Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients.

Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX). We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade. Cerebellar ataxia was progressive, slowly leading to disability which was aggravated by axonal polyneuropathy present in almost all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor apraxia (OMA) was present in 32% of the patients while convergent strabismus was present in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more severe in the eldest patients; however it may also be an early sign since it was present in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in all but two patients who presented with head tremor and writer cramp, respectively. Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker to suggest molecular studies of the SETX gene.

Phenotypic variability in autosomal recessive axonal Charcot-Marie-Tooth disease due to the R298C mutation in lamin A/C.

Autosomal recessive forms of axonal Charcot-Marie-Tooth (ARCMT2) disease are frequent in some areas, such as North Africa and the Middle East, since consanguineous marriages are still common there. Recently, a unique homozygous mutation in LMNA, which encodes lamin A/C, a component of the nuclear envelope, was identified in members of three Algerian families with ARCMT2 linked to chromosome 1q21.2-q21.3. In the present study we describe a group of 21 ARCMT2 patients from seven unrelated Algerian families with the same R298C mutation in the lamin A/C gene and marked variability of the clinical phenotype. There is a wide range of age of onset, from 6 to 27 years, with a mean of 14.4 +/- 4.6 years. The course of the disease varies considerably from one patient to another. Twelve patients with a disease duration of 10-15 years had a severe CMT phenotype with distal wasting and weakness of all four limbs and areflexia associated with involvement of the proximal lower limb muscles. In contrast, nine patients had the classical CMT phenotype with mild functional disability without proximal lower limb involvement after a disease duration of 5-18 years. Electrophysiological studies showed a median motor nerve conduction velocity (MNCV) in the normal range in almost all the patients. MNCV and compound muscle action potential (CMAP) values were inversely correlated with the disease duration and the MNCV was strictly related to the CMAP, strongly supporting a pure axonal process without a demyelinating component. Six patients had a nerve biopsy, which revealed severe rarefaction of myelinated fibres in all cases and an increased density of unmyelinated fibres in the majority of cases. In conclusion, the ARCMT2 associated with the R298C mutation differs from other types of ARCMT2. The variability among patients in the age of onset and the course of the disease strongly suggests the action of modifying genes, which remain to be identified.

Identification of seven novel mutations in the GAN gene.

Giant axonal neuropathy (GAN) is a severe early onset neurodegenerative disorder affecting both the peripheral nerves and the central nervous system. The diagnosis is based on the presence of characteristic giant axons on nerve biopsy. In GAN, the integrity of the intermediate filament network is altered. Indeed, abnormal accumulation of the intermediate filaments has been reported in different cell types, including in the swollen axons, which are filled with neurofilaments. We identified the defective protein, gigaxonin, of unknown function, and reported fourteen distinct mutations in twelve families of various origins. Two additional mutations have been recently reported. In the present study, we analysed the GAN gene in 6 families, and identified seven novel mutations: three nonsense and two missense mutations and two deletions. In addition, the molecular result for an already reported family was re-evaluated. In this family, the R269Q "polymorphism" is in fact the pathogenic mutation.

Genetic heterogeneity in giant axonal neuropathy: an Algerian family not linked to chromosome 16q24.1.

Giant axonal neuropathy is a rare severe autosomal recessive childhood disorder affecting both the peripheral nerves and the central nervous system. Peripheral nerves characteristically show giant axonal swellings filled with neurofilaments. The giant axonal neuropathy gene was localised by homozygosity mapping to chromosome 16q24.1 and identified as encoding a novel, ubiquitously expressed cytoskeletal protein named gigaxonin.We describe a consanguineous Algerian family with three affected sibs aged 16, 14 and 12 years who present a mild demyelinating sensory motor neuropathy, hypoacousia and kyphoscoliosis which was moderate in the two elder patients, severe in the third one, with no sign of central nervous system involvement and normal cerebral magnetic resonance imaging. This clinical picture is different from the classical severe form, with kinky hairs and early onset of central nervous system involvement and from the less severe form, with protracted course and late involvement of central nervous system. Nerve biopsy showed a moderate loss of myelinated fibers and several giant axons with thin or absent myelin, filled with neurofilaments. This neuropathological aspect is similar to the previously described families linked to the gigaxonin gene. Genetic study in this family showed absence of linkage to chromosome 16q24.1, indicating for the first time, a genetic heterogeneity in giant axonal neuropathy. We propose to call this form of giant axonal neuropathy giant axonal neuropathy 2, and to use the name of giant axonal neuropathy 1 for the form linked to 16q24.1.

Charcot-Marie-Tooth 2-like presentation of an Algerian family with giant axonal neuropathy.

Giant axonal neuropathy is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. We describe four patients belonging to a consanguineous Algerian family with late onset (6-10 years) slowly progressive autosomal recessive giant axonal neuropathy. The propositus presented with a Charcot-Marie-Tooth 2-like phenotype with foot deformity, distal amyotrophy of lower limbs, areflexia and distal lower limb hypoesthesia. Central nervous system involvement occurred 10 years later with mild cerebellar dysarthria and nystagmus in the propositus and 16 years after onset, a spastic paraplegia in the oldest patient. The two youngest patients (13 and 8 years old) do not present any signs of central nervous involvement. Magnetic resonance imaging showed cerebellar atrophy in the two older. Nerve biopsy showed moderate axonal loss with several giant axons filled with neurofilaments. Genetic study established a linkage to chromosome 16q locus. This clinical presentation differs from the classical form of giant axonal neuropathy.

Congruence of terms between lists of problems and the ICNP--Alpha Version. International Classification for Nursing Practice.

The International Classification for Nursing Practice (ICNP)--Alpha Version, is the first rendition of the International Council of Nurses (ICN) efforts to develop a standardized international nursing language system. This system has three principal components: nursing phenomena; nursing actions; and nursing outcomes. This article describes a study of agreements between terms used by nurses of the intensive care unit at the Hospital of the University of Sao Paulo, to designate patients' nursing problems and the terms proposed by the ICNP--Alpha Version. The records of 59 interned patients, admitted to the intensive therapy unit, were analysed for nursing problems. Of 336 problem categories listed by the nurses, 153 (45.5%) corresponded to the ICNP terms. The 183 categories of problems that did not correspond to the ICNP terms were categorized by the authors as the following: medical diagnoses (37.2%); signs (28.4%); interventions (26.2%); and historical data (8.2%). These results show that there may be no agreement between the concept of nursing phenomena for the ICNP and of nursing problems for the nurses whose records were analysed. Considering that medical diagnoses, intervention and historical data could not be accepted as nursing phenomena for the ICNP, the agreement is potentially higher than 45.5%.

Evaluation of the frequency of anaemia and iron-deficiency anaemia in a group of Algerian menstruating women by a mixed distribution analysis: contribution of folate deficiency and inflammatory processes in the determination of anaemia.

Frequency of anaemia was estimated by two methods for 254 menstruating women living in South-eastern Algeria. One method defines the frequency of anaemia as the percentage of women with haemoglobin concentrations below the cut-off point defined by WHO (12 g/dl). The second method defines the frequency of anaemia as the percentage of women whose haemoglobin values are shifted downwards relative to a Gaussian distribution of haemoglobin of nonanaemic women. The conventional cut-off point probably tends to overestimate the true frequency of anaemia: 7% of women with haemoglobin concentration less than 12 g/dl were not found as anaemic using the cumulative frequency method. The contribution of iron deficiency folate deficiency and inflammatory process was estimated using the cumulative frequency distribution after excluding respectively women with biological evidence of iron deficiency (serum ferritin of 12 micrograms/l or less, transferrin saturation less than 15% and/or MCV less than 80 fl), of folate deficiency (red blood cell folates less than 100 micrograms/l) and of inflammatory process (C. Reactive Protein more than 12 mg/l, orosomucoid more than 1.4 g/l or white cell counts of more than 10,000/mm3). According to this method iron deficiency represented the most important cause of anaemia in the context of our sample: iron deficiency contributed to 77% of anaemia. Folate deficiency and inflammatory processes do not in themselves appear to contribute to anaemia.

[Assessment of the nutritional status of Algerian women in the reproductive age living in an urban, rural and semi-rural area]. / Evaluation de l'état nutritionnel de femmes algériennes en âge de procréer vivant en zones urbaine, rurale et semi-rurale.

We assessed the nutritional status of 302 menstruating women living in three urban, semi-rural and rural areas of eastern Algeria. The anthropometric data and the biochemical measurements (serum levels of total proteins, albumin, transferrin and prealbumin) have shown the absence of protein malnutrition and the evidence of problems of overweight, whatever the criterion used (body mass index or relative weight). There were no differences according to the residence. Anemia (defined by WHO references) was observed in 28% of urban women, 19% of semi-rural women and in 32% of rural women. Iron deficiency (defined by the association of serum ferritin level of 12 micrograms/l or less and transferrin saturation less than 15%) was observed in 29, 27 and 22% of the cases, respectively. Folate deficiency (defined by concentration of red blood cell folates of less than 100 micrograms/l) was observed in 48, 45 and 22% of cases, respectively. Finally, 81% of anemia were associated with biochemical evidence of iron and/or folate deficiency.