Background: Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder characterized by a constellation of symptoms, including alopecia, hypogonadism, diabetes, mental retardation, and extrapyramidal syndrome. Here, we present a case study of a girl with WSS, focusing on clinical features, genetic analysis, and treatment. Case Description: The patient is a 16-year-old female who presented with primary amenorrhea and underdeveloped secondary sexual characteristics. She has first-degree consanguineous parents. Clinical evaluations, laboratory tests, whole-exome sequencing, and karyotyping were performed to diagnose WSS. The patient exhibited notable frontotemporal alopecia, hypogonadism, and intellectual decline. Genetic analysis revealed a homozygous mutation (c.1001 + 1G > A) in the DCAF17 gene, a known causative gene of WSS. In addition to hormone therapy to induce puberty, the patient was referred to neurology for further evaluation. Conclusions: This case highlights the importance of considering WSS in patients with alopecia, hypogonadism, and consanguineous backgrounds. Genetic testing plays a crucial role in diagnosis, while hormone therapy may alleviate some symptoms. WSS is a complex syndrome with varied clinical manifestations, necessitating multidisciplinary treatment. Early recognition and effective management are essential for improving the quality of life of affected individuals.

Neurodegeneration with brain iron accumulation (NBIA) refers to a group of rare genetic disorders characterized by abnormal iron deposition in the basal ganglia and brainstem due to impaired iron homeostasis. Disease severity and manifestations vary according to the underlying genetic mutation and age of presentation; however, most subtypes share progressive neurological features such as dystonia, Parkinsonism, spasticity, cognitive decline, and intellectual disability. In this review, we first outline the physiological role of iron in the central nervous system, emphasizing its importance for neurotransmitter synthesis, myelination, and mitochondrial metabolism, and discuss how disruption of homeostatic mechanisms may lead to ferroptosis and neuronal injury. We then explore the role of neuroimaging in the diagnosis of NBIA, with a focus on MRI as the modality of choice. Finally, we provide an overview of the clinical and imaging features of the major NBIA subtypes, highlighting both shared characteristics and distinctive patterns. Covered NBIA include primary disorders of iron metabolism, such as neuroferritinopathy and aceruloplasminemia, and secondary disorders with disrupted iron regulation, including Pantothenate Kinase-Associated Neurodegeneration, Phospholipase A2 Group VI-Associated Neurodegeneration, Mitochondrial Membrane Protein-Associated Neurodegeneration, Beta-Propeller Protein-Associated Neurodegeneration, Fatty Acid Hydroxylase-Associated Neurodegeneration, Coenzyme A Synthetase Protein-Associated Neurodegeneration, Woodhouse-Sakati syndrome, and Kufor-Rakeb Disease. By integrating genetics, pathophysiology, and imaging, this review aims to improve recognition of NBIA and support comprehensive clinical management.

Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this chapter, we discuss ten NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are pantothenate kinase 2-associated neurodegeneration (PKAN), neuroferritinopathy, aceruloplasminemia, Kufor-Rakeb disease (KRD), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Woodhouse-Sakati syndrome (WSS), beta-propeller protein-associated neurodegeneration (BPAN), mitochondrial membrane protein-associated neurodegeneration (MPAN), and coenzyme A synthase protein-associated neurodegeneration (CoPAN). An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine disorder characterized by a variety of endocrine and neurological manifestations, including extrapyramidal symptoms and intellectual disability. This report presents the genetic characterization of five Iranian patients with WSS, including the first Iranian patient to undergo deep brain stimulation (DBS). We highlight five Iranian patients with mutations in the DCAF17 gene presenting with variable features of WSS, with symptom onset in early adolescence. Whole exome sequencing identified four homozygous variants (c.436delC, c.982-2A>G, c.580C>T, and c.838+1G>A) within the DCAF17 gene in the probands. Patients had variable responses to common therapies, and one patient achieved significant improvement following DBS. We expand the clinical and genetic heterogeneity among Iranian patients and suggest the c.436delC variant as a founder mutation in the region. We highlight the importance of considering WSS in patients with both neurological and endocrine symptoms and suggest DBS as a potential treatment option. The purpose of this overview is to: 1.. Briefly describe the clinical characteristics of neurodegeneration with brain iron accumulation (NBIA); 2.. Review the genetic causes of NBIA; 3.. Review the differential diagnosis of NBIA with a focus on genetic conditions; 4.. Provide an evaluation strategy to identify the genetic cause of NBIA in a proband (when possible); 5.. Review high-level management of NBIA; 6.. Inform genetic counseling of family members of an individual with NBIA.