GFAP mutations, age at onset, and clinical subtypes in Alexander disease.

OBJECTIVE: To characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein (GFAP) mutations. METHODS: We present 30 new cases of AxD and reviewed 185 previously reported cases. We conducted Wilcoxon rank sum tests to identify variables scaling with AAO, survival analysis to identify predictors of mortality, and χ(2) tests to assess the effects of common GFAP mutations. Finally, we performed latent class analysis (LCA) to statistically define AxD subtypes. RESULTS: LCA identified 2 classes of AxD. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features. Survival analysis predicted a nearly 2-fold increase in mortality among patients with type I AxD relative to those with type II. R79 and R239 GFAP mutations were most common (16.6% and 20.3% of all cases, respectively). These common mutations predicted distinct clinical outcomes, with R239 predicting the most aggressive course. CONCLUSIONS: AAO and the GFAP mutation site are important clinical predictors in AxD, with clear correlations to defined patterns of phenotypic expression. We propose revised AxD subtypes, type I and type II, based on analysis of statistically defined patient groups.

Rasmussen encephalitis associated with Parry-Romberg syndrome.

Parry-Romberg syndrome is a rare disorder associated with unilateral facial atrophy involving skin, subcutaneous tissue, skeletal muscle, and bone. Occasionally, there is CNS involvement with epilepsy being the most common CNS manifestation. The authors report a child with Parry-Romberg syndrome with a course strongly suggestive of Rasmussen encephalitis. The boy underwent hemispherectomy, and pathology showed the typical findings of Rasmussen encephalitis, suggesting that these two conditions may share common etiologic factors.

Leigh syndrome in an infant resulting from mitochondrial DNA depletion.

Leigh syndrome is an encephalomyelopathy that results from a heterogeneous group of mitochondrial disorders characterized by symmetric brainstem spongioform lesions. An infant born with hypotonia and lactic acidosis was found to have symmetric brainstem lesions on T(2)-weighted magnetic resonance imaging consistent with Leigh syndrome. Muscle biopsy failed to reveal ragged-red fibers or cells devoid of cytochrome C oxidase or succinate dehyrogenase. Southern blot analysis of mitochondrial DNA isolated from the patient's quadriceps muscle indicated severe mitochondrial DNA depletion, which was suggested as the cause for the Leigh syndrome seen in this patient. Consideration of mitochondrial DNA depletion as an etiology when evaluating the patient with Leigh syndrome is encouraged.

The mechanism of iron release from transferrin. Slow-proton-transfer-induced loss of nitrilotriacetatoiron(III) complex in acidic media.

The role of protonation of amino acid ligands involved in iron release from human serum transferrin, previously saturated with nitrilotriacetatoiron(III) complex, has been elucidated in acidic media. Iron loss occurs first from the N-terminal site at pH < 6 and is followed at pH < 4 by iron release from the C-terminal iron-binding site. Nitrilotriacetatoiron(III) release from the N-terminal site is controlled by the slow protonation of the mixed protein/nitrilotriacetatoiron(III) complex; the second-order rate constant was k3a = 9.95 +/- 0.35 x 10(4) M-1.s-1. Protonation of an amino acid ligand in the C-terminal site leads to a new protein-site-C-loaded mixed complex with dissociation constant K4 = 0.300 +/- 0.025 mM. Nitrilotriacetatoiron(III) release is the result of mixed complex dissociation and the slow rate-limiting protonation of the iron-free protein with a proton dissociation constant K5a = 0.100 +/- 0.010 mM and a second-order rate constant k5a = 4.20 +/- 0.40 x 10(3) M-1.s-1. The mechanism of iron uptake and release seems to imply that slow proton transfers can induce complex formation between iron and the amino acid ligands of each of the protein iron-binding sites. These slow proton transfers may be controlled by the change of conformation of the binding sites upon iron loss.

Vaginal "fisting" as a cause of death.

We describe the death of a young girl that resulted from the insertion of a clenched hand and forearm into her vagina during heterosexual activity. (The male homosexual practice of rectal fist insertion has been described previously.) We believe this death to be the first reported case of a "fisting" death due to vaginal fist insertion during heterosexual activity. This death is reported to alert forensic pathologists, medicolegal death investigators, and coroners aware of the role of aberrant sexual activity and its potential to cause death.

A burning issue. The Japanese "fire basin".

This article presents two deaths due to acute carbon monoxide poisoning that occurred when charcoal-burning hibachis were used as heating sources in enclosed camping facilities. In both deaths, the levels of blood carbon monoxide saturation were at or slightly below the expected lethal level. Coronary arteriosclerosis may have contributed to one death, while oxygen depletion may have been a contributing factor in the other. These cases illustrate the danger of using such heating sources in enclosed spaces, due to their carbon monoxide-generating capability. We suggest that suitable warnings be placed on the hibachis themselves.

An unusual case of child abuse homicide/suicide.

This case report examines a child abuse homicide in which the perpetrator committed suicide a few hours after the infant's death. At the time of the perpetrator's suicide he was not under investigation, nor was he a suspect in the death of the child. Although the literature does not contain reports of similar cases, we are sure they exist. This report raises the question of the degree of social stigma attached to the accusation of child abuse. It also serves as a warning to those who must deal with the potentially suicidal child abuser.

Preformed hydroxylapatite blocks for palatal grafting in orthognathic surgery.

Hydroxylapatite has been used as a bone substitute for ridge augmentation, ridge maintenance and periodontal defects for many years. This is a preliminary report of the use of hydroxylapatite blocks as a grafting material in midpalatal splits in orthognathic surgery. With the advent of hydroxylapatite blocks, the need for autogenous bone grafting will, in most cases, be obviated.

Use of preformed hydroxylapatite blocks for grafting in genioplasty procedures.

Dense hydroxylapatite is a synthetic, biocompatible, immunologically inert material that can establish a chemical union with bone when placed in intimate contact in histologic studies. The following is a preliminary report of the use of preformed dense, non-resorbable hydroxylapatite blocks as a grafting material for use in advancement and vertical lengthening of the bony chin associated with orthognathic surgical procedures. In rare instances where an autogenous bone graft would be required for vertical lengthening without any advancement of bony pogonion, the need is obviated by utilization of the hydroxylapatite solid block.