Children with a mucopolysaccharidosis or mucolipidosis suffer progressive disability of the hands, particularly in relation to dysfunction of the median nerve. This is an increasing problem because bone-marrow transplantation has dramatically improved survival without apparently changing the musculoskeletal manifestations. We have reviewed 48 children with these syndromes who required carpal tunnel decompression, recording symptoms, signs, radiological, electrophysiological and operative findings, histology and upper-limb function. In these children the carpal tunnel syndrome differs from that seen in adults. Symptoms are rare but signs such as decreased sweating, pulp atrophy, thenar wasting and manual clumsiness are much more common. At operation, the flexor retinaculum was thickened and a mass of white tenosynovium engulfed the flexor tendons. Most patients had some definite nerve constriction with a thickened epineurium.Functional improvement was seen after early decompression, with some benefit from simultaneous tendon release. Regular physiotherapy helped to maintain increased hand movement.We describe our assessment protocol, the physiotherapy and operative regime and the standard functional review which helps to maximise function in the hands and upper limbs of these children.

By presenting the liver with lower collagenase exposure than for the isolation of conventional single hepatocytes (singlets), a preparation is obtained containing -20% of hepatocytes which have not separated from their neighhour at the junctional complex and thus remain as pairs (couplets. doublets) or small multiples; subsequent centrifugal clutriation can enrich the proportion of couplets to -70%.The junctions between the adjacent cells in the couplet are repaired during short-term (4-5h) culture; a sulcd canalicular vacuole is formed from the canalicular components of the two cells. Materials destined for bile can be pumped into this vacuole and accumulatc; the couplets are therefore polarized cells and are acting as rn wino models for the upper pan of the hepatobiliary system. Though possessing no advantage over singlets (indeed they are more difficult to obtain and use) for many metabolic and metabolic control applications couplets have, however, made substantial contributions to our understanding of polarized and hcpatobiliary aspects of hepatocytc function. Singlet hepatocytes have lost this polarity and are thus inappropriate for such studies. In addition to conventional biochemical techniques, work with hepatocyte couplets has made extensive use of visible and fluorescence microscopy, to elucidate: 1) discrimination of hepatounalicular from systemic or ductular effects on bile formation. 2) transcellular movements and canalicular destinations of fluorescent cholephilcs.3) recruitment of transporter molecules to the canalicular membrane and its control. 4) role, control and maturation of tight junctions sealing the bile canaliculus. 5) control and performance of gap junctions between hepatocytes. 6) distribution and control of the cytoskcleton in polarized hepatocytcs. 7) relative contributions of zonal hepatocytc functions in bile formation. 8)m vztro effects and mechanisms of action of cholestatic and hepatotoxic agents.In recent years much has been learned about the functions and hiogenesis of peroxisomes. This increased knowledge has greatly been stimulated by studies on a genetic disease called Zellwegcr syndrome in which peroxisomer are completely lacking due to a defect in pcroxisomc biogcnesis. Most of thc functions of peroxisomes have to do with lipid metabolism and include: 1. Fatty acid beta-oxidation: peroxisomcs catalyse the baa-oxidative chainshortening of a distinct set of substrates including very-long-chain fatty acids, di-and trihydroxycholestanoic acid and 3. pristanic acid, which is the product of the alfa-oxidation of phytanic acid. 2. Etherphospholipid biosynthesis: synthesis of ether-linked phospholipids including plasmalogens is initiated in pcroxisomes since the first 2 enzymatic reactions catalysed by dihydroxyacetone phosphate acyltransferase (DHAPAT) and alkyl DHAP synthase are strictly peroxisomal. 3. Biosynthcsis of isoprenoids including cholesterol: evidence is increasing that pcroxisomcs play an indispensable role in isoprcnoid formation since enzymes such as medonate kinas...

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by “intermediate osteopetrosis”, which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions.

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