Delayed Effects of Transcutaneous Organophosphate Poisoning in Four Children.

Contamination or transcutaneous absorption of organophosphates (OP) is rare and there exist only few reports of such manner of poisoning. We report four children from the same family in whom temporal proximity of the disease onset, a detailed interrogation of parents and exclusion of other clinical differentials, led to the diagnosis of transcutaneous intoxication with organophosphates (diazinon). The contamination occurred during the game with a freshly used poison can. Uncommon clinical picture was marked by delayed signs predominantly reflecting certain nicotinic effects (muscle weakness, cramps) along with subtle neuropathic features occurring throughout a few weeks after initial event. Our illustrative cases can further contribute to the better awareness and understanding of variable spectrum of transcutaneous route of OP poisoning.

Ethylmalonic encephalopathy-report of two cases.

Ethylmalonic encephalopathy is a rare metabolic disease presenting in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea and early death. The biochemical characteristics of this autosomal recessive disease are urinary organic acid abnormalities. Recently it has been found to be caused by mutations in the ETHE1 gene, located on Ch19q13. Only about 30 patients have been reported, and we describe two additional cases. The first patient showed a typical clinical picture and biochemical abnormalities, with additional atypical clinical features. Neuroimaging studies showed extensive changes. A new homozygous mutation in exon 3 of the ETHE1 gene was found. The second patient was not investigated genetically; however besides the typical clinical picture and biochemical profile he was found to have cytochrome C oxidase deficiency.

Distinguishing the four genetic causes of Jouberts syndrome-related disorders.

Jouberts syndrome-related disorders are a group of recessively inherited conditions showing cerebellar vermis hypoplasia and the molar tooth sign of the midbrain-hindbrain junction. Recent analyses have suggested at least three loci, JBTS1 (9q34.3), -2 (11p11.2-q12.3), and -3 (6q23), but the phenotypic spectrum associated with each locus has not been delineated. In addition, deletions of the NPHP1 gene, usually responsible for isolated juvenile nephronophthisis, are occasionally encountered among Jouberts syndrome-related disorder patients. Here, we describe four novel families showing evidence of linkage to two of these loci, provide a 3.6Mb refinement of the JBTS2 locus, and perform a detailed comparison of all linked families identified so far, to define the clinical and radiographical hallmarks for each genetic condition. We find that JBTS1 and -3 primarily show features restricted to the central nervous system, with JBTS1 showing largely pure cerebellar and midbrain-hindbrain junction involvement, and JBTS3 displaying cerebellar, midbrain-hindbrain junction, and cerebral cortical features, most notably polymicrogyria. Conversely, JBTS2 is associated with multiorgan involvement of kidney, retina, and liver, in addition to the central nervous system features, and results in extreme phenotypic variability. This provides a useful framework for genetic testing strategies and prediction of which patients are most likely to experience development of systemic complications.

Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria.

Joubert syndrome (JS) is an autosomal recessive disorder marked by agenesis of the cerebellar vermis, ataxia, hypotonia, oculomotor apraxia, neonatal breathing abnormalities, and mental retardation. Despite the fact that this condition was described >30 years ago, the molecular basis has remained poorly understood. Here, we identify two frameshift mutations and one missense mutation in the AHI1 gene in three consanguineous families with JS, some with cortical polymicrogyria. AHI1, encoding the Jouberin protein, is an alternatively spliced signaling molecule that contains seven Trp-Asp (WD) repeats, an SH3 domain, and numerous SH3-binding sites. The gene is expressed strongly in embryonic hindbrain and forebrain, and our data suggest that AHI1 is required for both cerebellar and cortical development in humans. The recently described mutations in NPHP1, encoding a protein containing an SH3 domain, in a subset of patients with JS plus nephronophthisis, suggest a shared pathway.

An early onset form of methylenetetrahydrofolate reductase deficiency: a report of a family from Kuwait.

Methylenetetrahydrofolate reductase deficiency (MTHFR) is a rare autosomal recessive disorder. There have been 68 cases reported to date in the literature [Eur J Pediatr 1998;157 (Suppl 2):S77]. It affects intracellular folate metabolism and results in homocystinuria and hypomethionemia. We report a family in which three children (two boys and one girl) died before the age of 3 months with severe MTHFR deficiency. A fourth affected boy was treated with betaine and he improved clinically and biochemically. We demonstrate the unique dermatological and brain imaging features in a kindred from Kuwait.