Novel V97G ASAH1 mutation found in Farber disease patients: unique appearance of the disease with an intermediate severity, and marked early involvement of central and peripheral nervous system.

Farber disease is a rare inherited lysosomal storage disorder caused by ceramidase deficiency that leads to accumulation of ceramide in various tissues. Mutations within ASAH1 encoding for acid ceramidase are responsible for the disease. Here we report two siblings with Farber disease who carry a novel V97G with the parents and a sister being asymptomatic carriers. The mutation site was found to be highly conserved among different species using ClustalW2 alignment. Functional prediction tools indicated the mutation to be pathogenic. Electron microscopy based ultrastructural studies using skin biopsy showed inclusion of enlarged lysosomes and presence of the zebra bodies. The T1 weighted magnetic resonance images of the brain indicated diffuse loss of the deep white matter volume predominantly along the occipital horns of the lateral ventricle with subsequent facet dilatation of the supratentorial and infratentorial ventricular system. This is the first report of a detailed clinical and molecular analysis of cases with Farber disease from Saudi Arabia.

Profound biotinidase deficiency in a child with predominantly spinal cord disease.

Biotinidase deficiency is an autosomal recessively inherited disorder that manifests during childhood with various cutaneous and neurological symptoms particularly seizures, hypotonia, and developmental delay. Spinal cord disease has been reported rarely. We describe a 3-year-old boy with profound biotinidase deficiency who presented with progressive spastic paraparesis and ascending weakness in the absence of the usual characteristic neurological manifestations. Supplementation with biotin resulted in resolution of paraparesis with persistent mild spasticity in the lower limbs. DNA mutation analysis revealed that he was homozygous for a novel missense mutation (C>T1339;H447Y) in the BTD gene. This case indicates that biotinidase deficiency should be included in the differential diagnosis of subacute myelopathy and emphasizes the importance of a prompt diagnosis to prevent irreversible neurological damage.

Cephalosporin-induced nonconvulsive status epilepticus in a uremic child.

The temporal relationship between convulsive seizures and the administration of beta-lactams has long been recognized. A specific form of seizures, nonconvulsive status epilepticus, is less common and is often manifested by alterations in mental status without associated seizures. It is most commonly encountered in uremic patients and poses a diagnostic challenge because of its nonspecific clinical manifestations. In this report, we describe a child with chronic renal failure who developed nonconvulsive status epilepticus on two separate occasions after administration of a third-generation cephalosporin. Awareness of this potentially treatable condition is crucial to ensure appropriate and prompt medical therapy. To our knowledge, this is the first report of cephalosporin-induced nonconvulsive status epilepticus in a child with chronic renal failure.