Abstract Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2- Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase® (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase® (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.

RESUMO Hipotricose com distrofia macular juvenil (HDMJ) é uma doença autossômica recessiva rara caracterizada por rarefação capilar por alteração nos folículos pilosos e degeneracão progressiva da retina levando a cegueira na segunda e terceira década de vida. Associada a mutações no gene CDH3, resultando em expressão anormal de P-caderina. Mutações no gene CDH3 estão relacionados à displasia ectodérmica, ectrodactilia e distrofia macular. Neste relato descrevemos um menino Iraniano de 11 anos de idade, com ausência da unha na mão esquerda e rarefação capilar desde o nascimento, e que posteriormente apresentou alterações pigmentares maculares. Teste genético do gene CDH3 revelou uma variação homozigótica no exon 6 (640A>T). Essa mutação in-frame troca uma lisina por um codon de parada prematura, alterando a síntese da proteína P-caderina no cromossomo 16q22.

ABSTRACT Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair caused by hair follicle abnormalities as well as progressive retinal degeneration leading to blindness in the second or third decade of life. It is associated with mutations of the cadherin 3 (CDH3) gene, which result in abnormal expression of P-cadherin. Mutations in CDH3 are related to ectodermal dysplasia, ectrodactyly, and macular dystrophy. In this report, we describe an 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes. Genetic testing of the CDH3 gene revealed a homozygous gene variant at exon 6 (640A>T). This novel in-frame mutation converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.

RESUMO Glaucoma é uma neuropatia óptica progressiva, caracterizada pela perda de células ganglionares e seus axônios. O principal fator de risco que leva à perda de campo visual relacionada ao glaucoma é a elevação da pressão intraocular (PIO) e vários estudos mostraram que a redução da pressão intraocular diminui o risco de progressão do glaucoma. Atualmente, uma nova classe de drogas hipotensoras foi desenvolvida e tem sido cada vez mais estudada, os inibidores da Rho-Kinase. Essas drogas reduzem a pressão intraocular aumentando a drenagem de humor aquoso através da via de drenagem primária do humor aquoso no olho, a malha trabecular. Além de aumentar o escoamento pela malha trabecular, inibidores da Rho-kinase também aumentam a sobrevivência das células ganglionares retinianas após isquemia e aumentam o fluxo ocular sanguíneo.

ABSTRACT Glaucoma is a progressive optic neuropathy characterized by the loss of ganglion cells and their axons. A major risk factor for glaucomatous visual field loss is elevated intraocular pressure (IOP), and several studies have shown that lowering IOP reduces the risk of glaucomatous progression. Currently, an increasing number of researches involve Rho kinase inhibitors, which are a new pharmacological class of hypotensive agents specifically targeting the diseased trabecular outflow pathway. Rho kinase inhibitors reduce IOP by increasing aqueous humor drainage through the primary outflow pathway in the eye, which is known as the trabecular meshwork. In addition to improving the outflow facility of the trabecular meshwork, Rho kinase inhibitors also enhance retinal ganglion cell survival after ischemic injury and increase ocular blood flow.