A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom.

Charcot-Marie-Tooth disease type 4D (CMT4D), also known as hereditary motor and sensory neuropathy Lom type (HMSNL), is an autosomal recessive, early onset, severe demyelinating neuropathy with hearing loss, caused by N-Myc downstream-regulated gene 1 (NDRG1) mutations. CMT4D is rare with only three known mutations, one of which (p.Arg148Ter) is found in patients of Romani ancestry and accounts for the vast majority of cases. We report a 38-year-old Italian female with motor development delay, progressive neuropathy, and sensorineural deafness. Magnetic resonance imaging showed slight atrophy of cerebellum, medulla oblongata, and upper cervical spinal cord. She had a novel homozygous NDRG1 frameshift mutation (c.739delC; p.His247ThrfsTer74). The identification of this NDRG1 mutation confirms that CMT4D is not a private Romani disease and should be considered in the differential diagnosis of recessive demyelinating CMT.

Expanded HSAN4 phenotype associated with two novel mutations in NTRK1.

Hereditary sensory and autonomic neuropathy type IV (HSAN4) is a severe autosomal recessive disorder characterized by childhood onset of sensory and autonomic dysfunction leading to hyperthermia, recurrent infections and physical impairment due to complications of osteoarthritis. Cognitive impairment and aggressive behaviour is common. HSAN4 is caused by mutations in the NTRK1 gene coding for the tyrosine kinase receptor A. We present detailed description of a rare, mild HSAN4 phenotype associated with two novel NTRK1 mutations. This Swedish patient presents with an adult onset of painful Charcot arthropathy, prolonged wound healing, discrete polyneuropathy, hypohidrosis without further autonomic dysfunction and no cognitive affection.

Skeletal abnormalities in Refsum's disease (heredopathia atactica polyneuritiformis).

Refsum's disease is a rare inborn error of phytanic acid metabolism in which skeletal abnormalities are part of the clinical syndrome. The reported incidence of bone changes in patients with Refsum's disease varies widely and reflects the small series published to date. An analysis of the skeletal abnormalities of the largest series of patients in the world is presented.

Skeletal changes in Refsum's disease.

Refsum's disease is a rare inherited disease of lipid metabolism. The cardinal diagnostic features include polyneuritis, cerebellar ataxia, an atypical pigmentosa and a high CSF protein. The disorders is accompanied by the accumulation in the tissues, especially the liver and kidneys, of the lipid 'phytanic acid'. The disease is due to the absence of the enzyme phytanic acid alpha-hydroxylase which catalyses the conversion of phytanic acid to alpha-hydroxy phytanic acid the initial step in its further metabolism. In his original monograph Refsum (1945) documented a number of skeletal abnormalities and the full spectrum of changes that occur has become clear though the accumulating subsequent reports. This paper documents the osseous changes in three members with the disease in a single family. These include epiphyseal dysplasia, especially pronounced in the knees, and shortening and deformity of many of the tubular bones in the hands and feet.