defects.

Key Clinical Message: Clinicians should think beyond pneumonia and left-to-right shunts when young children have persistent respiratory distress. Congenital lung anomalies, including congenital lobar emphysema, should be considered differential diagnoses. Chest X-ray and CT imaging should be conducted to gain insight regarding and establish diagnosis, respectively. Abstract: Congenital lobar emphysema (CLE) is a rare and life-threatening congenital lung anomaly that often poses a diagnostic dilemma. The issue can be further confused with coexistent congenital heart defects (CHDs) with left-to-right shunts. The clinical presentation of CLE during infancy is similar to that of CHD, with CHD being more common entity, gets detected early. The presence of underlying CLE may only be suspected after CHD repair. In our case, a 2-month-old infant presented with respiratory distress. On evaluation, a large ventricular septal defect and patent ductus arteriosus were detected. After successful cardiac defect repair, the infant continued to experience cough, respiratory distress, and failure to thrive. Furthermore, on radiological reanalysis, CLE was suspected on X-ray and confirmed via computed tomography. CLE can be detected on chest X-rays; however, at an early stage, it is often confusing and misleading.

Chronic diarrhoea due to trichohepatoenteric syndrome (THES) in an infant.

An infant was admitted with suspected postinfectious malabsorption with watery diarrhoea, fever and failure to thrive. She had dehydration, acute kidney injury and metabolic acidosis, which were corrected with intravenous fluids and managed with empiric antibiotics and prophylactic antifungals. She also developed Escherichia coli sepsis, meningitis and Candida skin infections during hospitalisation, which were treated according to the culture reports. Intrauterine growth restriction, woolly hair and a broad nasal bridge with chronic refractory diarrhoea prompted genetic testing to rule out syndromic diarrhoea. Whole-exome sequencing revealed a pathogenic compound heterozygous mutation causing trichohepatoenteric syndrome. She succumbed to severe infections at 80 days of life. The condition is rare, and no established guidelines or specific treatments exist; the focus is to promote optimal growth through parenteral nutrition, elemental formula and infection control. Early suspicion and molecular genetic testing can help reduce the time to diagnosis, treatment and genetic counselling.