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The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from the two index cases in Family 1 and 15 individuals were diagnosed from one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses  were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children., (© 2024 Wiley Periodicals LLC.)

Objectives: This study aimed to investigate the frequency and status of depression and anxiety among mothers of children with inborn errors of metabolism (IEM) who were on a restricted diet and previously experienced metabolic crises., Methods: This cross-sectional multicenter descriptive study included 93 children with IEM who were on restricted diet. The patients were divided into two groups: those who had experienced metabolic crises (n=44, urea cycle defect, organic acidemia, maple syrup urine disease, hereditary fructose intolerance) and those who had not experienced previous metabolic crises (n=49; phenylketonuria, galactosemia, and non-ketotic hyperglycinemia). The control group comprised 37 healthy children. The mothers of the patients and control participants answered a questionnaire about their and their children's demographic and clinical characteristics and completed the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T)., Results: The maternal BDI, STAI-S, and STAI-T scores were 6.3±5.2, 36.1±11.2, and 39.9±8.8, respectively, in the control group. The maternal BDI, STAI-S, and STAI-T scores of the children who had experienced (19.2±9.7; 44.0±12.4; 47.9±10.6) and those who had not experienced (13.9±9.1; 40.7 ±8.6; 45.3±8.3) a crisis were significantly higher than for the controls. The BDI score was significantly higher for the mothers of children who had experienced a crisis (p=0.011), whereas no significant difference was determined between the two patient groups regarding STAI-S and STAI-T scores. The mothers of four children who had experienced metabolic crises were on antidepressant therapy., Conclusion: Although their children were on a similar restricted diet, the mothers of children who previously experienced or who had the risk of experiencing metabolic crises had higher depression scores as compared with the mothers of children who did not experience a previous crisis. Early supportive therapy may be required for the families of these patients to lower the burden of stress., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients., Methods: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed., Results: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis ( n  = 1; 12.5%), interstitial lung disease ( n  = 1; 12.5%), and scleritis ( n  = 1; 12.5%), was also noted., Conclusion: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.

Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. In this cross-sectional, multicenter, descriptive study, medical records of 66 AKU patients were retrospectively evaluated. Patients' data regarding demographic, clinical and genetic characteristics were recorded. HGD database (http://hgddatabase.cvtisr.sk/) was used to identify HGD gene variants. Of the patients, 37 (56.1%) presented with isolated dark urine and 29 (43.9%) were diagnosed based on the clinical symptoms or family screening. One of these patients was on follow-up for 2 years due to Parkinsonism and was diagnosed with AKU on further analyses. Signs of ochronosis such as joint pain, low back pain and renal stones developed in childhood in 7 patients. Eight patients were diagnosed with depression via psychiatric evaluation. There were 14 (21.2%) patients operated on for ochronosis. The most frequent mutation observed in the patients was c.175delA, which was followed by c.674G > A and c.1007-2A > T mutations. Four novel mutations (c.189G > A, c.549+1G > T, c.1188+1G > A, and c.334 T > G) were identified in the patients included in the study. In addition to the known signs such as dark urine and skin pigmentation, symptoms involving different systems such as neurological findings and depression can also be encountered in AKU patients. The presence of a change in urine color needs to be questioned in patients presenting with different symptoms such as arthralgia/arthritis, renal stones or low-back pain, particularly in childhood, when skin ochronosis is not pronounced, and further examination should be performed., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)