X-linked recessive chondrodysplasia punctata is a type of chondrodysplasia punctata that can involve the skin, hair, and cause short stature with skeletal abnormalities, cataracts, and deafness. : 500 This condition is also known as arylsulfatase E deficiency, CDPX1, and X-linked recessive chondrodysplasia punctata 1. The syndrome rarely affects females, but they can be carriers of the recessive allele. Although the exact number of people diagnosed with CDPX1 is unknown, it was estimated that 1 in 500,000 have CDPX1 in varying severity. This condition is not linked to a specific ethnicity. The mutation that leads to a deficiency in arylsulfatase E. (ARSE) occurs in the coding region of the gene. Absence of stippling, deposits of calcium, of bones and cartilage, shown on x-ray, does not rule out chondrodysplasia punctata or a normal chondrodysplasia punctata 1 (CDPX1) gene without mutation. Stippling of the bones and cartilage is rarely seen after childhood. Phalangeal abnormalities are important clinical features to look for once the stippling is no longer visible. Other, more severe, clinical features include respiratory abnormalities, hearing loss, cervical spine abnormalities, delayed cognitive development, ophthalmologic abnormalities, cardiac abnormalities, gastroesophageal reflux, and feeding difficulties. CDPX1 actually has a spectrum of severity; different mutations within the CDPX1 gene have different effects on the catalytic activity of the ARSE protein. The mutations vary between missense, nonsense, insertions, and deletions. Cause
The only known cause of this condition is a mutation in the X-linked chondrodysplasia punctata 1 (CDPX1) gene.
If use of nortriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group recommends reducing the dose of nortriptyline in CYP2D6 poor or intermediate metabolizers, and selecting an alternative drug or increasing the dose in ultrarapid metabolizers. Chemistry
Nortriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene TCAs include amitriptyline (N-methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary amine TCA, with its N-methylated parent amitriptyline being a tertiary amine. Other secondary amine TCAs include desipramine and protriptyline. The chemical name of nortriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine and its free base form has a chemical formula of C19H21N1 with a molecular weight of 263.384 g/mol. The drug is used commercially mostly as the hydrochloride salt; the free base form is used rarely. The CAS Registry Number of the free base is 72-69-5 and of the hydrochloride is 894-71-3. History
Nortriptyline was developed by Geigy. It first appeared in the literature in 1962 and was patented the same year. The drug was first introduced for the treatment of depression in 1963. Society and culture
Generic names
Nortriptyline is the English and French generic name of the drug and its INN, BAN, and DCF, while nortriptyline hydrochloride is its USAN, USP, BANM, and JAN. Its generic name in Spanish and Italian and its DCIT are nortriptilina, in German is nortriptylin, and in Latin is nortriptylinum.