NOTCH3 Variants in Patients with Suspected CADASIL

Background: Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease. It is clinically, radiologically, and genetically heterogeneous and is caused by NOTCH3 mutations. Methods: In this study, we analyzed NOTCH3 in 368 patients with suspected CADASIL using next-generation sequencing. The significant variants detected were reported along with the clinical and radiological features of the patients. Results: Heterozygous NOTCH3 changes, mostly missense mutations, were detected in 44 of the 368 patients (12%). Conclusions: In this single-center study conducted on a large patient group, 30 different variants were detected, 17 of which were novel. CADASIL, which can result in mortality, has a heterogeneous phenotype among individuals in terms of clinical, demographic, and radiological findings regardless of the NOTCH3 variant

Lathosterolosis: a rare cholesterol metabolism disorder with a wide range of clinical variability

Objectives: Lathosterolosis is a rare autosomal recessive congenital disease that occurs due to homozygous or compound heterozygous mutations in the sterol C5-desaturase (SC5D) gene. We report a male patient with biallelic missense variant detected in the SC5D gene.Case presentation: An eight-month-old male patient was referred to the department of paediatric neurology for status epilepticus. He had no remarkable dysmorphic features except micrognathia, ptotic ear and thin-stranded hair. Laboratory tests revealed an alanine aminotransferase level of 502 IU/L and an aspartate aminotransferase level of 279 IU/L; other biochemical test results were normal. The brain MRI revealed atrophic changes in both hemispheres. A decrease in the volume of brain stem and thin corpus callosum were noticeable. Whole exome sequencing was performed because of consanguineous marriage and sibling death in his medical history, and the encountered features were consistent with suspected neurometabolic disease in the cranial imaging and the presence of borderline psychomotor retardation. A biallelic missense variant, c.656T > C p.(Leu219Ser), was identified in the SC5D gene.Conclusions: Lathosterolosis is a rare cholesterol metabolism disorder and can be presented with a wide range of clinical features by newly reported cases. Lathosterolosis should be considered in cases with cataracts, delayed neuromotor developmental milestones and high levels of live

Two Patients with Resistance to Thyroid Hormones

WOS: 000384166801608..

Two Patients with Resistance to Thyroid Hormones

WOS: 000384166801608

Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients

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