Optic nerve enlargement in Krabbe disease: a pathophysiologic and clinical perspective.

Krabbe disease is an infantile-onset progressive leukodystrophy. The classic presentation includes excessive irritability, muscle hypertonicity, developmental delay, failure to thrive, peripheral neuropathy, seizures, and optic nerve atrophy. The authors report a rare case of optic nerve enlargement early in infantile Krabbe disease. Their case demonstrates proximal prechiasmatic enlargement of the nerves. They discuss the pathophysiological and clinical correlation of optic nerve enlargement in Krabbe disease and in other disorders. Although Krabbe disease does not feature in initial differential of optic nerve enlargement in children, its inclusion and early identification facilitate a timely diagnosis of this rapidly progressive fatal disease.

Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency.

Human FOXP2 deficiency has been identified as a cause of hereditary developmental verbal dyspraxia. Another member of the same gene family, FOXP1, has expression patterns that overlap with FOXP2 in some areas of the brain, and FOXP1 and FOXP2 have the ability to form heterodimers. These findings suggest the possibility that FOXP1 may also contribute to proper speech development. However, no such role of FOXP1 has been established to date. Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges. The nature of the speech deficit is different from the primary oromotor verbal dyspraxia found in patients with FOXP2 deficiency. The patient's developmental deficits may support a role for FOXP1 in the development of verbal and motor skills.

X-linked creatine transporter deficiency presenting as a mitochondrial disorder.

X-linked creatine transporter defect is caused by mutations in SLC6A8 at Xq28, which encodes the sodium-dependent creatine transporter. Reduction in creatine uptake results in elevated urine creatine and CSF creatine deficiency, which can be detected on magnetic resonance spectroscopy. We report a patient who was initially suspected of having a mitochondrial disorder but was later found to have a creatine transporter defect. The abnormal laboratory study results seen in this patient suggesting a mitochondrial cytopathy could be due to excess mitochondrial stress as well as the mitochondrial inclusion bodies. This report looks at the mitochondrial presentation of the creatine transporter deficiency.

Metabolic disorders causing childhood ataxia.

Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.