Childhood blindness

Williams, M.L., Coleman, J.E., Haire, S.E., Aleman, T.S., Cideciyan, A.V., Sokal, I., Palczewski, K., Jacobson, S.G., and Semple-Rowland, S.L. (2006). Lentiviral expression of retinal guanylate cyclase-1 (RetGCl) restores vision in an avian model of childhood blindness. PLoS. Med. 3 e201. 

Acland GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001 28 92-95. 

On the basis of available information, however, the prevalence of childhood blindness in the United States is estimated at 0.6—6.1 per 1000 children.22 Because testing infants for visual impairments is difficult, more than 80 percent of cases of childhood visual impairment are diagnosed at ages greater than 2 years.23 In the year 2000, the prevalence of vision impairment in 8-year-old children in metropolitan Atlanta was 1.2 per 1000. Approximately one-half to two-thirds of these children with vision impairment also have one or more other developmental disabilities.24 According to the Centers for Disease Control (CDC), the prevalence of hearing loss in children 8 years old in metropolitan Atlanta in 2000 was the same as the prevalence of vision impairment 1.2 per i,ooo.2S Children born with vision or hearing deficits are, in short, more common than people think. 

Rahi, 1. S., Sripathi, S., Gilbert, C. E. and Foster, A. (1995). Childhood blindness due to vitamin A deficiency in India regional variations. Archives of Disease in Childhood, 72 (4), 330-333. 

There is well-documented evidence that clinical vitamin A deficiency is a major cause of childhood blindness and visual impairment in the heavily populated, rice-dependent areas of India, Bangladesh, Indonesia, and the Philippines. 

Vitamin A deficiency (section 11.2.4) is the single most important cause of childhood blindness in the world, with some 14 million pre-school children showing clinical signs of deficiency and 190 million people at risk of deficiency. 

From the standpoint of retinal disorders, rAAV has also demonstrated great promise in preclinical trials for Leber s congenital amaurosis (LCA). LCA is a very severe retinal degenerative disease that leads to childhood blindness. The genetic defect in LCA is the loss of a 65-kD membrane protein called RPE65. 

Cytomegalovirus (CMV) is a member of the herpes virus family, as are the varicella zoster and Epstein-Barr viruses described earlier. CMV is a common virus, and many people are infected early in the childhood. Children tend to get an asymptomatic infection, while infected young adults may develop a mono-nucleosis-like illness. Infection of a fetus is very serious and can lead to permanent brain damage or death of the fetus. In AIDS patients, CMV infection can recur and tend to infect the retinas of eyes, leading to blindness. The virus also infects the adrenal gland, leading to hormonal imbalance. CMV pneumonia in patients who have PCP at the same time is usually fatal. 

Blinded scoring of the birth records of 36 patients with COS and 35 sibling controls found no significant differences between the groups (Nicolson et ah, 1999c). Moreover, the rate of complications in the early-onset patients of the NIMH study was similar to that seen in adult-onset patients. These preliminary results, as well as the work of others (Frangou, 1999), suggest that, while obstetric complications may play a role in the development of schizophrenia in some patients, they are not more salient in childhood-onset cases. 

C. T., Lenane, M.C., Hamburger, S.D., Smith, A.K., Albus, K.F., Alaghband-Rad, J., and Rapoport, J.L. (1996) Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 53 1090-1097. 

Flament, M.F, Rapoport, J.L., Berg, C.J., Sceery, W., Kilts, C., Mells-trom, B., and Linnoila, M. (1985) Clomipramine treatment of childhood obsessive-compulsive disorder. A double-blind controlled study. Arch Gen Psychiatry 42 977—983. 

Inhibition of the MAO-A enzyme for the treatment of depression is appealing because MAO-A is specifically responsible for the degradation of serotonin and norepinephrine. There was initial interest in clorgyline for treatment of adult depression and childhood ADHD (Potter et ah, 1982 Zametkin et ah, 1985). Clorgyline was found to be beneficial in a small, double-blind, crossover study for the treatment of ADHD in children, but adverse events associated with irreversibility resulted in the lack of an industry sponsor for further trials (Zametkin et ah, 1985). 

Spencer, X, Wilens, X, Biederman, J., Earaone, S.V. Ablon, J.S. and Tapey, K. (1995) A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry 52 434—443. 

In the Zito et al. study (2000), antidepressants were the second most commonly prescribed psychotropic medication. There are a total of 10 studies or case reports in the literature examining antidepressant use in preschool children (Table 49.4). None of the 10 studies are randomized, double-blind, or placebo-controlled trials. The ten uncontrolled studies looked at a total of 37 preschool children. Six of the studies looked at a total of 29 preschoolers with autism or childhood schizophrenia (Campbell et ah, 1971a Petti and Campbell, 1975 Holttum et ah, 1994 Sanchez et ah, 1996 DeLong et ah, 1998 Hollander et ah, 2000). While these six studies are difficult to compare, given the small sample sizes and the different treatment medications, these open-label studies suggest that clomipramine, venlafaxine, and fluoxetine may be helpful to reduce some psychiatric symptoms found in autistic... 

Some of the earliest studies of psychotropic medications in preschool-age children involved neuroleptics. In autism, antipsychotics are the most frequently used psychoactive agents for the reduction of stereotypies, temper tantrums, aggressiveness against self or others, and hyperactivity (Campbell et al., 1999). There are seven studies with preschoolers with a total subject number of 59. Each of these seven studies involved medication trials with preschool children diagnosed with autism or childhood schizophrenia (Table 49.5). Only one study was a randomized, double-blind, pla-... 

Fish et ah, 1969 TFP 10 (10) 2-5 Childhood schizophrenia DSMTI criteria Independent blinded rater TFP 0.17-0.67 mg/day 4-15 weeks 8/10 improved with less disorganized speech and behavior Decreased irritability and hyperactivity 5/10 had mild EPS symptoms 1 child had a transient elevated SCOT 1/10 got worse... 

Campbell et al., 1971 MLD 10 (10) 3-5 Childhood schizophrenia DSM-II criteria Independent blinded rater MLD 1-2.5 mg/ day 6-12 weeks 6/10 improved No SEs on therapeutic doses... 

In Southeast Asia, an estimated 5 million children develop an eye disease known as xerophthalmia due to vitamin A dehciency every year. Of these, 0.25-0.5 million will eventually go blind. Vitamin A dehciency is also correlated with a weakened immune system and consequentially an increased susceptibility to potentially fatal afflictions, including diarrhea, respiratory diseases, and childhood diseases such as measles. According to statistics compiled by UNICEF, improved vitamin A nutrition could be expected to prevent approximately 1-2 million deaths a year among children aged 1-4, and an additional 0.25-0.5 million deaths during later childhood. 

In this context, Gittleman-Klein and Klein (104) conducted a double-blind, placebo-controlled study of 35 nonpsychotic, school-phobic children. They found a good response in all children given imipramine but in only 21 % of those on placebo. Because PD patients often experienced separation anxiety as children, this suggests that some cases of school phobia may be the childhood equivalent of PD, for which imipramine is effective. 

Nevertheless, this condition is responsive to treatment with dopamine-2 receptor antagonists. Hence, this condition is one of the clearest childhood indications for treatment with these medications. In theory, any dopamine-2 blocking receptor antagonist could be used. Haloperidoi has been the most extensively tested and used medication for this condition (167). The typical dose for children aged 3 to 12 years old is 0.2 mg/kg per day. More recently, in a double-blind study of 36 boys with Tourette s syndrome, risperidone was effective in reducing tics in 88% versus 60% for haloperidol (197), perhaps making risperidone a better option than a neuroleptic in terms of neurological adverse effects. 

Kumar S, Frazier JA, Jacobsen LK, et al. Childhood onset schizophrenia a double-blind clozapine haloperidol comparison. Arch Gen Psychiatry 1996 53 1090-1097. 

Bateman, B., Warner, J.O., Hutchinson, E., Dean, T., Rowlandson, P., Gant, C., Grundy, J., Fitzgerald, C., Stevenson, J. 2004. The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Archives of Disease in Childhood 89 506-511. 

---