Hyperferritinemia-cataract syndrome is a disorder characterized by an excess of an iron storage protein called ferritin in the blood (hyperferritinemia) and tissues of the body. A buildup of this protein begins early in life, leading to clouding of the lenses of the eyes (cataracts). In affected individuals, cataracts usually develop in infancy, rather than after age 60 as typically occurs in the general population. Cataracts that are not removed surgically cause progressive dimming and blurriness of vision because the clouded lenses reduce and distort incoming light.\n\nAlthough the hyperferritinemia in this disorder does not usually cause any health problems other than cataracts, the elevated ferritin levels in the blood can be mistaken for a sign of certain liver disorders. These conditions result in excess iron in the body and may be treated by blood-drawing. However, individuals with hyperferritinemia-cataract syndrome do not have an excess of iron, and with repeated blood draws will develop reduced iron levels leading to a low number of red blood cells (anemia). Therefore, correct diagnosis of hyperferritinemia-cataract syndrome is important to avoid unnecessary treatments or invasive test procedures such as liver biopsies.

Neurodegeneration with brain iron accumulation-9 (NBIA9) is characterized by global developmental delay apparent from infancy and progressive neurodegeneration of motor and cognitive skills. Affected individuals have delayed walking or inability to walk, spasticity with hyperreflexia, ataxia, dystonia, and poor or absent language. Additional more variable features include dysphagia, failure to thrive, poor growth, microcephaly, hypotonia, impaired vision, and seizures. Brain imaging shows progressive cerebral and cerebellar atrophy, iron accumulation in the basal ganglia, thin corpus callosum, and pontocerebellar hypoplasia. The disorder can be classified as a neuroferritinopathy (see NBIA3, 606159) (Shieh et al., 2023). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200).