RESUMO
Torrance, San Diego, and Luton types ("West coast" types) of neonatal platyspondylic short-limbed dwarfism are suspected to be caused by dominant mutations that are obligatorily lethal. We report on an affected mother, who passed the disease to her daughter, confirming dominant disease transmission. Survival of the mother indicates a wider phenotypic spectrum.
Assuntos
Nanismo/genética , Genes Letais , Nanismo/classificação , Evolução Fatal , Feminino , Humanos , Recém-NascidoRESUMO
Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.
Assuntos
Cromossomos Humanos Par 3/genética , Doenças Renais Císticas/genética , Falência Renal Crônica/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Rim/patologia , Doenças Renais Císticas/patologia , Falência Renal Crônica/patologia , Escore Lod , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Análise de SobrevidaRESUMO
Bilateral renal vein thrombosis and venous sinus thrombosis were diagnosed within 3 weeks of birth in a full-term neonate. Heterozygosity for a factor V mutation leading to resistance against the anticoagulatory properties of activated protein C was found. Heparin therapy led to resolution of the thrombotic manifestations. With long-term oral anticoagulation, no relapse or other thrombotic event occurred during infancy.
Assuntos
Transtornos da Coagulação Sanguínea/genética , Fator V/genética , Embolia e Trombose Intracraniana/genética , Mutação , Veias Renais , Trombose/genética , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Heparina/uso terapêutico , Heterozigoto , Humanos , Recém-Nascido , Embolia e Trombose Intracraniana/complicações , Embolia e Trombose Intracraniana/tratamento farmacológico , Masculino , Trombose/complicações , Trombose/tratamento farmacológicoRESUMO
Propionic acidemia is often manifested during the neonatal period with vomiting, failure to thrive, lethargy, and hyperammonemic coma when catabolism is prolonged. Mild lactic acidosis frequently accompanies metabolic decompensation. We present two patients with propionic acidemia whose initial manifestation was complicated by severe lactic acidosis caused by thiamine deficiency, which resulted from an inadequate supply of, and an increased need for, thiamine during metabolic stress. To prevent acute thiamine deficiency, we propose early vitamin supplementation during treatment of any severe metabolic decompensation accompanied by insufficient food intake.