Non-syndromic isolated congenital deafness was found in 2 other family members, although they were otherwise unaffected.The third case report was made by Valero et al in 2008, they described a 60-year old man and his 81-year-old mother from France. The both of them had noninsulin-dependent diabetes mellitus and childhood-onset hearing loss. Out of the 2 patients, the mother was the most affected, her phenotype consisted of additional features her son didnt suffer from including severe vision impairment, bilateral optic nerve atrophy. Even though both of them had hearing impairments, the son was the only one of the pair who wore a hearing aid, the mother didnt do so, and as a result she had very obvious difficulties comprehending speech.The fourth case report was made by Hogewind et al, their patients were 3 affected members of a 2-generation Dutch family (2 brothers and their mother). The three of them suffered from hearing loss ranging from moderate to severe and optic neuropathy but they didnt have any other symptoms, including the ones usually associated with both Wolfram syndrome and Wolfram-like syndrome (such as diabetes mellitus/insipidus or depression), but they did have red-green color deficiency. The elder sibling and the mother were found to have severe hearing loss which heavily diminished their ability at recognizing speech, while the younger brother was relatively okay at doing so. All three individuals were found to have ocular scotoma (also known as blind spot) and neuroretinal rim loss.
Use of benzodiazepines in the elderly is only recommended for 2 weeks and it is also recommended that half of the usual daily dose is prescribed. Pharmacology
Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half life of 20 – 179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam. Clorazepate exerts its pharmacological properties via increasing the opening frequency of the chloride ion channel of GABAA receptors. This effect of benzodiazepines requires the presence of the neurotransmitter GABA and results in enhanced inhibitory effects of the neurotransmitter GABA acting on GABAA receptors. Clorazepate, like other benzodiazepines, is widely distributed and is highly bound to plasma proteins; clorazepate also crosses readily over the placenta and into breast milk. Peak plasma levels of the active metabolite desmethyl-diazepam are seen between 30 minutes and 2 hours after oral administration of clorazepate. Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam. Chemistry
Clorazepate is used in the form of a dipotassium salt. It is unusual among benzodiazepines in that it is freely soluble in water. Clorazepate can be synthesized starting from 2-amino-5-chlorobenzonitrile, which upon reaction with phenylmagnesium bromide is transformed into 2-amino-5-chlorbenzophenone imine. Reacting this with aminomalonic ester gives a heterocyclization product, 7-chloro-1,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one.