Deficiency of respiratory chain complex I is a common cause of Leigh disease.

We reviewed the clinical features and etiologies of Leigh disease in 66 patients from 60 pedigrees. Biochemical or molecular defects were identified in 50% of all pedigrees, and in 74% of the 19 pedigrees with pathologically proved Leigh disease. Isolated deficiency of respiratory chain complex I was found in 7 patients, though the complex was only assayed in 25 patients, making this the second most common biochemical abnormality after complex IV deficiency.

EagI and NotI linking clones from human chromosomes 11 and Xp.

EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability to hybridise with total human DNA and digested with SalI and EcoRI to identify the human insert size and single-copy fragments.

Genetic mapping studies of 40 loci and 23 cosmids in chromosome 11p13-11q13, and exclusion of mu-calpain as the multiple endocrine neoplasia type 1 gene.

Forty loci (16 polymorphic and 24 non-polymorphic) together with 23 cosmids isolated from a chromosome 11-specific library were used to construct a detailed genetic map of 11p13-11q13. The map was constructed by using a panel of 13 somatic cell hybrids that sub-divided this region into 19 intervals, a meiotic mapping panel of 33 multiple endocrine neoplasia type 1 (MEN1) families (134 affected and 269 unaffected members) and a mitotic mapping panel that was used to identify loss of heterozygosity in 38 MEN1-associated tumours. The results defined the most likely order of the 16 loci as being: 11pter-D11S871-(D11S288, D11S149)-11cen-CNTF-PGA-ROM1-D11S480-PYGM- SEA-D11S913-D11S970-D11S97- D11S146-INT2-D11S971-D11S533-11qter.

A common molecular basis for three inherited kidney stone diseases.

Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients and are most commonly associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7).

A case of Pelizaeus-Merzbacher disease showing increased dosage of the proteolipid protein gene.

Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial and spinal root myelin was preserved.

Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults.

Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset.

The familial syndrome of proliferative vasculopathy and hydranencephaly-hydrocephaly: immunocytochemical and ultrastructural evidence for endothelial proliferation.

This is the fourth report of Fowler-type hydranencephaly, or proliferative vasculopathy and hydranencephaly-hydrocephaly (PVHH), and is both the first case in Europe and the first case reported in an Asian family. A 17-week fetus showed severe arthrogryposis, pterygia and muscular hypoplasia. Massive cystic dilatation of the cerebral ventricles with thin disorganized pallium was associated with calcifications and characteristic glomeruloid vasculopathy throughout the CNS.

Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to cellular energy deprivation and their clinico-pathological consequences.

In a search for pathogenic factors that might play roles in the selective vulnerability of brain regions to the lesions of Leigh's disease, archival material from 20 cases of this condition, dying between 1975 and 1992 and aged from 4 days to 11.75 years at death, have been examined. Attention was paid to the topography of the lesions, their nature and timing in the evolution of the disease, the clinico-pathological correlations and the ages of the subjects at onset and at death.

Dysembryoplastic neuroepithelial tumor. Features in 16 patients.

Dysembryoplastic neuroepithelial tumour (DNT) is a newly recognized brain mass lesion with distinctive pathological features and a favourable prognosis. We reviewed the clinical, electroencephalographic, neuroimaging and pathological features of 16 patients with DNT who underwent surgery; only one patient did not have epilepsy. Mean age at seizure onset was 9.

Alexander's disease: clues to diagnosis.

The clinical, radiologic, neurophysiologic, and pathologic findings in 10 children with histologically proven Alexander's disease are described, and the presence of two broad clinical subgroups is confirmed. Macrocephaly, regression, and seizures are found in the infantile form, whereas bulbar signs predominate the so-called juvenile form. None of the clinical or neurophysiologic findings is pathognomonic, and radiologic features suggesting the diagnosis are not present in all cases.

Linkage analysis of 7 polymorphic markers at chromosome 11p11.2-11q13 in 27 multiple endocrine neoplasia type 1 families.

The multiple endocrine neoplasia type 1 (MEN1) locus has been previously localized to 11q13 by combined tumour deletion mapping and linkage studies. Family linkage analysis has defined the locus order as 11 cen-PGA-(PYGM, MEN1)-(D11S97, D11S146)-INT2-11qter, and tumour deletion mapping studies have suggested that the MEN1 locus is proximal to D11S146 but distal to PYGM. In order to establish further the location of MEN1, we have utilized the seven polymorphic DNA probes: D11S288, D11S149, PGA, PYGM, D11S97, D11S146 and INT2, in linkage studies of 339 members (116 affected) from 27 MEN1 families.

Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease.

Fazio-Londe disease is a label sometimes applied to a degenerative disease of the motor neurons characterized by progressive bulbar paralysis in children. It is very rare with only 22 case reports describing 24 children including four sibling pairs. In two reports mothers and sons were affected.

Aluminum-induced neurofilamentous changes in cultured rat dorsal root ganglia explants.

Intrathecal administration of aluminum (AI) salts to susceptible species causes prominent accumulations of neurofilaments (NFs) in neurons of the CNS. Involved nerve cells display abnormal phosphorylation of perikaryal NFs, impaired axonal transport of NFs, and reduced levels of mRNA for NF proteins. Further understanding of the pathogenesis of AI toxicity has been limited by difficulties inherent in the available in vivo systems.

Sinus histiocytosis with massive lymphadenopathy--isolated suprasellar involvement.

An unusual case of an isolated histioproliferative lesion arising from the suprasellar region is described. The presence of lymphophagocytosis suggested that this represented an extranodal intracranial form of sinus histiocytosis with massive lymphadenopathy.

Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim.

Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome.

Two brothers presented with olivopontocerebellar atrophy of neonatal onset. The clinical features (failure to thrive, hypotonia, liver disease, effusions, and visual inattention) were similar to those of the four cases already reported, as were the necropsy findings of olivopontocerebellar atrophy, hepatic steatosis and fibrosis, and microcystic renal changes. The clinical similarities between this and the disialotransferrin developmental deficiency syndrome were noted.

The clinical significance of seizures in critically ill young infants requiring intensive care.

The aetiology, severity of systemic and biochemical abnormalities, seizure duration, EEGs and CT scans have been reviewed in previously normal young infants with an acute critical illness occurring after the first week of life; none of whom had birth asphyxia. Findings were related to outcome in an attempt to evaluate the significance of seizures during the acute phase of severe illness. In three years seizures occurred in 54/251 (22%) young infants requiring ventilatory support.

Intractable seizures from infancy can be associated with dentato-olivary dysplasia.

Five children with severe developmental delay had intractable fits of various types but tonic, often extensor, seizures were prominent from an early stage. Onset was in the neonatal period in 4 cases. EEGs were severely abnormal and showed a "burst-suppression" pattern in the first months of life.

Pelizaeus-Merzbacher disease: classical or connatal?

The clinical features and investigation results of 7 patients with Pelizaeus-Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD.

Propionic acidaemia: a neuropathological study of two patients presenting in infancy.

The clinical and neuropathological findings are described in two children with propionic acidaemia presenting in infancy; they survived for 4 and 16 years respectively. Abnormalities were noted in the basal ganglia of both patients. In one child who clinically had severe athetosis, there was marbling of the corpus striatum.