Heavy Metal and Trace Element Status and Dietary Determinants in Children with Phenylketonuria.

Background/Objectives: Heavy metals are a group of metals and metalloids that have a relatively high density. They can cause toxicity even at very low levels. Trace elements are required by all living organisms to maintain their normal growth, metabolism, and development. Oral intake is the main route of exposure to both heavy metals and trace elements. Phenylketonuria (PKU) is the most common amino acid metabolic disorder, and the best known treatment for patients requiring treatment is a phenylalanine (Phe)-restricted diet. The objective of the present study was to evaluate the plasma heavy metal levels, sources of exposure, changes in these levels according to dietary regimen, and trace element levels and their correlations with heavy metals in PKU patients. Methods: The study was conducted between July 2022 and January 2024 on 105 patients aged 2-6 years diagnosed with PKU. Results: The percentage of Pb levels in individuals in the upper quartile increased by 3.47 times (95% CI = 1.07-11.29) in those who consumed canned foods and 7.29 times (95% CI = 1.21-44.03) in those who consumed spring water. The percentage of As levels in the upper tertile increased by a factor of 7.26 (95% CI = 2.09-25.28) in individuals under four years of age and 8.17 times (95% CI = 2.13-31.27) in canned food users. The odds of having blood Cd levels in the upper tertile were 0.09 (95% CI = 0.01-0.96) for those being breastfed for 6-11 months compared to 0-5 months. Zn levels were lower (93.0 vs. 83.6 µg/dL, p = 0.008) in patients on a Phe-restricted diet. Conclusions: The present study did not find a relationship between heavy metal exposure and the dietary treatment status of patients with PKU. Our findings indicate that canned food consumption is a significant contributing factor to heavy metal exposure in PKU patients. Furthermore, our findings revealed a relationship between age, perception of economic level, breastfeeding, kitchen equipment, and water usage and the levels of certain heavy metals.

Evaluation of Exposure to Bisphenol A, Bisphenol F, and Phthalates in Patients with Phenylketonuria and Its Differences According to Dietary Status.

BACKGROUND: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. METHODS: In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2-6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. RESULTS: Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09-10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09-166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06-8.60). CONCLUSION: Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure.

Dihydropyrimidinase deficiency with atrioventricular septal defect: a case report.

OBJECTIVES: Dihydropyrimidinase deficiency is a rare autosomal recessive disorder of the pyrimidine degradation pathway, with fewer than 40 patients published. Clinical findings are variable and some patients may remain asymptomatic. Global developmental delay and increased susceptibility to 5-fluorouracil are commonly reported. Here we present atrioventricular septal defect as a novel feature in dihydropyrimidinase deficiency. CASE PRESENTATION: A four-year-old male with global developmental delay, dysmorphic facies, autistic features and a history of seizures was diagnosed with dihydropyrimidinase deficiency based on strikingly elevated urinary dihydrouracil and dihydrothymine and a homozygous pathogenic nonsense variant in DPYS gene. He had a history of complete atrioventricular septal defect corrected surgically in infancy. CONCLUSIONS: This is the second report of congenital heart disease in dihydropyrimidinase deficiency, following a single patient with a ventricular septal defect. The rarity of the disease and the variability of the reported findings make it difficult to describe a disease-specific clinical phenotype. The mechanism of neurological and other systemic findings is unclear. Dihydropyrimidinase deficiency should be considered in patients with microcephaly, developmental delay, epilepsy and autistic traits. We suggest that congenital heart disease may also be a rare phenotypic feature.

Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency.

The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient registry of the International Working Group on Neurotransmitter related Disorders (iNTD) were studied with in silico analyses, pathogenicity scores and molecular modeling of ALDH5A1 variants. Leading initial symptoms, with onset in infancy, were developmental delay and hypotonia. Year of birth and specific initial symptoms influenced the diagnostic delay. Clinical phenotype of 26 individuals (median 12 years, range 1.8-33.4 years) showed a diversifying course in follow-up: 77% behavioral problems, 76% coordination problems, 73% speech disorders, 58% epileptic seizures and 40% movement disorders. After ataxia, dystonia (19%), chorea (11%) and hypokinesia (15%) were the most frequent movement disorders. Involvement of the dentate nucleus in brain imaging was observed together with movement disorders or coordination problems. Short attention span (78.6%) and distractibility (71.4%) were the most frequently behavior traits mentioned by parents while impulsiveness, problems communicating wishes or needs and compulsive behavior were addressed as strongly interfering with family life. Treatment was mainly aimed to control epileptic seizures and psychiatric symptoms. Four new pathogenic variants were identified. In silico scoring system, protein activity and pathogenicity score revealed a high correlation. A genotype/phenotype correlation was not observed, even in siblings. This study presents the diversifying characteristics of disease phenotype during the disease course, highlighting movement disorders, widens the knowledge on the genotypic spectrum of SSADHD and emphasizes a reliable application of in silico approaches.

Electro-clinical features and long-term outcomes in guanidinoacetate methyltransferase (GAMT) deficiency.

OBJECTIVE: To evaluate clinical characteristics and long-term outcomes in patients with guanidinoacetate methyltransferase (GAMT) deficiency with a special emphasis on seizures and electroencephalography (EEG) findings. METHODS: We retrospectively analyzed the clinical and molecular characteristics, seizure types, EEG findings, neuroimaging features, clinical severity scores, and treatment outcomes in six patients diagnosed with GAMT deficiency. RESULTS: Median age at presentation and diagnosis were 11.5 months (8-12 months) and 63 months (18 months -11 years), respectively. Median duration of follow-up was 14 years. Global developmental delay (6/6) and seizures (5/6) were the most common symptoms. Four patients presented with febrile seizures. The age at seizure-onset ranged between 8 months and 4 years. Most common seizure types were generalized tonic seizures (n = 4) and motor seizures resulting in drop attacks (n = 3). Slow background activity (n = 5) and generalized irregular sharp and slow waves (n = 3) were the most common EEG findings. Burst-suppression and electrical status epilepticus during slow-wave sleep (ESES) pattern was present in one patient. Three of six patients had drug-resistant epilepsy. Post-treatment clinical severity scores showed improvement regarding movement disorders and epilepsy. All patients were seizure-free in the follow-up. CONCLUSIONS: Epilepsy is one of the main symptoms in GAMT deficiency with various seizure types and non-specific EEG findings. Early diagnosis and initiation of treatment are crucial for better seizure and cognitive outcomes. This long-term follow up study highlights to include cerebral creatine deficiency syndromes in the differential diagnosis of patients with global developmental delay and epilepsy and describes the course under treatment.

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

Coexistence of Two Rare Conditions Complicating the Other's Management: Propionic Acidemia and Apert Syndrome.

Introduction: Propionic acidemia (PA) is an inborn error of organic acid metabolism inherited in an autosomal recessive manner. The neonatal-onset disease may present with feeding difficulties and vomiting; seizures, coma, and death may occur if untreated. In addition, catabolic processes such as infections and surgical procedures could cause metabolic decompensation, so patients with organic acidemia should be followed closely. Case Presentation: Here, a patient diagnosed with PA and Apert syndrome in the neonatal period and the complications caused by the coexistence of the two entities are mentioned. The difficulties precipitated by the coexistence of Apert syndrome and PA make this case unique. She has had prolonged hospitalizations due to metabolic decompensations after cranioplasty and inguinal hernia repair, both triggered by nosocomial respiratory infections, complicating both the surgical treatment of Apert syndrome and the management of PA. Conclusion: Coexistence of these two serious disorders mandates a more prudent clinical management as Apert syndrome patients undergo several surgical procedures, rendering them susceptible to catabolic decompensations.

Long-term clinical evaluation of patients with alpha-mannosidosis - A multicenter study.

BACKGROUND: Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the MAN2B1 gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly. This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics. METHOD: Sixteen patients diagnosed with alpha-mannosidosis who presented to four pediatric metabolic units were included in the study. The patients' medical records were analyzed and data on demographics, clinical presentation and laboratory findings were recorded. RESULTS: Of the 16 patients (6 females, 10 males) with alpha mannosidosis included in the study, the mean age at the time of diagnosis was 79.4 ± 56.1 (16-208) months, and the mean diagnosis delay time was 57.9 ± 51.9 (4-181) months. Hearing loss was the primary manifestation found in seven out of 16 patients (43.8%), followed by speech delay in 37.8%. On clinical follow-up, 87.5% of patients experienced recurrent infections, mainly in the upper respiratory tract, with 12 requiring the use of a hearing aid. Hepatomegaly was found in six out of 13 patients who received abdominal ultrasonography; two out of 12 patients who underwent echocardiography were found to have mitral valve prolapse (16.6%). Upon neurological evaluation, five patients displayed no neurological manifestation. Delayed language development was observed in nine (56.3%) patients, intellectual disability in eight (50%) patients, and hypertonicity was identified in one (6.3%) patient with the severe form of the disease. Homozygous c.2477C>A (p.Ser826Ter) and homozygous c.967G>A (p.Glu323Lys) novel variants were detected in four patients and one patient, respectively. The most common variant observed in the study was c.2477C>A (p.Ser826Ter). CONCLUSION: The present study identified two novel MAN2B1 variants. An evaluation of the long-term outcome of alpha-mannosidosis, in which the early initiation of enzyme replacement therapy (ERT) may lead to a better clinical outcome, can permit a better analysis of the effect of ERT on the natural progression of the disease.

Adult-onset carnitine palmitoyl transferase II (CPT II) deficiency presenting with rhabdomyolysis and acute kidney injury.

Metabolic myopathies are among the treatable causes of rhabdomyolysis and myoglobinuria. Carnitine palmitoyl transferase 2 (CPT II) deficiency is one of the most common causes of recurrent myoglobinuria in adults. It is an inherited disorder of fatty acid oxidation pathway, commonly associated with elevated acylcarnitine levels. In this case report, we present a 49-year-old male patient who developed acute kidney injury after rhabdomyolysis and was thus diagnosed with CPT2 deficiency after his first episode of rhabdomyolysis. Inborn errors of metabolism should be kept in mind in patients with rhabdomyolysis. Acylcarnitine profile may be normal in CPT II deficiency, even during an acute attack, and molecular genetic diagnostics should be applied if there is high index of clinical suspicion.

Validity and reliability of the MetabQoL 1.0 and assessment of neuropsychiatric burden in organic acidemias: Reflections from Turkey.

OBJECTIVES: The MetabQoL 1.0 is the first disease-specific health related quality of life (HrQoL) questionnaire for patients with intoxication-type inherited metabolic disorders. Our aim was to assess the validity and reliability of the MetabQoL 1.0, and to investigate neuropsychiatric burden in our patient population. METHODS: Data from 29 patients followed at a single center, aged between 8 and 18 years with the diagnosis of methylmalonic acidemia (MMA), propionic acidemia (PA) or isovaleric acidemia (IVA), and their parents were included. The Pediatric Quality of Life Inventory (PedsQoL) was used to evaluate the validity and reliability of MetabQoL 1.0. RESULTS: The MetabQoL 1.0 was shown to be valid and reliable (Cronbach's alpha: 0.64-0.9). Fourteen out of the 22 patients (63.6%) formally evaluated had neurological findings. Of note, 17 out of 20 patients (85%) had a psychiatric disorder when evaluated formally by a child and adolescent psychiatrist. The median mental scores of the MetabQoL 1.0 proxy report were significantly higher than those of the self report (p = 0.023). Patients with neonatal-onset disease had higher MetabQoL 1.0 proxy physical (p = 0.008), mental (p = 0.042), total scores (p = 0.022); and self report social (p = 0.007) and total scores (p = 0.043) than those with later onset disease. CONCLUSIONS: This study continues to prove that the MetabQoL 1.0 is an effective tool to measure what matters in intoxication-type inherited metabolic disorders. Our results highlight the importance of clinical assessment complemented by patient reported outcomes which further expands the evaluation toolbox of inherited metabolic diseases.

Predictors of eventual requirement of phenylalanine-restricted diet in young infants with phenylalanine hydroxylase deficiency initially managed with sapropterin monotherapy.

BACKGROUND: Phenylalanine (Phe)-restricted diet is associated with lower quality of life for patients with phenylketonuria (PKU), and a concern for caregivers of recently-diagnosed infants. Sapropterin is an oral drug used as an alternative or adjunct to dietary treatment. We have observed that some of the young infants initially managed successfully with sapropterin monotherapy have required dietary treatment in long-term follow-up. We aimed to determine the baseline factors associated with future initiation of dietary treatment in these patients. METHODS: Data were obtained retrospectively from the medical records of 80 PKU patients started on sapropterin monotherapy before 3 months of age between 2011 and 2021. RESULTS: The patients were followed for a median of 3.9 years (Q1-Q3: 2.5-5.75 years). Sapropterin was tapered down and discontinued in 5 patients (6.3%) as their Phe levels remained below 360 µmol/L without treatment. Sapropterin monotherapy was sufficient in 62 patients (77.5%), while 13 (16.2%) required dietary treatment. Phe and tyrosine (Tyr) levels, and Phe:Tyr ratios differed significantly among the patients maintained on sapropterin monotherapy and those started on dietary treatment, but the Phe:Tyr ratio at diagnosis was the most important independent baseline variable (OR: 1.61, 95% CI: 1.15-2.27, p = 0.006), with Phe:Tyr ratio at diagnosis >5.25 associated with dietary treatment (sensitivity: 90.0%, specificity: 81.8%). Genotypic phenotype value (GPV), unavailable at baseline, was also associated with dietary treatment (median GPV 9.2 vs. 3.8, p = 0.006), but some genotypes were not specific to the final treatment modality. DISCUSSION: We propose that the Phe:Tyr ratio at diagnosis is an important indicator to predict dietary requirement in young infants initially managed with sapropterin monotherapy.

Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism.

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.

COVID-19 in inherited metabolic disorders: Clinical features and risk factors for disease severity.

BACKGROUND: Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center. METHODS: Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD. RESULTS: Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults. DISCUSSION: This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.

Successful management of rhabdomyolysis with triheptanoin in a child with severe long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency.

Early-onset long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a fatty acid ß-oxidation disorder with a poor prognosis. Triheptanoin, an anaplerotic oil with odd-chain fatty acids can improve the disease course. The female patient presented here was diagnosed at the age of 4 months, and treatment was started as fat restriction, frequent feeding, and standard medium-chain triglyceride supplementation. In follow-up, she had frequent rhabdomyolysis episodes (∼8 per year). At the age of six, she had 13 episodes in 6 months, and triheptanoin was started as part of a compassionate use program. Following unrelated hospital stays due to multisystem inflammatory syndrome in children and a bloodstream infection, she had only 3 rhabdomyolysis episodes, and hospitalized days decreased from 73 to 11 during her first year with triheptanoin. Triheptanoin drastically decreased the frequency and severity of rhabdomyolysis, but progression of retinopathy was not altered.

Splenic Gaucheroma Leading to Incidental Diagnosis of Gaucher Disease in a 46-Year-Old Man with a Rare GBA Mutation: A Case Report.

BACKGROUND: Gaucher disease is a common lysosomal storage disease caused by the deficiency of the ß-glucosidase enzyme, leading to sphingolipid accumulation in the reticuloendothelial system in Gaucher cells. Clinical findings are quite variable and some patients may remain asymptomatic lifelong. However, even when patients have mild symptoms, there is a significant increase in their quality of life with enzyme replacement therapy. We aimed to reveal the relationship between a rare mutation in the Glucosylceramidase Beta (GBA) gene and clinical signs and symptoms. Another aim of the study was to show the effect of enzyme replacement therapy on the quality of life, even in patients with mild symptoms. CASE PRESENTATION: Here, we report a 46-year-old male diagnosed with Gaucher disease based on splenic Gaucheromas incidentally discovered in a cardiac computerized tomography scan. In GBA gene analysis, the extremely rare R87W mutation was detected in a homozygous state. In retrospect, the patient had nonspecific symptoms such as fatigue and bone pain for a long time, which were substantially ameliorated by enzyme replacement therapy. CONCLUSION: In patients with adult-onset Gaucher disease, the symptoms may be mild, causing significant diagnostic delay. Gaucher disease may be included in the differential diagnosis of abdominal malignancies. Early diagnosis and treatment can improve quality of life and prevent unnecessary procedures.