A rare case of skeletal dysplasia: biallelic variant in ACAN gene.

OBJECTIVES: Spondylo-epimetaphyseal dysplasia-aggregan (SEMD-ACAN) is a rare form of osteo-chondrodysplasia that includes vertebral, epiphyseal and metaphyseal dysplasia. It occurs as a result of loss-of-function mutations in the ACAN gene, which encodes aggregan protein, which is the basic component of the extracellular matrix in cartilage. It results in disproportionately short stature and skeletal abnormalities. Here, we aimed to present the fourth SEMD-ACAN report in the literature. CASE PRESENTATION: A 9-year-old girl was admitted to our clinic with growth retardation. She was born from a first-degree cousin marriage with severe short stature (41 cm; -3.54 SDS). Her mother also had severe short stature. Her height was 110 cm (-4.6 SDS); she had midface hypoplasia, low-set ears, short neck, short limbs, and central obesity. Biochemical and hormonal tests were normal. Skeletal survey showed moderate platyspondylia, thoracolumbar scoliosis, lumbar lordosis, bilateral femoro-acetabular narrowing, and advanced bone age (10 years). The patient's brother was 100 cm (-3.97 SDS). He had similar but milder clinical findings. Biallelic ACAN variation (c.512C>T; p. Ala171Val) was detected in two siblings by next-generation sequencing. The parents were heterozygous carriers. Before, the heterozygous form of this variant has been reported in a 15-year-old boy with short stature, advanced bone age, and dysmorphic features. CONCLUSIONS: SEMD-ACAN is a rare genetic condition that affects bone growth and development and can cause physical and developmental abnormalities. This article highlights the importance of considering genetic testing in characteristic symptoms associated with SEMD-ACAN, such as severe growth retardation and skeletal abnormalities.

Evaluation of Serum Advanced Glycation End Product Levels and Microvascular Complications in Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVE: Advanced glycation end products (AGEs) are irreversible macromolecules formed by nonenzymatic reactions due to chronic hyperglycemia. The aim of this study was to assess the relationship between AGEs and the microvascular complications of children and adolescents with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Twenty-six T1DM patients with microvascular complications and 58 complication-naive patients who were similar regarding age, sex, and pubertal status enrolled in the study. Anthropometric, biochemical, ophthalmologic, and neurologic variables were compared with serum AGEs levels by the fluorescence method. RESULTS: There was no significant difference observed between the patients with complications and those without complications in terms of serum levels of AGEs and other biochemical parameters. However, the duration of T1DM and urine microalbumin-creatinine ratio (uACR) were significantly higher in the complication-positive group (P < .001). Serum levels of AGEs were found to be similar when retinopathy, peripheral, and optic neuropathy were separately compared with the complication-naive group (P > .05). However, patients with nephropathy had significantly higher serum levels of AGEs than patients without complications (P = .023). In addition, there was a significant positive correlation between serum AGEs levels and uACR (P = .042) but not other parameters (P > .05). CONCLUSION: This study is the first to evaluate the association between serum AGEs levels and microvascular complications in children and adolescents with T1DM. Our study highlights that serum AGEs levels are significantly correlated with nephropathy but not with retinopathy and neuropathy. Further long-term studies with a larger sample size are required to establish a better relationship between diabetic complications and AGEs. Cite this article as: Kirkgöz T, Acar S, Küme T, et al. Evaluation of serum advanced glycation end product levels and microvascular complications in children and adolescents with type 1 diabetes mellitus. Turk Arch Pediatr. 2024;59(1):31-37.