Substrate Reduction Therapy in Four Patients with Milder CLN1 Mutations and Juvenile-Onset Batten Disease Using Cysteamine Bitartrate.

Homozygous mutations in the gene CLN1 typically result in infantile-onset neuronal ceroid lipofuscinosis, a severe progressive neurological disorder with early death. The gene CLN1 encodes the enzyme palmitoyl protein thioesterase (PPT1), which is involved in lysosomal degradation of S-fatty acylated proteins. Cysteamine bitartrate (Cystagon) has been shown to reduce the storage material in PPT1 deficient cells. We report the results of a 7-year, open label, nonrandomized trial using Cystagon in four individuals with juvenile-onset NCL resulting from milder CLN1 mutations. The Cystagon doses were gradually increased with the goal of achieving 50 mg/kg bodyweight. The disease progression was monitored with parental questionnaires in four treated individuals and five untreated controls with the same CLN1 mutations. Mononuclear leukocytes from the treated individuals were examined for submicroscopic lysosomal storage inclusions. Cystagon treatment resulted in decreased storage material in peripheral leukocytes of the treated individuals. No severe side effects were noted. An allergic rash occurred in one of the individuals that required a dose reduction. The treatment did not result in overall attenuation of the disease progression. Slower progression of the disease was observed in two of the individuals when they were analyzed separately. However, slower progression in these individuals was also observed prior to starting the treatment. This effect may have been due to the higher Cystagon dose achieved in this group, but it could also have been coincidental. The apparent lack of toxicity of Cystagon may warrant further Cystagon trials in infantile NCL, possibly in conjunction with other developing therapies.

Probing the human genome in search for a new 3q syndrome.

We report a case of partial trisomy 3q syndrome which could not be clinically identified as a distinct entity. The major clinical findings include: psychomotor delay with behavioral problems, coarse facial features, frontal bossing, bushy eyebrows, prominent ears, a small upturned nose and a history of repaired inguinal hernia. There was an additional material on chromosome 4, which could easily be matched with bands 18q21.2-q22; 2p24-p25; 16p21-p23; 10p12-p14; 20q12-q13.2; 15q25-q26.2; 8p23-p24.2 and 6p22.3-p24 and a new syndrome could apparently be suggested based on GTG techniques alone. Nevertheless, by FISH technique, the extra segment was identified as a part of 3q26.3-qter. We provide an extensive review of trisomy 3q syndrome and present a caveat of the consequences of description of new syndromes based on routine banding techniques especially in situations where the origin of chromosomal abnormalities is de novo or parents are not available for cytogenetic evaluation.

The erect penis--injury prone organ.

Erection converts the safe, flaccid penis into a vulnerable organ. During erection, the usually thick tunica albuginea becomes very thin and easily fracturable. Penile fracture is an under-reported urologic injury, with only approximately 100 cases reported in the world literature. We report on three cases, one with rupture of one corpus spongiosum and two with rupture of both corpora cavernosa associated with almost complete transection of the urethra. All three cases were treated surgically, with good outcome and no postoperative complications. The authors postulate that some cases of deviation of the penis are actually the result of some minor degree of penile fracture.