Encephalopathy, Progressive, With Or Without Lipodystrophy

A number sign (#) is used with this entry because progressive encephalopathy with or without lipodystrophy (PELD) is caused by homozygous or compound heterozygous mutation in the BSCL2 gene (606158) on chromosome 11q13.

Biallelic mutation in the BSCL2 gene can also cause congenital generalized lipodystrophy type 2 (CGL2; 269700), which is not associated with severe neurologic deterioration.

Description

Progressive encephalopathy with or without lipodystrophy is a severe neurodegenerative disorder characterized by developmental regression of motor and cognitive skills in the first years of life, often leading to death in the first decade. Patients may show a mild or typical lipodystrophic appearance (summary by Guillen-Navarro et al., 2013).

Clinical Features

Guillen-Navarro et al. (2013) reported 6 children from 4 families from Murcia in southeastern Spain with a severe progressive encephalopathy. The patients developed symptoms between ages 2 and 3 years, and 5 of them died between ages 6 and 8 years. Features included psychomotor regression, loss of speech, poor motor coordination with increased muscle tone, spasticity, ataxia, tremor, myoclonus, dystonia, and seizures. Most of the patients died from respiratory failure or respiratory infection. Brain MRI of 1 patient showed progressive cerebral atrophy. Five of the patients showed a mild lipodystrophic phenotype, with a lipoatrophic appearance, but only some had hypertriglyceridemia and hepatomegaly. The lipodystrophic appearance regressed in at least 1 patient. At age 3.5 years, another patient had mild psychomotor delay, a lipoatrophic appearance, and brain hypometabolism. Postmortem examination of 1 patient showed severe lack of subcutaneous and visceral adipose tissue. Preadipocyte cytoplasm contained markedly dilated rough endoplasmic reticulum (ER) filled with granular material as well as protein evidence of increased ER stress. Neuropathologic examination showed cerebral and cerebellar atrophy, atrophy of the caudate, neuronal loss, astrogliosis, and phosphorylated neurofilaments containing axonal spheroids in remaining neurons.

Inheritance

The transmission pattern of PELD in the families reported by Guillen-Navarro et al. (2013) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 6 children from 4 unrelated families from Murcia in southeastern Spain with autosomal recessive progressive encephalopathy with or without lipodystrophy, Guillen-Navarro et al. (2013) identified homozygous or compound heterozygous truncating mutations in the BSCL2 gene (606158.0017-606158.0019). All patients carried the same mutation (c.985C-T; 606158.0017) on at least 1 allele, consistent with a founder effect.