Autosomal Recessive Condition Research Articles

#2633 Navigating complexity: a case report of chronic kidney disease with renal stone unravelling a rare metabolic disorder

Abstract Clinical Presentation A 48-year-old female of Asian heritage was referred for renal assessment after experiencing recurrent acute kidney injury (AKI) with incomplete recovery between episodes. This was initially attributed to dehydration and interstitial nephritis stemming from long-standing vomiting, a manifestation of gastroscopy-proven erosive gastritis, compounded by the use of high-dose proton pump inhibitors (PPI). Her relevant medical history is of right nephrectomy in 1996 due to recurrent urinary tract infections (UTIs), and previous left renal calculus in 2019 with no visible stones on further CT imaging. Despite living with a single kidney, her baseline eGFR had been normal prior to referral. While unaware of her mother's medical history, her father was recently diagnosed with kidney disease (no clear history) and her sister Wilson's disease. A kidney biopsy was undertaken given the incomplete eGFR recovery between episodes. The biopsy revealed adequate tissue including 24 glomeruli, no significant glomerular pathology was seen. There is 65% tubulointerstitial atrophy and fibrosis, and yellow to red-brown-tinged crystals within tubular lumina and epithelial cells, prompting a histiocytic reaction. These crystals were birefringent under polarized light and did not stain with Perl's and Von Kossa stain (Fig. 1a-d). Immunofluorescence was negative for all immunoglobulins and complement fractions. No immune complex/substructure deposits were seen in the glomeruli on electron microscopy. Blood tests assessing APRT activity indicated values within the carrier range (Table 1). The patient and her family have been referred for a comprehensive genetic testing for APRT genetic mutations. Treatment with Allopurinol 300 mg daily resulted in a sustained eGFR improvement from 19 to 33 ml/min/1.73m2 at 6 months after initiation (Fig. 1). Discussion Adenine phosphoribosyl transferase (APRT) deficiency, also known as Dihydroxyadenineuria, is a rare autosomal recessive inherited condition leading to kidney stones. If left untreated, up to 25% progress to end-stage kidney disease (ESKD). Although inherited, half of patient present in adulthood and may do so with laboratory findings of CKD rather than specifically with stones [1]. This case highlights the significance of precise diagnosis in calculi-related kidney diseases. Early intervention can alter the trajectory of specific conditions, averting progression to ESKD. This case is unusual in being a carrier of an autosomal recessive condition presenting with full manifestations of the disease. Patient Consent The patient has given verbal, documented consent for case publication. Acknowledgment We thank all renal and pathology staff members at Salford Care Organisation who contributed to the diagnosis and management of our case.

#1556 An unusually high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russia

Abstract Background and Aims A hypomorphic TMEM67 variant c.1843T>C (p.Cys615Arg) (rs201893408) is associated with an autosomal-recessive condition characterized by a combination of nephronophthisis and liver fibrosis, and, in some cases, neurologic manifestations. According to the gnomAD database, it reaches the highest prevalence in Swedish population (MAF=17/26128, 0.00065). In two large European studies of nephronophthisis and related conditions, the contribution of this pathogenic allele to TMEM67-associated disorders reached 15%-27%. The report presents the first evidence for the major contribution of this recurrent variant to nephronophthisis in Russia. Method Blood DNA samples of 29 pediatric patients, undergoing chronic renal replacement therapy in a dialysis department of a large pediatric medical center, were evaluated by targeted (“clinical exome”) sequencing. KAPA HyperCap Heredity Panel (Roche) was used for target enrichment. Sequencing was performed on Illumina Nextseq2000 device. The alignment on GRCh37 reference genome sequence was made using BWA 0.7.12; HaplotypeCaller (GATK 3.3.0) was used for variant calling. Causative variants were verified by Sanger sequencing. Results Among other findings, we have identified two unrelated Russian patients, homozygous for TMEM67 p.Cys615Arg mutation; none of them have previously been diagnosed with nephronophthisis. Patient D, a 11-year-old girl, presented with unexplained chronic kidney disease with unremarkable ultrasound findings. Patient B was an 8-year-old girl with chronic kidney disease linked to bilateral ureterohydronephrosis. In both patients, cholestatic hepatitis of unknown etiology was diagnosed. No neurological involvement was reported. The parents of both girls denied consanguinity. One more Russian patient homozygous for p.Cys615Arg variant had been previously described [Andreeva and Savenkova, 2022; in Russian]: the 2-year-old child born from non-consanguineous parents had prenatally identified multiple renal cysts, nephrogenic arterial hypertension, and laboratory signs of cholestasis. The analysis of Ruseq database (ruseq.ru) confirmed high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russian population (MAF=14/10860, 0.0013). Conclusion TMEM67 c.1843T>C (p.Cys615Arg) allele is particularly common in Russian pediatric patients with chronic kidney disease and liver involvement, and, therefore, deserves to be analyzed in other countries with predominantly Slavic population.

The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients.

Carpenter syndrome (CRPTS) is a rare autosomal recessive condition caused by biallelic variants in genes that encode negative regulators of hedgehog signalling (RAB23 [CRPT1] or, more rarely, MEGF8 [CRPT2]), and is characterised by craniosynostosis, polysyndactyly, and other congenital abnormalities. We describe a further six families comprising eight individuals with MEGF8-associated CRPT2, increasing the total number of reported cases to fifteen, and refine the phenotype of CRPT2 compared to CRPT1. The core features of craniosynostosis, polysyndactyly and (in males) cryptorchidism are almost universal in both CRPT1 and CRPT2. However, laterality defects are present in nearly half of those with MEGF8-associated CRPT2, but are rare in RAB23-associated CRPT1. Craniosynostosis in CRPT2 commonly involves a single midline suture in comparison to the multi-suture craniosynostosis characteristic of CRPT1. No patient to date has carried two MEGF8 gene alterations that are both predicted to lead to complete loss-of-function, suggesting that a variable degree of residual MEGF8 activity may be essential for viability and potentially contributing to variable phenotypic severity. These data refine the phenotypic spectrum of CRPT2 in comparison to CRPT1 and more than double the number of likely pathogenic MEGF8 variants in this rare disorder.

AAV-mediated expression of mouse or human GLDC normalises metabolic biomarkers in a GLDC-deficient mouse model of Non-Ketotic Hyperglycinemia

Non-Ketotic Hyperglycinemia (NKH) is a rare inborn error of metabolism caused by impaired function of the glycine cleavage system (GCS) and characterised by accumulation of glycine in body fluids and tissues. NKH is an autosomal recessive condition and the majority of affected individuals carry mutations in GLDC (glycine decarboxylase). Current treatments for NKH have limited effect and are not curative. As a monogenic condition with known genetic causation, NKH is potentially amenable to gene therapy. An AAV9-based expression vector was designed to target sites of GCS activity. Using a ubiquitous promoter to drive expression of a GFP reporter, transduction of liver and brain was confirmed following intra-venous and/or intra-cerebroventricular administration to neonatal mice. Using the same capsid and promoter with transgenes to express mouse or human GLDC, vectors were then tested in GLDC-deficient mice that provide a model of NKH. GLDC-deficient mice exhibited elevated plasma glycine concentration and accumulation of glycine in liver and brain tissues as previously observed. Moreover, the folate profile indicated suppression of folate one‑carbon metabolism (FOCM) in brain tissue, as found at embryonic stages, and reduced abundance of FOCM metabolites including betaine and choline. Neonatal administration of vector achieved reinstatement of GLDC mRNA and protein expression in GLDC-deficient mice. Treated GLDC-deficient mice showed significant lowering of plasma glycine, confirming functionality of vector expressed protein. AAV9-GLDC treatment also led to lowering of brain tissue glycine, and normalisation of the folate profile indicating restoration of glycine-derived one‑carbon supply. These findings support the hypothesis that AAV-mediated gene therapy may offer potential in treatment of NKH.

Expanded targeted preconception screening panel in Israel: findings and insights

BackgroundWe aimed to analyse the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP), beyond the first-tier test covered by the Israeli Ministry of Health (IMOH)...

Congenital chloride diarrhoea in a Chinese infant with a compound heterozygous SLC26A3 mutation

IntroductionCongenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations.Case presentationA 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency.ConclusionsCCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

Whole exome sequencing combined with in silico protein analysis identifies rare truncating variants in the TYR gene associated with oculocutaneous albinism1A (OCA1A) in an Iranian patient

Oculocutaneous albinism type 1A (OCA1A) is an autosomal recessive tyrosinase-negative condition caused by deleterious variants in the TYR gene. Using whole exome sequencing (WES) followed by Sanger sequencing, we detected rare pathogenic variants (c.286dupA and c.763C > T) within the TYR gene in a 12-year-old Iranian female who met the clinical criteria proposed for OCA. Through comprehensive in silico protein analysis, we elucidated the functional impact of these two variants. c.286dupA induced a frameshift, leading to the loss of the entire copper-binding tyrosinase domain and the only transmembrane melanosome-bound tyrosinase helix. Similarly, c.763C > T introduced a premature stop codon, resulting in the loss of approximately two-thirds of the copper-binding tyrosinase domain and the transmembrane helix. These findings signified a substantial disturbance in the normal function of tyrosinase. Our study presents the first report of co-occurring pathogenic c.286dupA and c.763C > T variants, comprehensively investigating their functional impact using in-silico protein tools.

Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy)

Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in B4GALT7 gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region. B4GALT7 encodes galactosyltransferase I, one of the enzymes involved in the biosynthesis of the linker region. Conditions caused by pathogenic biallelic variants in genes implicated in the synthesis of the tetrasaccharide linker of PG are known as linkeropathies.Prenatal features are rarely described in this group of chondrodysplasias. We present a series of 12 unpublished patients having LRS and describe the perinatal phenotype. All the patients had a prenatal growth restriction with brevity of limbs. The other features revealed by ultrasounds were increased nuchal translucency at 10–12 weeks of gestation (50 %), feet abnormalities (clubfeet or metatarsus varus) (25 %), dislocation affecting at least one large joint (elbow, knee, wrist) (25 %). Bilateral bowing of femora was noted for two fetuses. Fibular hypertrophy was noted for one fetus. Prenatal helical computed tomography (CT) performed in three pregnancies showed additional data such as bowing of the forearm bones, proximal radio-ulnar synostosis, or dislocation of large joints. Prenatal sonographic and helical CT findings led to the prenatal diagnosis of LRS in four patients. We confirm that the neonatal clinical picture of LRS has an important overlap with that reported in patients with B4GALT7 deficiency outside La Réunion Island and other linkeropathies. The core of the phenotypic spectrum combines low birth height, micromelia, hypermobility, dislocation of at least one large joint, facial features with prominent eyes, microstomia, depressed nasal bridge, and midface hypoplasia. Other clinical features include clubfeet (33%), bifid thumb in one patient, and cardiac abnormalities in two patients. Radiological findings include radio-ulnar synostosis (75%), metaphyseal flaring, precocious carpal ossification, and a Swedish key appearance of the proximal femora. Finally, we also report radiological features rarely described in B4GALT7-linkeropathies, including bowing of the femora and fibular hypertrophy. Our results confirm the phenotypic continuum of LRS within linkeropathies with some additional findings, including a high frequency of clubfeet usually described in B3GALT6-linkeropathies, the presence of congenital heart diseases usually described in B3GAT3-linkeropathies, and a high frequency of metaphyseal flaring usually reported in B3GALT6 or XITLT1-linkeropathies.This is the first study that describes the perinatal phenotype in a cohort of patients with LRS. This study can help improve the prenatal diagnosis of the linkeropathies and add this group of conditions to the differential diagnosis of chondrodysplasias with multiple dislocations.In view of the founder effect for LRS in La Réunion Island, this disease should be suspected in fetuses with growth restriction and micromelia. Thus in case of LOH which include B4GALT7 identified in SNP-array, we recommend performing a targeted Sanger sequencing for the recurrent mutation c.808C > T; p. (Arg270Cys).

A rare case of hereditary ataxia: Gordon Holmes syndrome: a review of the literature

Gordon Holmes syndrome is an extremely rare, autosomal recessive condition with characteristic features of cerebellar progressive ataxia, cerebellar atrophy, and hypogonadotropic hypogonadism, which was first described in 1908 by the British neurologist of the same name. Two genes have to date been frequently associated with this syndrome, RNF216 and PNPLA61. A 23-year-old man presented with secondary sexual character deficiency and progressive difficulty in gait persisting for several years. He was eventually immobilized after seven years of ongoing symptoms and was definitively diagnosed with Gordon Holmes syndrome after genetic testing revealed RNF216 gene mutation.

Expanding Access to Noninvasive Prenatal Diagnosis for Monogenic Conditions to Consanguineous Families.

Cell-free fetal DNA exists within the maternal bloodstream during pregnancy and provides a means for noninvasive prenatal diagnosis (NIPD). Our accredited clinical service offers definitive NIPD for several autosomal recessive (AR) and X-linked conditions using relative haplotype dosage analysis (RHDO). RHDO involves next-generation sequencing (NGS) of thousands of common single nucleotide polymorphism (SNPs) surrounding the gene of interest in the parents and an affected or unaffected offspring to conduct haplotype phasing of the high- and low-risk alleles. NGS is carried out in parallel on the maternal cell-free DNA, and fetal inheritance is predicted using sensitive dosage calculations performed at sites where the parental genotypes differ. RHDO is not currently offered to consanguineous couples owing to the shared haplotype between parents. Here we test the expansion of RHDO for AR monogenic conditions to include consanguineous couples. The existing sequential probability ratio test analysis pipeline was modified to apply to SNPs where both parents are heterozygous for the same genotype. Quality control thresholds were developed using 33 nonconsanguineous cases. The performance of the adapted RHDO pipeline was tested on 8 consanguineous cases. The correct fetal genotype was predicted by our revised RHDO approach in all conclusive cases with known genotypes (n = 5). Haplotype block classification accuracies of 94.5% and 93.9% were obtained for the nonconsanguineous and consanguineous case cohorts, respectively. Our modified RHDO pipeline correctly predicts the genotype in fetuses from consanguineous families, allowing the potential to expand access to NIPD services for these families.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing(NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

An Overview of Reproductive Carrier Screening Panels for Autosomal Recessive and/or X-Linked Conditions: How Much Do We Know?

(Abstracted from Prenatal Diagnosis 2023;43:1416–1424 Reproductive carrier screening is designed to identify couples who are at a high risk of passing genetic disorders to their children. Advances in genetic screening technology have recently allowed for the commercial development and availability of genetic tests that can screen for autosomal recessive and X-linked genes for many disorders simultaneously.

Yield and Utility of Routine Epilepsy Panel Genetic Testing Among Young Patients With Seizures.

Objective: We examined the yield of routine epilepsy panel genetic testing in pediatric patients. Methods: We retrospectively reviewed epilepsy genetic panel results routinely performed in the hospital or clinic on patients <8 years old from July 2021 to July 2023. We evaluated demographics, family history, seizure type, severity, and frequency, development, tone and movement abnormalities, dysmorphism, and electroencephalography (EEG) or magnetic resonance imaging (MRI) results as predictors of results. Results: 65 patients were included with mean age 4.5 years. Sixty percent of patients were male; 11 patients had pathogenic variants (16.9%), 7 were carriers for autosomal recessive conditions (10.8%), 36 had variants of uncertain significance (55.4%), and 11 tested negative (16.9%). Pathogenic variants and variants of uncertain significance were unassociated with demographics, clinical features, imaging, or family history. Conclusion: Variants identified have potential implications for treatment (SCN1), comorbidity screening (TSC1), reproduction (ATAD1, PSAT1, and CLN8), and prognostication (FOXG1). Patients not routinely screened for a genetic cause of epilepsy by our standard practices had clinically relevant results.

ABCC2 p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation

BackgroundDubin-Johnson syndrome (DJS), a rare autosomal recessive liver condition, is caused by biallelic loss-of-function mutations of the ABCC2 gene. This study aimed to investigate genetic variations in the drug efflux...

Identification of novel mutations in TPK1 and SLC19A3 genes in families exhibiting thiamine metabolism dysfunction syndrome

Background and aimsThe occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders. Material and methodsThe selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative. ResultsThe first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene. ConclusionsCollectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.

Understanding the Variability of 22q11.2 Deletion Syndrome: The Role of Epigenetic Factors.

Initially described as a triad of immunodeficiency, congenital heart defects and hypoparathyroidism, 22q11.2 deletion syndrome (22q11.2DS) now encompasses a great amount of abnormalities involving different systems. Approximately 85% of patients share a 3 Mb 22q11.2 region of hemizygous deletion in which 46 protein-coding genes are included. However, the hemizygosity of the genes of this region cannot fully explain the clinical phenotype and the phenotypic variability observed among patients. Additional mutations in genes located outside the deleted region, leading to "dual diagnosis", have been described in 1% of patients. In some cases, the hemizygosity of the 22q11.2 region unmasks autosomal recessive conditions due to additional mutations on the non-deleted allele. Some of the deleted genes play a crucial role in gene expression regulation pathways, involving the whole genome. Typical miRNA expression patterns have been identified in 22q11.2DS, due to an alteration in miRNA biogenesis, affecting the expression of several target genes. Also, a methylation epi-signature in CpG islands differentiating patients from controls has been defined. Herein, we summarize the evidence on the genetic and epigenetic mechanisms implicated in the pathogenesis of the clinical manifestations of 22q11.2 DS. The review of the literature confirms the hypothesis that the 22q11.2DS phenotype results from a network of interactions between deleted protein-coding genes and altered epigenetic regulation.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis – A cross sectional study

ObjectivesCystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. MethodsA cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. Results64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. ConclusionIn this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. Clinical significanceClinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

Assessing the diagnostic utility of the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system using real-world data

BackgroundGaucher disease (GD) is a rare autosomal recessive condition associated with clinical features such as splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone abnormalities. Three clinical forms of GD have been defined based on the absence (type 1, GD1) or presence (types 2 and 3) of neurological signs. Early diagnosis can reduce the likelihood of severe, often irreversible complications. The aim of this study was to validate the ability of factors from the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system to discriminate between patients with GD1 and controls using real-world data from electronic patient medical records from Maccabi Healthcare Services, Israel’s second-largest state-mandated healthcare provider.MethodsWe applied the GED-C scoring system to 265 confirmed cases of GD and 3445 non-GD controls matched for year of birth, sex, and socioeconomic status identified from 1998 to 2022. The analyses were based on two databases: (1) all available data and (2) all data except free-text notes. Features from the GED-C scoring system applicable to GD1 were extracted for each individual. Patients and controls were compared for the proportion of the specific features and overall GED-C scores. Decision tree and random forest models were trained to identify the main features distinguishing GD from non-GD controls.ResultsThe GED-C scoring distinguished individuals with GD from controls using both databases. Decision tree models for the databases showed good accuracy (0.96 [95% CI 0.95–0.97] for Database 1; 0.95 [95% CI 0.94–0.96] for Database 2), high specificity (0.99 [95% CI 0.99–1]) for Database 1; 1.0 [95% CI 0.99–1] for Database 2), but relatively low sensitivity (0.53 [95% CI 0.46–0.59] for Database 1; 0.32 [95% CI 0.25–0.38]) for Database 2). The clinical features of splenomegaly, thrombocytopenia (< 50 × 109/L), and hyperferritinemia (300–1000 ng/mL) were found to be the three most accurate classifiers of GD in both databases.ConclusionIn this analysis of real-world patient data, certain individual features of the GED-C score discriminate more successfully between patients with GD and controls than the overall score. An enhanced diagnostic model may lead to earlier, reliable diagnoses of Gaucher disease, aiming to minimize the severe complications associated with this disease.

Pulmonary alveolar microlithiasis: A case report.

An uncommon autosomal recessive condition called pulmonary alveolar microlithiasis (PAM) is characterized by the buildup of intra-alveolar calcifications inside the lung parenchyma. In this case report, a 16-year-old female patient with PAM is examined in-depth clinically and radiologically. The patient's radiographs revealed dense consolidation in both lungs. The diagnosis of PAM was confirmed by high-resolution computed tomography (HRCT), which showed bilateral, extensive and symmetrical distribution of the calcifications. We go over PAM's clinical presentation, imaging traits, diagnostic difficulties, and current therapeutic strategies. In order to provide a complete overview of this uncommon lung illness, we also evaluate relevant research.

Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis

IntroductionCystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry...