Glutaric Acidemia type I is an inborn error of metabolism that impairs the metabolism of lysine, hydroxylysine, and tryptophan, leading to neurologic and, as more recently described, acute and chronic kidney damage. This mini review explores the available literature regarding renal impairment in GA-1 and highlights the possible mechanisms involved. Most case reports regarding patients presenting acute kidney dysfunction indicate the tubules as the main site of impairment, which was also found in the animal model for this disease, especially under metabolic decompensation. In addition to that, a mild progressive decline in glomerular filtration rates has been found in GA-1 patients, independently of treatment quality and neurologic outcomes. Taken together, such findings reveal the importance of further investigation on the association between GA-1 and kidney function, encompassing the need for adequate therapeutic approaches and biomarkers that target these alterations.

Mitochondrial carbonic anhydrase VA (CA-VA) deficiency is a rare inherited metabolic disorder caused by biallelic variants of the CA5A gene. It presents with hyperammonemia, lactic acidosis, and ketonuria, with or without hypoglycemia. We report the long-term follow-up of the first two reported cases of CA-VA deficiency: a 16-year-old female (case 1) and her 14-year-old brother (case 2), both of whom presented with neonatal hyperammonemic encephalopathy, hypoglycemia, elevated lactate, ketonuria, and compensated metabolic acidosis. The diagnosis was made in both cases through the TIDEX study, which identified a homozygous pathogenic variant in the CA5A gene (c.697T>C, (p.Ser233Pro)). The clinical course of the index patient revealed three additional metabolic decompensation episodes (MDEs) triggered by intercurrent illnesses, with the last episode occurring at 8 years of age, highlighting the unusual timing of her MDEs compared to previously reported cases. Case 2 remained metabolically stable without any additional MDEs. These episodes were successfully treated with parenteral dextrose, a single dose of enteral carglumic acid, and occasionally parenteral lipids. Management of intercurrent illness included a sick-day formula high in carbohydrates and fats. Currently, both cases show normal growth, development, and neurological outcomes, suggesting a favorable prognosis, and in keeping with previously reported cases. Early diagnosis of CA-VA deficiency allows prompt treatment and prevents severe complications. With proper management, long-term outcomes are favorable, although severe and fatal outcomes have been reported. The impact on longevity needs to be assessed over longer durations. The development of consensus management for CA-VA deficiency is warranted.

Citrullinemia type I (CTLN1), caused by variants in the ASS1 gene, is characterized by life-threatening neonatal hyperammonemia. The severity of CTLN1 correlates with residual enzyme function: nearly absent activity leads to severe neonatal presentations, while partial function results in milder forms. The increasing identification of patients with mild citrullinemia highlights the need for a deeper understanding of its natural history, genotype-phenotype correlations, and long-term management strategies. This study aims to characterize the clinical and molecular features of mild citrullinemia and explore its implications for long-term management. We conducted a retrospective analysis of six pediatric patients diagnosed with mild CTLN1, examining their clinical presentations, biochemical parameters, and long-term outcomes. We present a case series of six patients (three males, three females; median age at presentation 0.5 years, median follow-up 8.5 years) identified through newborn screening (66.7 %), cascade testing (16.7 %), or symptomatic presentation (16.7 %). Consanguinity was present in half of the patients, including one sibling pair. None experienced metabolic decompensation. Baseline citrulline levels were mildly elevated (median 294 μmol/L) and ammonia levels ranged from mild to moderate (median 101 μmol/L; range 51-154 μmol/L). Arginine supplementation was administered to all patients at various stages without dietary protein restriction. Ammonia scavengers were used in three cases-two during the neonatal period and one at age 14 following neurological symptoms. Despite biochemical stability, half of patients had neurocognitive or psychiatric symptoms, including learning disabilities, obsessive compulsive disorder, attention deficit and hyperactivity disorder, and global developmentaldelay. Our findings indicate that, despite its classification as "mild", citrullinemia may involve underrecognized neurological risks, reflecting an incompletely understood pathophysiology. This underscores the importance of individualized treatment and long-termcare.

Methylmalonic acidemia is an inherited neurometabolic disorder characterized by accumulation of methylmalonic acid (MMA) in different tissues, particularly in the brain. As a result, patients frequently exhibit progressive neurological deterioration, accompanied by episodes of acute encephalopathy following metabolic decompensation. Astrocytes are glial cells that maintain the central nervous system homeostasis and may be important cellular targets of MMA-induced dysfunction. However, most in vitro experimental models for the study of methylmalonic acidemia are based on short-term exposure to the toxic metabolites that accumulate in patients. In this study, we used a prolonged experimental model, which has not been yet explored in the context of glial cells, focusing on the inflammatory response, glutamate metabolism, and putative signaling pathways that can contribute to understanding cellular damage observed in methylmalonic acidemia. It is emphasized that MMA is persistently elevated in the brain of the affected patients. Prolonged MMA exposure induced inflammation with significant increase in gene expression of cyclooxygenase 2, interleukin (IL)-1β and its receptor (IL1R1), and IL-6, accompanied by a decrease in IL-10 expression. MMA also increased glutamate uptake and the activity and gene expression of the enzyme glutamine synthetase, while it downregulated glial cell-derived neurotrophic factor (GDNF). The expression of NFκB, p38 MAPK, Nrf2, heme oxygenase 1, PGC-1α, and sirtuin 1 were also modulated by MMA treatment, indicating the critical role of these signaling pathways in the MMA-induced persistent gliotoxicity. Finally, it is conceivable that these changes may significantly contribute to clarify the pathogenesis of methylmalonic acidemia.

Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (n = 40) and those diagnosed after clinical presentation (n = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs.

Acute kidney injury (AKI) is a severe complication of traumatic brain injury (TBI) associated with poor prognosis. The glucose-to-potassium ratio (GPR), an emerging marker of metabolic stress, may play a role in post-TBI AKI, but its precise relationship is unclear. This retrospective cohort study investigated the association between early-admission GPR and AKI in 2,388 TBI patients from the MIMIC-IV database. Using multivariable logistic regression and restricted cubic spline (RCS) models, we explored both linear and non-linear associations. Of the patients, 56.7% (1,355/2,388) developed AKI. While a simple linear association between GPR and AKI was not significant after adjusting for confounders (P = 0.20), we discovered a significant non-linear "J-shaped" relationship (P for non-linearity = 0.012). The risk of AKI increased steeply once GPR surpassed an inflection point of approximately 30. A random forest model incorporating multiple clinical variables demonstrated significantly superior predictive performance (AUC = 0.808) compared to traditional logistic regression (AUC = 0.785; DeLong test P = 0.025). These findings reveal that a high GPR (> 30) acts as an independent non-linear risk indicator for post-TBI AKI, Rather than a direct driver of injury, an elevated GPR represents a valuable early warning signal for metabolic decompensation, suggesting clinicians should closely monitor high-risk patients to facilitate early recognition of AKI.

Abstract Purpose Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder frequently associated with sensorineural hearing loss (SNHL). Due to mitochondrial dysfunction, cochlear structures, especially the stria vascularis and outer hair cells, are susceptible to damage, causing progressive hearing impairment. Cochlear implantation (CI) offers rehabilitative potential, yet unique perioperative challenges related to anesthetic sensitivity and metabolic instability require tailored management strategies. Limited evidence exists regarding CI outcomes specifically in MELAS patients. This systematic review critically evaluates existing literature on CI efficacy, audiological outcomes, and perioperative considerations in MELAS. Methods A comprehensive systematic review following PRISMA guidelines was conducted. Databases including PubMed, Embase, Web of Science, and Scopus were searched for relevant studies reporting outcomes of CI in MELAS patients. Two independent reviewers performed article screening, data extraction, and risk-of-bias assessment. Results From 292 retrieved studies, 8 studies ( n = 10 patients) were included. Audiological outcomes consistently showed substantial improvement in speech perception tests post-CI. Standardized assessments demonstrated enhanced sentence and word recognition, alongside improved auditory-evoked potentials (ABR, MLR). Patients reported improvement in social engagement and communication. Surgical interventions were successful despite unique perioperative challenges related to MELAS pathology, including anesthesia complications and metabolic crises. However, existing studies primarily consisted of individual case reports, limiting generalizability. Conclusion Cochlear implantation is an effective rehabilitative option for patients with MELAS syndrome and severe-to-profound sensorineural hearing loss, improving speech perception and communication. Audiological outcomes and electrophysiological measures support its role in restoring auditory function in this unique population. However, given the risks of metabolic decompensation, anesthetic sensitivity, and perioperative electrolyte disturbances in MELAS, careful planning of anesthesia and surgical protocols is critical to patient safety.

Glycogen storage disease type Ia is a rare inherited metabolic disorder characterized by glucose-6-phosphatase deficiency. Hepatocellular adenoma development is a frequent complication in patients with this condition, with prevalence rates reaching up to 75%. The management of hepatic adenomas in these patients remains challenging due to risks of hemorrhage, malignant transformation, and surgical complications. Case Presentation We report a 22-year-old Chinese female with glycogen storage disease type Ia who presented with acute metabolic decompensation, including hypoglycemia (2.8 mmol/L), severe hyperlactatemia (20.0 mmol/L), and marked hypertriglyceridemia (31.78 mmol/L). The patient had been diagnosed with glycogen storage disease type Ia at age 5 and maintained on dietary therapy. At age 18, multiple hepatic adenomas were detected. Following intensive preoperative metabolic optimization and a comprehensive perioperative management protocol, she underwent successful indocyanine green fluorescence-guided left hepatectomy at age 22 with excellent postoperative recovery and no evidence of malignant transformation. This case demonstrates that hepatic adenomas in patients with glycogen storage disease type Ia can be successfully managed surgically with appropriate perioperative metabolic management. Early diagnosis, regular surveillance, and timely surgical intervention are crucial for preventing life-threatening complications in this patient population.

Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by a deficiency of branched-chain ketoacid dehydrogenase, the enzyme involved in the second step of branched-chain amino acid catabolism. Of the three branched-chain amino acids (leucine, valine, and isoleucine), accumulation of leucine is the predominant factor causing acute metabolic decompensation in patients with MSUD. In February 2025, eight expert physicians met to discuss the management of acute metabolic decompensation and propose recommendations after literature review (four guidelines and 20 other articles of interest). A practical clinical algorithm was established. Newborn screening was acknowledged to be a successful method of diagnosing MSUD at birth, facilitating early intervention to prospectively manage MSUD and reduce the frequency and severity of acute metabolic decompensation, although it was noted that infants with severe MSUD often present with acute metabolic decompensation before being diagnosed. The experts also identified several barriers to and gaps in the management of acute metabolic decompensation, and MSUD more generally, proposing potential actions to improve clinical outcomes. Acute metabolic decompensation requires prompt, effective treatment by a multidisciplinary team to ensure that circulating plasma leucine levels are rapidly reduced without causing complications (particularly cerebral edema). Where available, intravenous branched chain amino acid-free solutions (e.g., Maapliv, now approved in Europe) may represent an important treatment option. Adequate resources (treatments, laboratory services, dialysis units) are essential for effective management of acute metabolic decompensation. Liver transplantation is an accepted viable option for the long-term prevention of acute metabolic decompensation in eligible patients. Research is ongoing into new treatment options for MSUD, such as gene therapy. Optimal management of acute metabolic decompensation in patients with MSUD requires prompt, effective treatment to reduce leucine levels without causing complications. A ready-to-use branched chain amino acid-free intravenous solution has been recently approved in Europe and research into new treatment options is ongoing.

Objective: To investigate the clinical characteristics, genetic variants and outcomes of children with combined malonic and methylmalonic aciduria (CMAMMA) caused by ACSF3 gene variant. Methods: This was a retrospective case series. Clinical manifestations, biochemical findings, genetic sequencing and outcomes were collected from 7 infants with CMAMMA who were evaluated at the Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between December 2021 and November 2025. Blood acylcarnitine profiles were analyzed by tandem mass spectrometry, urinary organic acids by gas chromatography-mass spectrometry and causative variants by Sanger or next generation sequencing. Results: The cohort included 6 males and 1 female, with an age at onset of 1.0 (0.4, 8.0) years and 6 patients did not experienced acute metabolic decompensation during the neonatal or infantile period. Five patients had varying degrees of developmental delay, including 1 patient with seizures and 1 patient with hypotonia. Biochemical analysis revealed elevated urinary methylmalonic acid level in all patients, and 5 patients also had elevated urinary malonic acid levels. Plasma propionylcarnitine (C3) and homocysteine levels were within normal ranges in all patients, while a mildly increased C3/acetylcarnitine (C2) ratio was observed in 1 patient. Five patients were unresponsive to vitamin B12 therapy. Genetic analysis identified 11 ACSF3 gene variants, including 2 novel variants, c.785C>T (p.A262V) and c.889T>A (p.Y297N). Follow-up assessments showed 5 patients exhibited severe or borderline developmental delay, 1 patient developed normally and 1 patient died. Conclusions: CMAMMA caused by ACSF3 variants is characterized by marked phenotypic heterogeneity and a subset of patients experience unfavorable outcomes. The predominant biochemical finding is elevated urinary methylmalonic acid, with or without concurrent elevation of malonic acid, while blood acylcarnitine profiles were often within the normal range.

Interpreting variants of uncertain significance (VUS) is challenging in patients with atypical or transient metabolic presentations. We combined induced pluripotent stem cell (iPSC) models and minigene assays to characterize an ETFDH VUS (c.1049G > A) in a neonate who presented with acute metabolic decompensation characterized by fatty acid oxidation defects but showed normalized metabolic profiles by 14 months of age. Patient-derived iPSCs and minigene assays confirmed that c.1049G > A induces predominant exon 9 skipping, resulting in an in-frame 48-amino acid deletion within the FAD-binding domain. Structural modeling based on the human ETFDH crystal structure revealed that this deletion disrupts the core architecture of the FAD-binding domain, notably by eliminating the critical stabilizing interaction between Arg364 and Glu246, predicting compromised FAD binding affinity. Consistent with this structural defect, Western blot analysis showed markedly reduced ETFDH protein levels (< 10%) in patient cells versus heterozygous parents (~ 40%). Collectively, these data indicate that while the variant causes substantial molecular impairment explaining the neonatal crisis, the presence of residual protein likely supports metabolic homeostasis under non-stressful conditions. The c.1049G > A variant causes significant splicing disruption and partial protein loss, explaining the transient nature of the neonatal decompensation rather than a classic, persistent MADD phenotype. Furthermore, this study underscores the utility of iPSC models in resolving VUS cases where clinical biochemistry normalizes over time, bridging the gap between ambiguous genetic data and precise clinical management.

Loss of pyruvate carboxylase suppresses lethality in propionic acidemia.

IntroductionHereditary fructose intolerance is a rare but potentially severe and fatal disorder if it is not recognized promptly. It is caused by biallelic mutations in the ALDOB gene, which encodes the Aldolase B enzyme. Deficiency leads to intracellular accumulation of fructose‐1‐phosphate, causing secondary inhibition of gluconeogenesis and glucogenolysis and, consequently, hypoglycemia along with hepatic and renal dysfunction. The clinical presentation is variable and often nonspecific, making diagnosis challenging.Case reportA 12‐year‐old boy, born small for gestational age, with a history of hypotonia, laryngomalacia, and persistent hepatomegaly. During his first year of life, he developed an episode of acute hepatitis that required admission to a high‐dependency unit due to acute liver failure. Over the following years, he experienced recurrent episodes of vomiting, pallor, diaphoresis, and malaise following the ingestion of sweet foods. During follow‐up, he developed syncope secondary to severe hypoglycemia during a fructose tolerance test. Genetic testing revealed a homozygous pathogenic variant in the ALDOB gene, confirming the diagnosis of HFI. A strict diet excluding fructose, sucrose, and sorbitol was initiated, with close multidisciplinary follow‐up.ConclusionHFI represents a diagnostic challenge in pediatrics due to its clinical heterogeneity and its ability to mimic multiple hepatic and metabolic diseases. This case highlights the importance of considering HFI in patients with unexplained gastrointestinal and hepatic symptoms, even beyond infancy. Increased awareness and early diagnosis are critical to prevent misdiagnosis, avoid metabolic decompensation, and ensure excellent long‐term outcomes.

ABSTRACTSeryl‐tRNA synthetase 1 (SARS1) deficiency is a rare autosomal recessive disorder presenting with neurodevelopmental delay, deafness, cardiomyopathy, and fatal metabolic decompensation triggered by febrile episodes. While amino acid chronic supplementation is established, no guidelines exist for acute management. We report the case of a 9‐year‐old male of Turkish origin with genetically confirmed SARS1 deficiency, admitted with fever, vomiting, hypotonia, and seizures. The clinical course rapidly progressed to metabolic decompensation and severe acute cardiac failure, characterised by a left ventricular ejection fraction of 20%, necessitating mechanical ventilation and vasopressor support. Notably, the patient's family history included the death of three siblings during similar febrile episodes. During hospitalisation, the patient's specific L‐serine supplementation dosage was progressively tripled concurrently with standard supportive care. Unlike the fatal outcomes observed in his siblings, untreated by L‐serine, the patient survived and recovered following this high‐dose regimen. Cardiac biomarkers normalised within 20 days, and follow‐up echocardiography at 1 month demonstrated complete resolution of myocardial oedema. However, a year later, the patient presented with another febrile crisis at 10 years old, and despite an emergency protocol, the patient developed severe biventricular dysfunction progressing to fatal cardiogenic shock. This constitutes the first documented survival of a SARS1‐related metabolic crisis managed with high‐dose L‐serine. The findings strongly suggest that early, aggressive escalation of L‐serine dosage can be a viable therapeutic strategy for acute decompensation in SARS1 deficiency.

Inborn errors of metabolism (IEMs) are rare genetic disorders associated with increased vulnerability to infections and risk of metabolic decompensation. Although routine immunization is recommended, data on real-world vaccination status, seroprotection rates, and vaccine safety in children with IEMs remain limited. This study aimed to evaluate immunization status, antigen-specific seroprotection rates, determinants of seronegativity, and vaccine safety in a cohort of children withIEMs. This single center cross-sectional study was conducted at a tertiary Pediatric Metabolism Unit of Eskişehir Osmangazi University between January and June 2022. A total of 169 children were included. Vaccination history was obtained from immunization cards and parental report. Serological protection was assessed using commercial immunoassays and interpreted according to assay-specific cut-offs. Age eligibility and time since last vaccine dose were analyzed. Descriptive statistics were used to summarize immunization coverage and antibody levels. Group comparisons were performed using chi-square or Fisher's exact tests for categorical variables and non-parametric tests for continuous variables. A p-value <0.05 was considered statistically significant. A total of 169 pediatric patients (52.1 % girls; mean age 65.8±59.6months) were assessed through medical record reviews and caregiver interviews, with serological testing for vaccine-preventable diseases conducted via standardized ELISA assays. Overall, 94 % of children were vaccinated according to the national immunization program, and no vaccine-related metabolic decompensation or serious adverse events were observed. Six percent were unvaccinated or delayed, mainly due to hospitalization, neurological conditions, pandemic-related disruptions, or parental refusal. Only 9.5 % had received non-scheduled vaccines. Seroprotection was high for tetanus (100 %) and diphtheria (91.7 %). Lower seroprotection was observed for hepatitis B (68.0 %), hepatitis A (53.3 %) and varicella (47.4 %). However, seronegativity was strongly associated with longer time since last dose and ageineligibility for routine vaccination, rather than clear evidence of disease-specific impaired vaccine response. Although numerical differences were observed across metabolic subgroups, no consistent pattern of impaired vaccine response attributable to IEM category was identified. Children with IEMs demonstrated high overall vaccination coverage and reassuring safety profiles when immunized during metabolically stable periods. Observed immunity gaps were largely explained by programmatic factors, age eligibility, and time since vaccination. These findings support systematic vaccination review and selective serological assessment within routine metabolic follow-up while avoiding overinterpretation of seronegativity as disease-specific immune insufficiency.

Abstract Introduction Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of one of the most prescribed antidiabetic agents. It carries a high mortality rate and is often precipitated by kidney injury, infection, or concomitant toxin exposure. Momordica charantia, also known as bitter melon, is a popular herbal supplement believed to have glucose-lowering properties in many cultures. However, it contains cucurbitacins (triterpenoid compounds), which may be toxic, causing nausea, vomiting, abdominal pain, and hypotension. Case Presentation A 62-year-old man with a history of type 2 diabetes, hyperlipidemia, and hypothyroidism was transferred from an outside hospital in the setting of shock, renal failure, and lactic acidosis for continuous renal replacement therapy. He initially presented after several days of persistent nausea and vomiting. On presentation, he was normothermic, normotensive, tachycardic, and tachypneic. Over the next few hours, he became confused and lethargic. His physical examination was unremarkable; however, his laboratory studies were significantly abnormal. He was profoundly acidotic, with a pH of 6.74 and a pCO2 of 30 mmHg. His lactic acid level was above assay (&amp;gt;17 mmol/L) and had acute kidney injury with a BUN of 53 mg/dL, serum creatinine of 8.5 mg/dL, an anion gap of 34, and a serum bicarbonate of 6 mmol/L. Infectious workup was negative, and imaging did not reveal any acute pathology. Despite fluid resuscitation and empiric antibiotics, he continued to deteriorate, requiring intubation and transfer for emergent dialysis. Given his hemodynamic instability and need for vasopressors, he was started on continuous renal replacement therapy. Further discussion with his wife revealed that he had been on metformin for over two decades but had recently begun taking over-the-counter supplements and consuming large quantities of bitter gourd tea for glycemic control. The temporal relationship between his supplement use and clinical deterioration raised concern for a possible interaction contributing to his metabolic decompensation. He responded well to renal replacement therapy. After a prolonged ICU stay, he was successfully extubated, transferred to the medical floor with evidence of renal recovery, and ultimately discharged to a rehabilitation facility. Conclusion “Toxic squash syndrome,” a recognized complication of certain gourds, led to acute kidney injury through dehydration from GI loses that likely precipitated the development of MALA. This case underscores the importance of identifying the risks associated with commonly used dietary supplements and their potential interactions with prescription medications. Physicians should routinely inquire about supplement use and counsel patients on possible adverse effects. This abstract is funded by: None

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare single-gene disorders caused by enzyme defects that disrupt biochemical and metabolic pathways. Acute metabolic decompensation is a medical emergency that can be fatal if untreated. It can be triggered by catabolic stressors such as fasting, infection, surgery, pain, bleeding, or exposure to anesthetic agents. Traumatic injury in particular can precipitate IMD life-threatening crises. The risks of complicating surgical interventions can be reduced by careful perioperative management of fluids, nutrition, and medications under the guidance of a biochemical genetics specialist. Management of IMD metabolic emergencies is often complex, and trauma and surgical providers may only have limited access to specific protocols. Without prompt recognition and treatment, patients with IMDs are at high risk of poor outcomes in trauma or surgical settings. Optimal management requires early consultation with a metabolic specialist and a coordinated multidisciplinary team. This review highlights key principles and resources to enhance recognition and management of IMD metabolic crises for trauma and surgical teams.

Heart and heart-liver transplantation in Amish patients with propionic acidemia.

Background: Venomous animal injuries remain a relevant cause of severe systemic disease in tropical and subtropical settings. Renal involvement may occur both in previously healthy kidneys, leading to acute kidney injury (AKI), and in chronically diseased kidneys, precipitating severe decompensation and dialysis dependence. Objective: To describe four clinical cases illustrating the spectrum of renal involvement associated with venomous animal injuries, ranging from dialysis-requiring AKI to severe decompensation of pre-existing chronic kidney disease (CKD). Cases: We report four patients treated at a regional referral hospital in Paraguay. Case 1 involved a 44-year-old man with Loxosceles bite complicated by necrotizing fasciitis, septic shock, and AKI requiring 10 hemodialysis sessions, with fatal outcome after referral. Case 2 was a 33-year-old man with multiple wasp stings who developed anuric AKI, severe metabolic acidosis, hyperkalemia, respiratory failure, and death after 9 hemodialysis sessions. Case 3 involved an 81-year-old man with Bothrops snakebite and severe AKI requiring 12 hemodialysis sessions, with subsequent clinical and biochemical improvement. Case 4 was a 48-year-old man with probable spider bite and soft tissue infection, in whom advanced hypertensive CKD suffered severe metabolic and uremic decompensation, requiring repeated hemodialysis and progression toward chronic dialysis support.

Background: “Diabulimia” refers to intentional insulin restriction/omission in type 1 diabetes (T1D) to influence weight. It remains unrecognized in formal classification systems, complicating clinical coding. This behavior is a dangerous form of disordered eating linked to metabolic decompensation (recurrent ketoacidosis) and poorer prognosis. Aim: This article synthesizes evidence on diabulimia in adults with T1D, focusing on epidemiology, etiology, diagnostics, clinical presentation, complications, treatment, and prevention. Material and methods: A narrative synthesis was conducted using peer-reviewed reviews, observational studies, and case reports addressing: (I) insulin restriction as disordered eating, (II) acute metabolic crises (DKA), (III) chronic complications, and (IV) diagnostic challenges in adults (adult-onset T1D, LADA, secondary diabetes). Results: Diabulimia is characterized by weight-motivated insulin restriction and remains underdiagnosed due to a lack of formal criteria and overlap with diabetes distress. Evidence indicates a clinically meaningful prevalence of disordered eating in T1D adults, though data for older groups are limited. Reported outcomes include recurrent DKA and a rapid pathway to microvascular and neuropathic complications driven by chronic hyperglycemia. Conclusion: Diabulimia in adults is a high-risk condition at the interface of endocrinology and mental health. It requires interdisciplinary management, proactive detection of poor metabolic control, exclusion of diagnostic mimics (LADA/secondary diabetes), and combined psychological and diabetes-care interventions.