RESUMEN
Inborn errors of fatty acid oxidation, including medium chain acyl CoA dehydrogenase (MCAD) deficiency are readily detectable and treatable metabolic disorders in which recognition of symptoms is important. Symptoms occur when there is fasting, often associated with illness. If not diagnosed, these inborn errors of metabolism can result in sudden death classified as SIDS. These disorders can be diagnosed by ordering plasma or blood spot acylcarnitine profiles.
Asunto(s)
Acil-CoA Deshidrogenasas/deficiencia , Ácidos Grasos/metabolismo , Errores Innatos del Metabolismo/complicaciones , Muerte Súbita del Lactante/etiología , Diagnóstico Diferencial , Humanos , Lactante , Masculino , Errores Innatos del Metabolismo/diagnóstico , Oxidación-Reducción , Muerte Súbita del Lactante/prevención & controlRESUMEN
A trisomy 17pter --> p11.2 derived from a supernumerary de novo satellited marker was identified by GTG bands and fluorescent in situ hybridisation (FISH) in amniocytes of a fetus with malformations and intrauterine growth retardation (IUGR). At 39 weeks a male infant with a phenotype similar to other postnatal cases of 'pure' complete trisomy 17p was born. Some additional clinical features, however, make him more severely affected than previous patients.
Asunto(s)
Cromosomas Humanos Par 17 , Enfermedades Fetales/genética , Diagnóstico Prenatal , Trisomía , Anomalías Múltiples/genética , ADN Satélite , Retardo del Crecimiento Fetal/genética , Humanos , MasculinoRESUMEN
We describe a "new" syndrome of spondylospinal thoracic dysostosis with a short curved spine and fusion of the spinous processes, short thorax with "crab-like" configuration of the ribs, pulmonary hypoplasia, severe arthrogryposis and multiple pterygia, and hypoplastic maxilla and mandible in two siblings. This appears to be an autosomal recessive lethal trait. A literature review revealed two reports of four similar or related cases.
Asunto(s)
Artrogriposis/diagnóstico por imagen , Disostosis/diagnóstico por imagen , Pterigion/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Femenino , Humanos , Recién Nacido , Radiografía , SíndromeRESUMEN
X-linked hereditary spastic paraplegias (HSP) present with two distinct phenotypes, pure and complicated. The pure form is characterized by spasticity and gait difficulties but lacks the additional features (nystagmus, dysarthria, mental retardation) present in the complicated form. The complicated form is heterogeneous, caused by mutations of the L1CAM gene at Xq28 (SPG1) or the PLP gene at Xq22 (SPG2) that is allelic to Pelizaeus-Merzbacher disease (PMD). Since in one kindred (K313) the pure form of HSP was also mapped to Xq22, this raises the issue as to whether a pure form of HSP exists that is allelic to X-linked complicated HSP (SPG2) and PMD. To answer this question, we carried out linkage analysis in a new pedigree with pure HSP (K101) and refined linkage in pedigree K313. The PLP gene was also screened for mutation by direct sequencing and reverse-transcriptase polymerase chain reaction (RT-PCR). In both families, the disease locus mapped to Xq22 with Lod scores at zero recombination of 5.3 for COL4A5 2B6 in K313 and 2.4 for DXS101 in K101. A T to C transition in exon 5 of the PLP gene was identified from affected individuals of K313. This transition causes a Ser to Pro mutation in the major extracellular loop of PLP/DM20. This finding demonstrates that a form of X-linked pure spastic paraplegia, X-linked complicated HSP (SPG2) and PMD are allelic disorders. There was no evidence of mutations in either coding sequences or the intron/exon junctions of PLP in pedigree K101, suggesting that the disease-producing mutation may be in the noncoding portions of PLP or in a nearby gene.
Asunto(s)
Apoproteínas/genética , Ligamiento Genético , Mutación , Proteína Proteolipídica de la Mielina/genética , Paraparesia Espástica Tropical/genética , Cromosoma X , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Mapeo Cromosómico , Humanos , Masculino , Persona de Mediana Edad , Sondas Moleculares/genética , Datos de Secuencia Molecular , LinajeRESUMEN
Wolf-Hirschhorn syndrome (WHS) is due to a deletion in the terminal band of 4p16.3. Among loci that have been involved in deletions are D4S98, D4S95, D4S125, D4F26, as shown by PCR typing, Southern blot hybridization, and/or fluorescent in situ hybridization (FISH). Currently, FISH detection of WHS is predicted upon the deletion of the D4F26 locus with failure to hybridize to pC847.351, a commercially available cosmid probe. A WHS patient is shown to have an interstitial deletion, by hemizygosity at D4S98 and D4S95 but not at D4F26. This suggests that the tip of 4p, specifically D4F26, is not a critical deletion site for WHS.
Asunto(s)
Cromosomas Humanos Par 4 , Trastornos del Crecimiento/genética , Discapacidad Intelectual/genética , Deleción Cromosómica , Mapeo Cromosómico , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , SíndromeRESUMEN
We report on a 3-generation family with an interstitial deletion of the short arm of chromosome 5. Varied manifestations were found among the affected individuals including microcephaly, hypertonia, and micrognathia; mental retardation was common to all affected individuals. High resolution chromosome analysis was interpreted as del(5) (pter- > p14.3::p13.3- > qter). Molecular comparison of the deletion in this family with individuals with other 5p deletions suggests that the clinical findings are due specifically to the chromosomal material deleted from 5p13.
Asunto(s)
Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 5 , Southern Blotting , Preescolar , Mapeo Cromosómico , Cromosomas Humanos Par 18 , ADN/análisis , Femenino , Humanos , Células Híbridas , Discapacidad Intelectual/genética , Masculino , Microcefalia/genética , Hipertonía Muscular/genética , TrisomíaRESUMEN
Roberts-SC phocomelia syndrome (RS) is an autosomal recessive disorder of symmetric limb defects, craniofacial abnormalities, pre- and postnatal growth retardation, and mental retardation. Patients with RS have been reported to have premature separation of heterochromatin of many chromosomes and abnormalities in the cell-division cycle. We report an infant whose clinical and radiologic findings resemble those of RS but who lacks the cytogenetic and cell division abnormalities reported in RS. This patient may represent a variant of RS or a new syndrome.
Asunto(s)
Anomalías Múltiples , Ectromelia/genética , División Celular , Labio Leporino/complicaciones , Labio Leporino/genética , Fisura del Paladar/complicaciones , Fisura del Paladar/genética , Ectromelia/complicaciones , Ectromelia/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Radiografía , Cúbito/anomalías , Cúbito/diagnóstico por imagenRESUMEN
Five of 13 patients with microphthalmia or clinical anophthalmia studied in an institution of 650 mentally retarded adults had hypogonadotropic hypogonadism. Four males had low testosterone levels and sexual infantilism, manifesting as micropenis with small testes or cryptorchidism. One female had primary amenorrhea. All 5 patients had low gonadotropin levels, confirming a hypothalamic or pituitary basis for their hypogonadism. Thyroxin, thyroid stimulating hormone, prolactin, and A.M. cortisol were also measured and were normal. All patients with hypogonadotropic hypogonadism were chromosomally normal and had variable central nervous system defects, suggesting that they comprise a heterogeneous group of disorders. Microphthalmia or anophthalmia in a mentally retarded patient is associated with hypogonadotropic hypogonadism.
Asunto(s)
Anomalías del Ojo , Hipogonadismo , Discapacidad Intelectual , Anomalías Múltiples , Adulto , Femenino , Gonadotropinas Hipofisarias/fisiología , Humanos , Hipogonadismo/fisiopatología , MasculinoRESUMEN
The Aarskog (facial-digital-genital) syndrome is an X-linked disorder in which short stature is accompanied by hypertelorism, digital anomalies, and shawl scrotum. Except for hypertelorism and blepharoptosis, ophthalmic abnormalities have been rarely noted in this condition. We examined four patients who had Aarskog syndrome and unilaterally or bilaterally decreased vision on initial examination. Three family members had V-pattern esotropia, latent nystagmus, inferior oblique overaction, and amblyopia. A fourth patient had bilateral blepharoptosis and severe astigmatism. Other ocular features included hyperopia, anisometropia, deficient ocular elevation, blue sclerae, and posterior embryotoxon. These findings underscore the need for ophthalmic examination in asymptomatic patients with Aarskog syndrome to rule out treatable causes of visual loss.
Asunto(s)
Anomalías Múltiples/patología , Enfermedades del Desarrollo Óseo/complicaciones , Oftalmopatías/congénito , Genitales Masculinos/anomalías , Deformidades Congénitas de la Mano/complicaciones , Hipertelorismo/complicaciones , Anomalías Múltiples/genética , Adulto , Ambliopía/complicaciones , Ambliopía/congénito , Ambliopía/genética , Astigmatismo/complicaciones , Astigmatismo/congénito , Astigmatismo/genética , Blefaroptosis/complicaciones , Blefaroptosis/congénito , Blefaroptosis/genética , Estatura , Niño , Preescolar , Oftalmopatías/complicaciones , Oftalmopatías/genética , Femenino , Ligamiento Genético , Deformidades Congénitas de la Mano/genética , Humanos , Hipertelorismo/genética , Masculino , Estrabismo/complicaciones , Estrabismo/congénito , Estrabismo/genética , Síndrome , Cromosoma XRESUMEN
Because alcohol has an adverse effect on zinc homeostasis, this study was designed to study if zinc content of the diet modifies the severity of fetal alcohol syndrome in a mouse model. The effect of varying zinc intake on the progeny of pregnant mice fed a liquid diet containing 15% of the calories as ethanol was studied. Prenatal mortality was higher when the mothers consumed alcohol with inadequate zinc intake. Because of the adverse effect of alcohol on zinc homeostasis and because zinc deficiency has been shown to potentiate alcohol embryopathy, one group was given zinc supplementation to four times the Recommended Dietary Allowance. Supplemental zinc above the Recommended Dietary Allowance was not protective and appeared to have an adverse effect on fetal weight and prenatal mortality. These results suggest that zinc intake should be optimized during pregnancy but that zinc supplementation above the Recommended Dietary Allowance does not reduce the incidence or severity of fetal alcohol syndrome.
Asunto(s)
Trastornos del Espectro Alcohólico Fetal/prevención & control , Zinc/administración & dosificación , Animales , Femenino , Masculino , Intercambio Materno-Fetal , Ratones , Ratones Endogámicos CBA , Estado Nutricional , Embarazo , Zinc/deficienciaRESUMEN
Fragile X syndrome is the second most common chromosomal cause of mental retardation (MR). The calculated incidence is 1/1000, making accurate and early diagnosis important for specific preventive, pharmacologic, and cognitive treatment. The timely diagnosis in males is facilitated by the characteristic phenotype and an association with autism. In contrast, in females heterozygous for fragile X, the characteristic phenotype and infantile autism are rarely reported. We present two females with cytogenetic expression of the fragile X chromosome for whom the studies were performed because of the presence of autism or prominent autistic features and a behavioral and physical phenotype consistent with fragile X syndrome. The first female, age three years, has autism, hyperactivity, echolalia, language delay, hand stereotypies, and mild MR. The characteristic phenotype was not present nor was there a family history of X-linked MR. Fragile X expression was 6% in the proband, 3% in the mother and 1% (normal) in the father. The second child, seven years old, has prominent autistic features, hyperactivity, mild MR, mild language disorder, and a family history consistent with X-linked MR. Fragile X expression was 3% in the proband and 0% in the mother. These cases support the occurrence of fragile X in autistic females and emphasize the importance of cytogenetic screening for fragile X in this high risk population. Early diagnosis of fragile X allows precise genetic counseling and more specific cognitive and pharmacologic treatment.
Asunto(s)
Trastorno Autístico/complicaciones , Síndrome del Cromosoma X Frágil/diagnóstico , Aberraciones Cromosómicas Sexuales/diagnóstico , Niño , Preescolar , Femenino , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/terapia , Humanos , Discapacidad Intelectual/etiología , Fenotipo , Factores SexualesRESUMEN
We describe a large family (K313) having 12 males affected with X chromosome-linked recessive hereditary spastic paraplegia (HSP). The disease phenotype in K313 is characterized by hyperreflexia and a spastic gait, but intelligence is normal. Carrier females have normal gait and unremarkable neurologic profiles. Eight widely spaced X-linked DNA markers were used to genotype 43 family members. In contrast to a published study of another family, in whom complete linkage of X-linked recessive HSP to distal chromosome Xq markers DXS15 and DXS52 was reported, we observed complete linkage with two DNA markers, pYNH3 and DXS17, located on the middle of the long arm of the X chromosome. These data have been combined with linkage data from a large reference panel of normal families to localize the new X-chromosome marker, pYNH3, and to provide evidence of significant locus heterogeneity between phenotypically distinct forms of X-linked recessive HSP.
Asunto(s)
Ligamiento Genético , Variación Genética , Paraplejía/genética , Cromosoma X , Adulto , Bandeo Cromosómico , Mapeo Cromosómico , ADN/genética , Femenino , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Espasticidad Muscular/genética , LinajeRESUMEN
The myotubular myopathies are a heterogeneous group of muscle disorders in which x-linked, autosomal recessive, and autosomal dominant inheritance have been reported. Female carriers of x-linked myotubular myopathy have been reported to have abnormal muscle biopsies. We report a woman who had a normal muscle biopsy but who had 2 sons with myotubular myopathy by different fathers, indicating that a normal muscle biopsy of the mother cannot exclude x-linked inheritance. The quantity of fetal activity correlated with the severity of the disorder in this pedigree.
Asunto(s)
Ligamiento Genético , Músculos/patología , Enfermedades Musculares/genética , Cromosoma X , Adulto , Biopsia , Femenino , Heterocigoto , Humanos , Recién Nacido , Masculino , LinajeRESUMEN
Because alcoholism has adverse effects on zinc nutrition and many pregnant women consume less than the recommended dietary allowances of zinc, we postulated that zinc deficiency acts as a co-teratogen with alcohol in the fetal alcohol syndrome. We compared the effects of alcohol on progeny of pregnant mice fed a zinc-deficient diet compared to those fed a diet with adequate zinc. Pregnant CBA mice (n = 66) were fed the Lieber-DeCarli liquid diet with 0, 15, or 20% ethanol-derived calories containing 0.3 (low) or 8.5 (high) micrograms zinc/ml. Dams were sacrificed on day 18 of gestation. Resorptions, malformations, and individual fetal weights were recorded. Analysis of fetuses included assays for zinc, assessment of soft tissue malformations, and alizarin red staining for skeletal malformations. Fetal weights were lower in the groups fed the zinc-deficient diet for each concentration of alcohol (p less than 0.005). The groups fed the combination of low zinc plus alcohol had 37-52% resorptions, while the animals on the zinc-deficient diet without alcohol or the high zinc diet with alcohol had 0-2% resorptions. Skeletal malformations were related to alcohol concentration but not zinc intake, while external malformations were higher in those maintained on the low zinc-ethanol diet. These results suggest that zinc deficiency potentiated the teratogenic effects of alcohol and that nutritional intervention for alcoholic women during pregnancy might reduce the incidence or severity of fetal alcohol syndrome.
Asunto(s)
Etanol/efectos adversos , Trastornos del Espectro Alcohólico Fetal/etiología , Zinc/deficiencia , Anomalías Múltiples/inducido químicamente , Anomalías Múltiples/etiología , Anomalías Múltiples/patología , Animales , Dieta , Implantación del Embrión/efectos de los fármacos , Etanol/sangre , Femenino , Trastornos del Espectro Alcohólico Fetal/patología , Reabsorción del Feto , Feto/metabolismo , Ratones , Ratones Endogámicos CBA , Embarazo , Zinc/metabolismoRESUMEN
A patient with Silver-Russell Syndrome with previously undescribed absence of two fingers plus syndactyly of the opposite hand is reported.