Atherosclerosis, Premature, With Deafness, Nephropathy, Diabetes Mellitus, Photomyoclonus, And Degenerative Neurologic Disease

Feigenbaum et al. (1990, 1994) described 2 brothers with this combination. The proband presented at age 22 years with deteriorating cognitive function, sensorineural deafness, and proteinuria. At the age of 27 years, diabetes mellitus and renal artery stenosis were diagnosed. Renal biopsy showed glomerular sclerosis and mesangiolysis. Progressive neurologic deterioration with cerebellar symptoms and photomyoclonic seizures ensued. Death occurred at age 31 years. Autopsy showed severe atherosclerosis of renal, coronary, and cerebral arteries and the aorta. Diffuse neuronal loss and gliosis of the cerebral deep gray matter, cerebellum and dentate nuclei were found, as well as scattered infarcts throughout the brain. A brother died at age 26 years with similar clinical and pathologic findings. Studies of 2 sisters and the parents were normal. In vitro studies of cultured skin fibroblasts documented partial deficiencies of complexes 3 and 4 of the mitochondrial respiratory chain. This deficiency was expressed in skin fibroblasts, kidney, and liver, but not in muscle. The findings were thought to be compatible with mitochondrial, autosomal recessive, or X-linked recessive inheritance. Many of the features were similar to those in Herrmann syndrome (172500), but that condition appeared to be autosomal dominant and there were different pathologic findings, namely, PAS-positive deposits in the dentate and olivary nuclei as well as the renal collecting tubules.