Metabolic Specialists Research Articles

Refeeding syndrome (RFS) is defined as a set of metabolic and electrolyte abnormalities after nutrition initiation following prolonged starvation or protracted vomiting. Metabolic and bariatric surgery (MBS) and the associated rapid weight loss have been proposed as potential triggering factors for RFS. This study aimed to examine the currently available literature and provide an overview of the reported cases of RFS in patients who underwent metabolic and bariatric surgery. We performed a systematic screening of Embase, Medline, and Scopus until June 2024. The review was conducted according to PRISMA guidelines. We identified a total of nine patients with RFS who had a history of metabolic and bariatric surgery with a median age of 38years (IQR 32-44). Five participants (55.5%) were females, and two were males (22.2%). Adjustable gastric banding was the main bariatric procedure performed in almost half of the patients (44.4%, 4/9) followed by Roux-en-Y gastric bypass (22.2%, 2/9). Post-operatively, all patients experienced weight loss that ranged from 29.7% to 78.1% total percentage weight loss. The most common symptoms included vomiting (44.4%, 4/9) and abdominal pain (22.2%, 2/9). Most patients (66.6%, 6/9) received vitamin supplementation, followed by electrolyte replacement (55.5%, 5/9). Most patients (88.8%, 8/9) improved, and one patient died (11%, 1/9). Refeeding syndrome is a rarely reported complication after metabolic and bariatric surgery, but as the frequency of MBS increases, RFS is expected to become more common. Clinical awareness among bariatric and metabolic specialists is important for the identification of high-risk individuals as well as for the early diagnosis and adequate management of patients with RFS.

Maple Syrup Urine Disease (MSUD) and Type 1 Diabetes Mellitus (T1DM) are two distinct metabolic disorders with unique dietary management requirements. While MSUD necessitates strict restriction of branched-chain amino acids (BCAAs), T1DM requires precise carbohydrate counting to maintain optimal glycemic control. We report two cases of patients diagnosed with both MSUD and T1DM, highlighting the challenges and strategies in dietary management. Case 1, a 5-year-old girl, was diagnosed with T1DM after presenting with hyperglycemia and metabolic acidosis, despite previously stable MSUD management. The dietary regimen was modified to include a leucine-free amino acid formula and controlled carbohydrate intake to stabilize both leucine and glucose levels. Case 2, an 11-year-old boy with the diagnosis of MSUD, presented with hyperglycemia during a routine follow-up. Dietary management involved increasing the leucine-free formula while reducing carbohydrate intake to maintain metabolic control. Both cases emphasize the importance of individualized dietary plans, integrating BCAA restriction and carbohydrate regulation to prevent metabolic crises and achieve optimal glycemic control. These cases also underscore the need for a multidisciplinary approach involving pediatric endocrinologists, metabolic specialists, and dietitians to navigate the complexities of dual metabolic disorders effectively. Further studies are warranted to explore long-term outcomes and potential therapeutic targets in patients with concurrent MSUD and T1DM.

Adults with inherited metabolic disorders (IMD) are a growing patient group. In the Netherlands, adult IMD patient numbers increased fourfold over the past 15 years, from 846 to 3518 individuals, divided over 160 different disorders. The most common disorders are mitochondrial diseases, phenylketonuria and Fabry disease. Approximately half of the patients are diagnosed after age 16. Adult IMD patients require specific care, provided by adult metabolic specialists. Those specialists include, but are not limited to, internists, endocrinologists, neurologists and dieticians. The application of new diagnostic tools, enabling measurement of a large panel of metabolites and assessment of large part of the genome, have greatly improved IMD diagnostics. Better recognition of adults with IMDs, combined with new treatment modalities, will improve quality of life of adults with IMD in the decades to come.

ABSTRACTThe concept of IMDs has evolved over a century from rare deficits in amino acid catabolism diagnosed by the accumulation of biochemical markers such as phenylketonuria (PKU) to diseases affecting organelle metabolism, synthesis of complex molecules, and cellular trafficking. Small‐molecule accumulation disorders form the major group of treatable IMDs. Do not miss these metabolic emergencies! IMDs currently number over 1800 and include all medical specialties. The specificity of true “molecular internists,” metabolic specialists, lies in the in‐depth knowledge of metabolic pathways and the understanding of the pathophysiology of the deficits underlying the treatments (“precision medicine”). Neurology is massively impacted, but cerebral metabolism remains largely misunderstood. Genetic analyses are becoming increasingly important for diagnosis but must be complemented by biochemical investigations, which sometimes have greater diagnostic specificity and provide functional information at the phenotype level. Biochemical analyses remain essential for monitoring treatment or even for diagnosis. Finally, contrary to early expectations, newborn screening such as that for phenylketonuria, leading to preventive therapy, could be extended to a significant though limited number of IMDs. Currently, there are numerous initiatives that include genetic screening combined with biochemical testing or that extend screening to lysosomal diseases potentially treatable by enzyme or gene therapy.

Objective: Inherited metabolic disorders (IMDs) are rare genetic disorders with complex clinicalpresentations. Due to their rarity and limited presence in medical education, there is a lack of knowledge and increased anxiety among physicians in the management of these diseases. This study aims to evaluate the knowledge and anxiety levels of physicians about IMDs and to determine the factors affecting their professional competence.Method: A cross-sectional survey was conducted with the participation of 83 physicians across Türkiye. Participants completed an online questionnaire assessing demographic data, knowledge of IMDs, and anxiety about these diseases. The data were analyzed using statistical methods such as t-tests and chisquare tests.Results: The mean knowledge level of physicians was 5.6 ± 2.1 on a 10-point scale, indicating that they had basic knowledge but lacked advanced knowledge. The mean anxiety score was 5.3 ± 2.4, and the most common cause of anxiety was reported as lack of knowledge by 60.2%. It was observed that physicians who saw IMD patients less frequently perceived their level of knowledge to be higher than it was due to their inability to adequately recognize the complexity of these diseases. Although the presence of a metabolic specialist in the institution increased self-confidence, it did not have a significant effect on knowledge and anxiety levels.Conclusion: This study highlights the importance of systematic educational programs in IMD management by revealing physicians’ lack of knowledge and increased anxiety levels. Interactive case-based learning, preparation of national guidelines, and interdisciplinary collaboration are critical to increasing knowledge and improving patient outcomes.Cite this article as: Enver EÖ, Yılmaz B. Evaluation of physicians’ knowledge and anxiety levels about inherited metabolic diseases: survey study. Cerrahpaşa Med J. 2025, 49, 0006, doi:10.5152/cjm.2025.25006.

Rickets is a disorder of defective bone mineralization resulting in skeletal deformities, growth retardation, and increased risk of fractures. Nutritional rickets, once a historical disease, has reemerged in select pediatric populations despite modern food fortification efforts. Many of the most common food allergens - dairy, eggs, and fish - are primary dietary sources of vitamin D, which presents a unique risk factor for development of rickets. Children with multiple food allergies are at a heightened risk, particularly if their diets are not adequately supplemented. This case report describes a 2-year-old male with multiple food allergies who developed vitamin D-deficient rickets. He was referred to a pediatric orthopedic surgeon by his primary care physician due to concerns about progressive bilateral bowing of his legs. Radiographic evaluation of the lower extremities revealed characteristic findings consistent with nutritional rickets, including irregular cupping, fraying, and flaring of the metaphyses at the distal femur, tibia, and fibula bilaterally. Laboratory testing confirmed a biochemical profile consistent with severe vitamin D deficiency and impaired bone mineralization. The patient's serum calcium level was 9.0 mg/dL and serum phosphorus level was 2.9 mg/dL. Alkaline phosphatase level was markedly elevated at 1060 U/L and serum 25-hydroxyvitamin D level was critically low at 4 ng/mL. Treatment was initiated with high-dose vitamin D supplementation at 6000 IU of cholecalciferol daily. Additionally, dietary counseling was emphasized, and follow-up was arranged with pediatric endocrinology, a metabolic specialist, and orthopedic follow-up is ongoing to evaluate for correction or progression of the bowing. This case highlights the intersection of pediatric metabolic bone disease and food allergies, emphasizing the need for heightened awareness of nutritional deficiencies in children with restricted diets. Despite public health advances, vitamin D-deficient rickets continues to emerge in select populations, underscoring the necessity for early diagnosis, supplementation, and interdisciplinary management.

Improving acute care for Primary Mitochondrial Disease: Development of a publicly available clinical care pathway.

Acquired glutaric aciduria type II (GAII) is an emerging metabolic disorder linked to mitochondrial dysfunction, which may predispose patients to recurrent pancreatitis due to impaired fatty acid metabolism. This report presents the first documented instance of recurrent acute pancreatitis in a patient with acquired GAII. A 30-year-old Caucasian female with a known diagnosis of acquired GAII presented with recurrent episodes of acute pancreatitis, including two episodes during pregnancy and one outside pregnancy. Thorough investigations systematically excluded common causes such as gallstones, alcohol use, hypertriglyceridemia, IgG4-related disease, autoimmune pancreatitis and anatomical anomalies. Management required multidisciplinary collaboration involving surgeons, obstetricians, metabolic specialists and medical physicians. Treatment involved conservative surgical management including intravenous fluid resuscitation, analgesia, anti-emetics and specialized metabolic support, particularly intravenous dextrose while fasting. This case highlights the importance of recognizing acquired GAII as a potential underlying cause of recurrent acute pancreatitis. Awareness among surgical and multidisciplinary teams is crucial for timely diagnosis and effective management to prevent severe complications.

Interdisciplinary perspectives on the co-management of metabolic dysfunction-associated steatotic liver disease and coronary artery disease.

Time-restricted eating (TRE) shows promise for managing weight and metabolic issues, yet its application in real-world healthcare settings remains underexplored. This study aims to assess the real-world utilisation and short-term outcomes of TRE in clinical practice. This observational study used a retrospective chart review of 271 adults who attended a metabolic specialist clinic between 2019 and 2023. Descriptive statistics and multivariable logistic regression were used to identify factors associated with TRE adoption, while paired sample t-tests evaluated changes in outcomes among those who received TRE advice. Among the 271 patients, 76% were female, 90% Caucasian, and 94% overweight/obese. Of all patients, 47.2% received TRE advice, mainly using the 16:8 method, alongside additional dietary guidance for 60% of patients. Working status and baseline metabolic profiles were the only factors significantly associated with TRE adoption. Among those who followed TRE, 81% experienced modest but significant reductions in weight (-1.2 kg, p < 0.01), BMI (-0.4 kg/m2, p < 0.01), and waist circumference (-3.7 cm, p < 0.01). This study highlights TRE as a feasible and practical dietary strategy for improving metabolic health in healthcare settings. However, further research and improved data capture are needed to explore long-term adherence, potential adverse effects, and the effectiveness of TRE across diverse patient populations.

Diabetes is a chronic condition that requires constant blood glucose self-monitoring. The carbohydrate metabolism compensation is usually assessed by the level of glycated hemoglobin. But it does not always help reveal the true cause of poor glycemic control. The devices for continuous glucose monitoring allows to assess blood glucose level in real time and find unusual causes of hyper- and hypoglycemia. Achieving target glycemic levels is influen­ced by many factors: age of patients, duration of diabetes, eating habits and eating disorders, level of education, patient’s understan­ding of the diabetes course. One of the reasons for not reaching the target levels of glycemia can be hyperphagic eating disorders, such as night eating syndrome. According to the American Psychiatric Association classification, night eating syndrome belongs to the category of “Other specified eating disorders”. Diagnostic criteria in this syndrome include consumption of &gt; 25 % of food from the daily diet after dinner or at least 2 cases per week of food consumption at night; awareness of these episodes; and at least 3 of the following: morning anorexia, uncontrollable desire to eat between dinner and sleep or at night, conviction that eating will help you fall asleep or return to sleep, insomnia and/or bad mood in the morning. The prevalence of night eating syndrome in the general population is 1.1 %, and in those who refer to metabolic surgery specialists, it is 2–20 %. The presence of night eating syndrome in diabetes adversely affects metabolic control and complicates the management of these patients, in particular, they have higher levels of HbA1c, blood pressure and body mass index compared to individuals without such eating disorder. In this case report, we describe a patient with poor glycemic control who used continuous glucose monitor and was diagnosed with night eating syndrome that helped change management and achieve normoglycemia in the evening and nighttime.

IntroductionOsteogenesis imperfecta (OI) is a heritable skeletal disorder and comprises various subtypes that differ in clinical presentation, with Type I considered the least severe and Types III/IV the most severe forms. The study aim was to understand the OI patient diagnostic and treatment journey across Europe.MethodsWe conducted a qualitative, descriptive study to understand the OI patient journey. A selection of people with OI/their caregivers and clinicians involved in OI-patient care from across Europe were interviewed using a specially developed questionnaire.ResultsBetween May 2022 and July 2022, 22 people with OI/caregivers and 22 clinicians (endocrinologists, orthopaedic surgeons, geneticists and metabolic specialists) from across Europe were interviewed. Our study showed various areas of concerns for the OI community. Timely diagnosis of OI is essential; misdiagnoses and a delay to treatment initiation are all too common. There are a lack of consensus guidelines regarding optimal treatments (including when bisphosphonate therapy should be initiated and the route of administration) and patient management throughout the duration of the patient’s life. Adult OI patients do not have a medical home and are often managed by endocrinologists and rheumatologists. Adult care is often reactive based on the development of new symptoms. The psychosocial burden of OI impacts on the patient’s quality of life.ConclusionsThere is an urgent need for increased awareness about OI and its wide range of symptoms. In particular, there is a need for consensus guidelines outlining the optimum care throughout the duration of the OI patient’s life.

Standardized emergency protocols to improve the management of patients with suspected or confirmed inherited metabolic disorders (IMDs): An initiative of the French IMDs Healthcare Network for Rare Diseases

Dihydrolipoamide dehydrogenase (DLD) deficiency is an ultra-rare autosomal-recessive inborn error of metabolism, affecting no less than five mitochondrial multienzyme complexes. With approximately 30 patients reported to date, DLD deficiency was associated with three major clinical presentations: an early-onset encephalopathic phenotype with metabolic acidosis, a predominantly hepatic presentation with liver failure, and a rare myopathic phenotype. To elucidate the demographic, phenotypic, and molecular characteristics of patients with DLD deficiency within the Israeli population, data were collected from metabolic disease specialists in four large tertiary medical centers in the center and south of Israel. Pediatric and adult patients with biallelic variants in DLD were included in the study. A total of 53 patients of 35 families were included in the cohort. Age at presentation ranged between birth and 10 years. Wide phenotypic variability was observed, from asymptomatic individuals in their sixth decade of life, to severe, neonatal-onset disease with devastating neurological sequelae. Six DLD variants were noted, the most common of which was the c.685G>T (p.G229C) variant in homozygous form (24/53 patients, 45.3%; 13/35 families), observed mostly among patients of Ashkenazi-Jewish descent, followed by the homozygous c.1436A>T (p.D479V) variant, found in 20 patients of Bedouin descent (37.7%; 16/35 families). Overall, patients did not necessarily present as one of the previously described distinct clinical phenotypes. DLD deficiency is a panethnic disorder, with significant phenotypic variability, and comprises a continuum, rather than three distinct clinical presentations.

Abstract Trimethylaminuria (TMAU) is a rare metabolic disorder resulting in the accumulation of trimethylamine (TMA), which is a foul-smelling metabolite that is excreted in bodily fluids and exudes a characteristic odour of rotting fish. Although the condition is not life-threatening, the psychological and social consequence can be devastating. Herein, we present the case of a 35-year-old woman with a diagnosis of TMAU. This case outlines the methods by which a diagnosis of TMAU can be made, while also magnifying the negative psychosocial impact of this rare diagnosis. It also reflects real-world experience with the currently available therapeutic options. TMA is produced in the gastrointestinal tract from dietary precursors such as choline (present in eggs, liver and poultry), trimethylamine N-oxide (TMAO; found in marine fish) and carnitine (found in meat). Primary trimethylaminuria is due to a mutation in the FMO3 gene, leading to the inability to oxidize this amine to the nonodorous metabolite (TMAO) (Antoñanzas J, Querol-Cisneros E, Alkorta-Aranburu G et al. Primary trimethylaminuria syndrome: more than an unpleasant odor. Int J Dermatol 2023; 62: e176–8). At present, over 40 variants in FMO3 associated with TMAU have been identified. Secondary or acquired TMAU is the result of a combination of factors including increased consumption of dietary precursors, gut dysbiosis, hepatic impairment and hormonal fluctuations resulting in an accumulation of TMA. Treatment regimens involve limiting precursors intake, using acidic soaps to reduce the volatility of excreted TMA, targeting gut microbiota, and the use of oral sequestering agents (Schmidt AC, Leroux JC. Treatments of trimethylaminuria: where we are and where we might be heading. Drug Discov Today 2020; 25: 1710–17). However, current treatment options have had limited therapeutic effect. Referral to metabolic specialists for correct nutritional support and referral to psychiatry is paramount for these patients. As evident from our patient’s viewpoint, this diagnosis can have a lifelong impact on social engagement and psychological health.

Abstract Background/Aims Hypophosphatasia (HPP) is an ultra-rare genetic disorder characterised by low activity of tissue non-specific alkaline phosphatase (TNAP). Due to heterogeneity of clinical presentation and lack of definitive biochemical testing, misdiagnosis and diagnostic delay are common. Methods We used information reported by HPP patients to the Rare and Undiagnosed Diseases Study (RUDY) online registry (www.rudystudy.org). We included patients with a self-reported diagnosis of HPP and information on at least one of our outcomes. We described their diagnostic journey, including diagnostic delays, initial symptoms, incorrect diagnoses and healthcare professionals seen. Results 16 participants with a self-reported diagnosis of HPP were included in the analysis with 14/16 female. Of those reporting the date of initial symptom onset, 9/14 participants had symptom onset before the age of 18, whereas five had symptom onset in adulthood. The median time from symptom onset to HPP final diagnosis was 26.5 years (N = 8, IQR 11.2 to 34.6). From the first GP visit related HPP to final diagnosis the median time was 9.5 years (N = 6, IQR 6.2 to 11.1), and from the first hospital visit related to HPP, the median time to final diagnosis was 3.9 years (N = 10, IQR 0.8 to 10.5). Among participants reporting initial symptoms (N = 13), 16 categories of initial symptom were reported, with a median of two initial symptom categories per participant (IQR 1 to 2). The most prevalent initial symptom was pain (10/13, 77%). Of these 10 participants, four had lower limb pain, one had upper limb pain, one had back pain, and five had pain of unspecified location. Skeletal deformity at birth, dental manifestations, joint swelling, and infantile feeding problems were each present in 2/13 participants (15%). Among participants reporting whether they had received other diagnoses prior to that of HPP (N = 13), nine participants (75%) received at least one other diagnosis, with diagnoses of 10 different conditions reported across the cohort. The most common other diagnosis was fibromyalgia (4/13, 31%), followed by hypermobility (2/13, 15%). 21 different types of healthcare professionals were seen prior to final diagnosis. General Practitioners were the most commonly consulted (9/14, 64%). This was followed by allied health professionals (8/14, 57%). Of the eight participants seeing allied health professionals, all eight saw physiotherapists, and 4 (29% of total) also saw at least one other allied health professional. Other types of healthcare professional seen by multiple responders included orthopaedic surgeons (5/14, 36%), rheumatologists (5/14, 36%), geneticists (4/14, 29%), endocrinologists (3/14, 21%), metabolic specialists (3/14, 21%) and dentists (2/14, 14%). Conclusion Patients typically present with a cluster of symptoms, often including pain, and are often seen by general practitioners and physiotherapists before diagnosis. Increasing awareness of HPP in these professions may improve early recognition of the disease. Disclosure D. Marsden: None. R. Ridley: None.

Consensus guidelines for the diagnosis and management of succinic semialdehyde dehydrogenase deficiency

This review article initiates a series focused on metabolic medicine, a field that has yet to receive adequate attention within the domestic medical education system. The primary aim of this series is to demonstrate the prospects in understanding metabolic diseases and contemporary treatment modalities, with particular emphasis on those intersecting with endocrinology. The review defines metabolic medicine, explores its historical evolution, and outlines its principal trajectories. It also addresses the specialization within metabolic medicine, discussing the potential benefits this knowledge holds for various medical specialists. Furthermore, the article examines the treatment methodologies for prevalent and socially significant conditions, such as obesity and type 2 diabetes mellitus, through the lens of metabolic medicine. It underscores the pivotal role of metabolic specialists in patient management with metabolic syndrome, a common precursor to diabetes mellitus and cardiovascular diseases if not corrected in a timely manner. Emphasis is placed on reviewing bariatric surgical interventions, with a critical comparison of their efficacy and potential side effects. Additionally, the article highlights the critical role of metabolic medicine specialists in the management of patients who have undergone bariatric surgery. KEYWORDS: metabolic medicine, metabolologist, nutritionist, diabetes mellitus, obesity, metabolic syndrome, metabolism, nutritional support, parenteral nutrition. FOR CITATION: Dreval A.V., Nechaeva O.A., Dreval O.A., Britvin T.A., Gabrielyan A.R. Metabolic medicine. Russian Medical Inquiry. 2024;8(9):518–525 (in Russ.). DOI: 10.32364/2587-6821-2024-8-9-3

» Bone health optimization (BHO) has become an increasingly important consideration in orthopaedic surgery because deterioration of bone tissue and low bone density are associated with poor outcomes after orthopaedic surgeries.» Management of patients with compromised bone health requires numerous healthcare professionals including orthopaedic surgeons, primary care physicians, nutritionists, and metabolic bone specialists in endocrinology, rheumatology, or obstetrics and gynecology. Therefore, achieving optimal bone health before orthopaedic surgery necessitates a collaborative and synchronized effort among healthcare professionals.» Patients with poor bone health are often asymptomatic and may present to the orthopaedic surgeon for reasons other than poor bone health. Therefore, it is imperative to recognize risk factors such as old age, female sex, and low body mass index, which predispose to decreased bone density.» Workup of suspected poor bone health entails bone density evaluation. For patients without dual-energy x-ray absorptiometry (DXA) scan results within the past 2 years, perform DXA scan in all women aged 65 years and older, all men aged 70 years and older, and women younger than 65 years or men younger than 70 years with concurrent risk factors for poor bone health. All women and men presenting with a fracture secondary to low-energy trauma should receive DXA scan and bone health workup; for fractures secondary to high-energy trauma, perform DXA scan and further workup in women aged 65 years and older and men aged 70 years and older.» Failure to recognize and treat poor bone health can result in poor surgical outcomes including implant failure, periprosthetic infection, and nonunion after fracture fixation. However, collaborative healthcare teams can create personalized care plans involving nutritional supplements, antiresorptive or anabolic treatment, and weight-bearing exercise programs, resulting in BHO before surgery. Ultimately, this coordinated approach can enhance the success rate of surgical interventions, minimize complications, and improve patients' overall quality of life.

A 4-year-old boy presented in the neurologic clinic with delayed psychomotor development and progressive neurologic symptoms that started from the age of 20 months. Physical examination revealed ataxic features and a global development delay. The MRI was significant for hypomyelination. The most common causes of leukodystrophy were rolled out. He was referred to an inherited metabolic disease specialist under suspect of inborn metabolic errors because of laboratory analysis, which showed elevated levels of lactic acid, pyruvate, 4-Hydroxy-Phenylactic acid, 3-Hydroxy propionic acid, and decreased levels of PCO2, HCO3, total CO2, 25-Hydroxyvitamin D. These results were unspecific and mitochondrial disease was highly suspected. However, the genetic study was requested to get a defined diagnosis and treatment; the whole exon sequencing result showed a homozygous variant of uncertain significance mutation; related to an amino acid change from Ile to Thr at position 1002 in the POLR3B gene, which helped us to reveal the final diagnosis, and the genetic counseling were recommended for the next pregnancies. POLR3-related Leukodystrophy is a very rare disease. The early diagnosis should be raised depending on clinical history and MRI findings after other conditions were rolled out, and the confirmed diagnosis depends on the genetic study.