Molecular analysis of the spinal muscular atrophy and neuronal apoptosis inhibitory protein genes in Saudi patients with spinal muscular atrophy

Spinal muscular atrophy [SMA] is a common, often fatal, autosomal recessive disease leading to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. The prevalence of SMA cases in the Kingdom of Saudi Arabia [KSA] is much higher than the European and North American population. Deletions or mutations in 2 genes, telomeric form of the survival motor neuron [SMN1] and the neuronal apoptosis inhibitory protein [NAIP], are known to be associated with SMA. The aim of this study is to examine the deletions or interruptions of the SMN1 and NAIP genes in Saudi patients. The study included 121 Saudi SMA patients [type I [60 patients]; type II [26 patients]; and type III [35 patients]]. The deletions or interruptions of the SMN1 and NAIP genes were detected by using polymerase chain reaction. The study was carried out at the King Fahad National Guard Hospital, Riyadh, K.S.A. between 200 and 2002. The homozygous deletions of exons 7 and 8 of the SMN1 gene were found in 94% and 87% of the patients, Exon 5 of the NAIP gene was deleted in 70%, but its deletion was more frequent in SMA type I [93%] as compared to type II [54%] and type III [43%]. Seven patients with SMA diagnosis did not show any of the above homozygous deletions. All 230 control subjects had at least one copy of both SMN1 and NAIP genes, as expected. Our results demonstrate that the deletion rate [94%] of the SMN1 gene in Saudi SMA patients is similar, irrespective of types, compared with patients of other ethnic groups. We also show that the incidence of NAIP deletion is higher in the more severe SMA cases and the dual deletion of the SMN1 and NAIP genes are more common in Saudi SMA type I patients compared with patients of other ethnic groups

Deletion mutatios in the dystrophin gene of Saudi patients with Duchenne and Becker muscular dystrophy

The deletion in the dystrophin gene has been reported for many ethnic groups, but until now the mutations in this gene have not been thoroughly investigated in Saudi patients with Duchenne muscular dystrophy [DMD] and Becker muscular dystrophy [BMD]. We examined the deletion pattern in the dystrophin gene of the Saudi patients applying multiplex-polymerase chain reaction [PCR]. The aim of this study is to describe the outcome of our initial effort to identify mutations in the dystrophin gene in a representative group of Saudi patients with DMD and BMD. Genomic deoxyribose nucleic acid was isolated from 41 patients with DMD and BMD [27 patients confirmed by muscle biopsy and 14 patients with clinical suspicion], 3 patients with limb girdle muscular dystrophy, 12 male relatives of the patients, and 5 healthy Saudi volunteers. A total of 25 exons around the deletion prone regions [hot spots] of the dystrophin gene were amplified. The study was carried out at the King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia between 2000 and 2002. The deletion of one or more exons was found in 21 of 27 DMD and BMD patients confirmed by muscle biopsy. The deletion in the gene was detected in 5 of 14 patients with DMD diagnosis, but not confirmed by dystrophin staining of muscle biopsy. No deletion in the dystrophin gene was detected in control Saudi volunteers, the limb girdle dystrophy patients, and the relatives of patients, as expected. The present study suggests that intragenic dystrophin gene deletions occur with the same frequency in Saudi patients compared with other ethnic groups. The PCR-based deletion analysis provides a reasonable first step in the diagnostic care of Saudi patients who may be afflicted with DMD and BMD

Community survey of neurological disorders in Saudi Arabia: Results of the pilot study in Agrabiah

A pilot study of the Agrabiah area in Al-Khobar was undertaken to field test study methodologies and identify possible limitations and constraints to a planned community survey for neurological disorders in the Eastern Province of Saudi Arabia. The survey used a pre-tested questionnaire administered by trained personnel to all subjects living within 50 blocks randomly selected from the 198 inhabited ones in the area. Subjects with abnormal responses on screening were then evaluated by neurologists using specific guidelines and criteria to establish the diagnosis of neurological disease. One thousand four hundred and eighty-five subjects [98.3% of all eligible subjects] were screened: 227 [15%] had abnormal responses. Of the 202 subsequently evaluated by neurologists, 178 had definite neurological disease. The overall crude prevalence rate [PR] per 1000 population for neurological morbidity was 120.5 [95% confidence limits [CL] 103.5 to 136.5]. Headache syndromes [PR 99.7, CL 83 to 114.7] were common. The other common disorders were seizures [PR 10.2, CL 5.1 to 15.3], peripheral nerve disorders [PR 2.7], and stroke [PR 2.0]. Mental retardation and cerebral palsy were the main pediatric problems with PR[s] of 1.4 and 0.7 respectively. Our results show that a community survey for neurological disorders is feasible in Saudi Arabia and the modified questionnaire was a good screening instrument [sensitivity 94.7%, specificity 96.8%]. However, the findings on the pattern and prevalence of neurological disorders need to be viewed with caution, particularly against the background of the scope of the study and the small number of subjects assessed. Cultural practices, local time and social events, and climatic conditions significantly affected community participation and the coverage achieved by the study. These factors should be considered when planning community surveys in Saudi Arabia and other environments with similar sociocultural settings

Werding Hoffmann's disease [spinal muscular atrophy type I]: a clinical study of 25 Saudi nationals in Al-Khobar

We describe the clinical features of 25 cases of Werdnig Hoffman's disease [spinal muscular atrophy [SMA] type I] seen prospectively over a two-year period at the King Fahd Hospital of the University [KFHU], Al-Khobar. The hospital incidence rate was 1.93 per 1,000 live births [95% confidence limits, 0.80-3.06/1,000]. The estimated prevalence rate for the community was 0.92/10,000 with 0.59-1 .25 per 10,000 children as its 95% confidence limits. The male to female ratio was 2:3. Reduced fetal movements were reported by six mothers; 8 children [32%] had symptoms at birth, and 24 [96%] had symptoms by the time they were six months old. Other features apart from hypotonia, muscle weakness, and absent deep tendon reflexes included head lag with inability to achieve head control at six months [88%], respiratory problems consisting of difficulty with breathing or frequent chest infections [44%], and difficulty with feeding [40%]. Wasting with fasciculations of the tongue was seen in 64%. Death occurred within six months of presentation in 75% of the cases. The parents were consanguineous in 64% of the cases. This high consanguinity rate was probably the major cause for the high population prevalence rate

pattern and type of seizure disorders among a selected group of Saudi Arabian children

In this study 461 children out of 58 702 referred to hospital ranging in age from birth to 12 years were assessed by age, sex and type of seizure disorder. This number amounted to a proportional frequency of 7.8/1000. In those children under 1 year old the most common types of seizures given in rank order were those associated with non-specific infections with hyperthermia, myoclonus, mental retardation with seizures, and infantile seizures In the group 1-5 years convulsions with fever most common, followed by mental retardation with seizures; tonic-clonic seizures were significantly more common than in the youngest group. In the oldest group [6-12 years] tonic-clonic seizures were most common. Single seizures were only apparent among those with convulsions associated with fever. Birth trauma was most often associated with mental retardation with seizures and myoclonic seizures. Although there was a changing pattern with age, mental retardation with seizures was relatively constant in all age groups averaging 22% of all cases. The results are comparable with the rate and type reported in studies from the highly industrialized nations