X‐linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course

Abstract

An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before.

Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders

“…6 Autopsy of one individual who died at five and a half years of age revealed complete absence of myelinated axons in the posterior columns of the spinal cord, but no abnormalities were seen in the brain stem or in the gray and white matter of the cerebral and cerebellar hemispheres. 2 Our patients presented with central nervous abnormalities including thin corpus callosum with the lack of isthmus and atrophied or hypoplastic optic chiasm. The white matter showed delayed maturation and thinning, signs that had not been previously recognized in this spectrum of disorders.…”

“…These patients presented with intellectual disability, early-onset hypotonia, ataxia, delayed motor development, hearing impairment, optic atrophy and susceptibility to infections. 2 De Brouwer and co-workers 6 reported the original Dutch family described by Arts et al, 2 in addition to two additional Australian male patients. They all had undetectable hypoxanthine in urine and reduced uric acid levels in the serum.…”

Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood

“…The family with an X-linked mental retardation syndrome (Arts et al 1993) was analyzed for cosegregation with a set of highly polymorphic markers from loci distributed along the entire X chromosome. The results of two-point linkage analysis are summarized in Table 1.…”

“…W e perform ed linkage analysis in a family with a syndrom ic developm ental delay, previously described by Arts et al (1993;M IM no. 301835, Fig.…”

Multi-system signs and symptoms in X-linked ataxia carriers

“…Recently a disorder with an early onset has been described that af fected at least the posterior columns, peripheral motor and sensory neurons, the cranial nerves and/or nuclei; this resulted in ataxia, muscle weakness, deafness and visual impairment (Arts et al, 1993). Recurring infections were the cause of death in all the cases before the age of 5 years, except for one.…”