Self-mutilation

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

The outlook for patients who are treated at an early age is favorable. Affected babies are normal at birth but almost all will be impaired unless they receive dietary restriction by age 3 months. Mass screening has largely eliminated the untreated PKU phenotype of eczema, poor growth, irritability, musty odor (caused by phenylacetic acid) and tendency to self-mutilation. Progressive motor dysfunction has been described in children with longterm hyperphenylalaninemia. 

In many cells, the capacity for de novo synthesis to supply purines and pyrimidines is insufficient, and the salvage pathway is essential for adequate nucleotide synthesis. In patients with Lesch-Nyhan disease, an enzyme for purine salvage (hypoxanthine guanine phosphoribosyl pyrophosphate transferase, HPRT) is absent. People with this genetic deficiency have CNS deterioration, mental retardation, and spastic cerebral palsy associated with compulsive self-mutilation, Cells in the basal ganglia of the brain (fine motor control) normally have very high HPRT activity. These patients also all have hyperuricemia because purines cannot be salvaged. 

A marked increase in the plasma concentration of urate has been linked to a neurological disorder. Lesch-nyhan syndrome which is characterise by mental retardation and a compulsive form of self-mutilation (Chapter 20). 

Patients with Lesch-Nyhan syndrome experience gout-iike episodes of joint pain and kidney stones as weii as severe neurologic problems, including self-mutilation, spastic movements, and mental retardation. 

There is no perfect system for identification of animals. Tattoos and color codes frequently fade and may need to be redone after 3 to 5 months. Toe clips and ear punches are occasionally obliterated by self-mutilation or mutilation by cage mates. Ear tags and collars fall off and need to be replaced. Cage cards can be lost or destroyed. Whatever system or combination of systems of animal identification are selected by a laboratory, the shortcomings of the selected sys-tem(s) must be recognized, and procedures must be developed to address those shortcomings. 

Opioid Psychic numbing, chemical abuse and/or dependency, self-mutilative behaviors... 

Opioid antagonists have been used with mixed results in adults with PTSD. No clinical trials with these agents have been published in children and adolescents with PTSD. The opioid antagonists such as naltrexone may have limited utility in treating debilitating self-mutilative behavior and perhaps in reducing substance abuse comorbidity in adolescent patients with PTSD. 

BPD is characterized by a pervasive pattern of unstable affect, stormy interpersonal relationships, and behavioral dyscontrol. An estimated 1% to 2% of the general population manifest this syndrome. It is also a co-morbid condition with major mood disorders (i.e., different studies estimate from 25% to 75% of these patients have a major depression and 5% to 20% a bipolar disorder). Furthermore, as many as 25% of bulimics may also suffer from BPD, and approximately 70% of BPD patients abuse alcohol or drugs. Self-mutilation, suicide attempts, and completed suicides are all too frequent. Indeed, it is estimated that 3% to 10% of these patients will take their own lives. 

In an open study of 11 patients with typical borderline personality, Schulz et al. ( 253) found substantial improvement with olanzapine, particularly in psychosis, but also in anergia, hostility, and interpersonal sensitivity. Szigethy and Schulz ( 254) reported improvement in one patient whose BPRS went from 46 to 28 with risperidone. Remission of self-mutilation has also been reported in one borderline patient undergoing treatment with risperidone, as well as an SSRI, for depression (255). This patient was then able to return to a full-time job. Although one should reserve judgment until more definitive studies are completed, the more favorable side effect profile of risperidone and olanzapine suggests that these drugs may be useful when psychotic or near psychotic symptoms are present. 

Patients with this disorder not only have a disturbed eating pattern but also problems with impulse control, often resulting in drug or alcohol abuse, self-mutilation, kleptomania, and sexual disinhibition. They also may have symptoms of obsessive-compulsive disorder or obsessive-compulsive personality disorder ( 498). In these individuals, manipulation of food is associated in varying degrees with alcohol and drug abuse. They are typically poor candidates for pharmacotherapy and, not surprisingly, have been unresponsive to a variety of psychotropics. 

Chengappa KN, Ebeling T, Kang JS, et al. Clozapine reduces severe self-mutilation and aggression in psychotic patients with borderline personality disorder. J Clin Psychiatry 1999 60 477-484. Frankenburg FR, Zanarini MC. Use of clozapine in nonschizophrenic patients. Harvard Rev Psychiatry 1994 2 142-150. 

Khouzam HR, Donnelly NJ. Remission of self-mutilation in a patient with borderline personality during risperidone therapy. J NervMentDis 1997 185 348-349. 

A condition known as Lesch-Nyhan syndrome is one of the primary causes of gout. An X-linked recessive trait occurring in males, this condition involves a tremendous overproduction of uric acid due to a deficiency of one of the enzymes involved in purine metabolism, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Other abnormalites lead to mental retardation and aggressive behavior. An obvious symptom of the condition is self-mutilation. 

This results in the excessive production of uric acid, plus characteristic neurologic features, including self-mutilation and involuntary movements. 

Lesions on the lips of Lesch-Nyhan patients caused by self-mutilation. 

A serious genetic disorder is associated with the salvage pathways, the Lesch-Nyhan syndrome. It is believed that it is caused by a failure to control the de novo purine biosynthetic pathway. In the Lesch-Nyhan syndrome, the enzyme HGPRTase is severely depressed. Because the de novo pathway is controlled largely via feedback effects of purine nucleotides, the pathway is derepressed and excessive quantities of purine nucleotides and their degradation product, uric acid, are accumulated. This results is neurologic effects, self-mutilation, and mental retardation. 

In some diseases, excessive amounts of purines are produced in the body, leading to accumulation of urate. Patients with Lesch-Nyhan syndrome lack the enzyme hypoxanthine-guanine phosphoribosyltransferase (HG-PRTase). Children born with this disorder are mentally retarded and prone to self-mutilation. They produce excessive amounts of purines due to accumulation of P-Rib-PP which stimulates the first enzyme of the pathway, amido PRTase (Fig. 15-16). The excess purines are degraded via the reactions... 

The Lesch-Nyhan syndrome is a distressing disorder that includes neurological abnormalities, self-mutilation, and overproduction of uric acid. Why is uric acid overproduced ... 

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