الفهرس 
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Abstract
Huntington disease (HD) is a disabling fatal neurodegenerative disorder with motor, psychiatric and cognitive manifestations which may mimic in its early stages other neurological and psychiatric diseases. HD runs a progressive course that ends in death after duration of 10 to 15 years .It is well established that HD, though more common in middle age but it can affect any age even children with characteristic clinical features for each age group of affected patients.
The pathogenesis of HD involves an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The subsequent change in the Huntingtin protein causes death of the neuronal cells in the basal ganglia. Diagnosis is based on clinical suspicion and is confirmed by DNA determination.
The present study aimed to confirm the diagnosis of Huntington disease by molecular testing in clinically probable or doubtful cases, especially the sporadic cases that do not exhibit a family history for HD which will allow proper management and genetic counselling of the affected patients and their families.The study also aimed at evaluating the clinical presentations of molecularly confirmed HD patients and to correlate the clinical manifestations of the disease with the genotype. The present study included thirty three patients with signs and symptoms suggestive of Huntington disease from the cases referred to the Human Genetics Department, Medical Research Institute, Alexandria University, and from the out-patient clinic of El Hadara University hospital (the psychiatry and neurology department).
The Huntington allele positive patients were subdivided into three groups according to their age of onset:
(1) The juvenile group: with age less than 20 years, this group included three males (3/ 16; 18.5%) they were brothers. The mean repeat number in this group for the higher allele was 66 while for the lower allele it was 17. All the cases in this group had a positive family history (transmitting father).
(2) The adult group: with age ranged from 20 years to below 60 years. Ten patients were included in this group (10 /16; 62.5 %). Positive family history for Huntington disease was found in eight cases (8/10;80%) .The mean repeat number in this group for the higher allele was 50 while for the lower allele it was 23.
(3) The late onset group with age above 60 years. This group included three sporadic cases (one male and two females).The mean repeat number in this group for the higher allele was 51 while for the lower allele it was 22.
Paternal transmission was found in five cases (5 /16; 31.25%) in the three juvenile cases and in two cases (2/ 10; 20%) from the adult group. Maternal transmission was noted in five cases (5/16; 31.25%) all from the adult group.
The onset symptoms in the Huntington disease patients were:
d- Psychiatric manifestations: were the onset symptoms in 25% of cases. It is more pronounced in the juvenile group.
e- Motor manifestations: were observed in 62.5% of cases. They were more prominent in group II and group III while they were absent in group I.
f- Cognitive decline and dementia: were found in one patient from the juvenile group while dementia was found in one patient from the adult group.
The Clinical manifestations in Huntington disease patients were:
a- Cognitive manifestations: were observed in 75% of cases, in all the cases of the juvenile group and in 80% from the adult group while in the late group it was found in one patient.
Dementia was observed in 18.75% of cases. It was more pronounced in the juvenile group (66.66%).Only one case from the adult group suffered from dementia while it was absent in the late onset group.
b- Psychiatric manifestations: were more predominant in the juvenile group (100%) followed by the adult group (70%) while they were absent in the late group.
c- Motor manifestations were noted in all patients (100 %).
Assessment of the cognitive functions in HD patients by the Mini mental state examination (MMSE): The severe score was higher in the juvenile group (2/3; 66.66%).The mild MMSE score was more prevalent in the adult group (5/10; 50%) compared to the juvenile and late groups (0/3 and 1/3) respectively.
The Dementia Rating Scale (CDR): Two cases from the juvenile group (2/3; 66.66%) had a severe CDR score while only one case from the adult group had a severe score.
MRI brain of HD patients showed: severe volume loss in the basal ganglia in 25% of all patients, with a higher predominance in the juvenile group (66.66%). Mild cerebral atrophy was more pronounced in the late onset group (66.66%).
Molecular diagnosis of the HD patients done by PCR revealed the following:
The Mean of higher repeat in the affected HD patients was 52.8. In the juvenile group the mean for higher repeat was 66 which is higher than the adult and late groups (49.5 and 50.6 respectively)
The repeats higher than 60 were mainly observed in the juvenile group (100%), while repeats from 50 – 60 were found in two cases (20%) and two cases (66.66%) from the adult and late groups respectively. The repeats from 40-49 were noted in five cases from the adult group (31%). Only one case from the adult group had a 37 repeat.
The molecular testing of the control group:
The highest repeat frequency (32%) was for the repeat 17 while repeat 27 showed the lowest repeat frequency (14%).
The cases with negative HD allele were 17; the male to female ratio was 8: 9 patients. The cases with a positive family history for neurological or psychiatric disorders represented (29.4%) .The clinical manifestation among the cases with negative HD allele were motor in (70.6%) while psychiatric manifestations and cognitive decline were observed in (17.6 %) and (11.8%) respectively.
Conclusion: In the present study, the sixteen positive HD cases were divided into juvenile, adult and late groups according to their age of onset. There was a male predominance notably in the juvenile group. Most of the cases had a positive family history for Huntington disease. Maternal transmission was equal to the paternal transmission in all the patients. The onset symptoms of the affected patients were mainly motor in the majority of patients with a higher frequency in the adult onset group. There was a higher predominance for chorea as an onset symptom. The psychiatric onset symptoms were specially noted in the juvenile group.
The motor symptoms were the highest among all clinical manifestations being observed in all affected cases. Chorea was the most frequent motor manifestation being found in the majority of the adult group, furthermore, rigidity was found in all the cases of the juvenile group. Cognitive decline and psychiatric manifestations showed a higher predominance in the juvenile and adult groups.
Molecular testing for the patients in the current study revealed that the repeats above 60 CAG had the highest frequency being more predominant in the juvenile group followed by repeats from the range 40-49 which were more pronounced in the adult group. In the normal control group the highest frequency was for repeat 17.
Huntington disease is one of the underestimated disorders, the prevalence of the disease is suspected to be higher than the reported figures due to missed diagnosis. The similarity of the clinical picture of Huntington disease to other psychiatric and neurologic disorders makes the molecular analysis a valuable tool in the diagnosis specially since the mutation for Huntington disease is specific and the genetic test is highly sensitive.