GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

BACKGROUND: GM1 gangliosidosis is a rare disease due to mutations in the GLB1 gene and autosomal recessive deficiency of b-galactosidase. There is considerable overlap between classical phenotypes and clinical and imaging findings, which are often difficult to interpret. PATIENT: The patient in this study had dysmorphism, dysostosis, progressive dystonia, and T2 hypointensity in the basal ganglia. Partially similar clinical and radiologic findings were described previously in two reports. CONCLUSIONS: T2 hypointensity in the globus pallidus should, in the appropriate clinical setting, lead to consideration of thediagnosis of GM1 gangliosidosis

Derivative chromosome 7 in a newborn with hypotelorism, cleft palate, agenesis of corpus callosum and semilobar holoprosencephaly

Cytogenetically visible unbalanced chromosome rearrangements involving the euchromatic regions most often result in severe phenotypic features. Often, it is not possible at microscopic level to distinguish if a chromosomal anomaly involves one or more than one chromosome. In these cases, the parents study is fundamental and is usually the first line of study. We report a female newborn with multiple anomalies. Ultrasonography at 32+6 weeks of gestation revealed moderate ventricular dilatation, microcephaly and intrauterine growth restriction (IUGR). Delivery was at 35 weeks and microcephaly, hypotelorism, complete medium cleft palate with nasal depression, agenesis of the corpus callosum, thalamic fusion and fusion of the lateral ventricles in the frontal region suggestive of semilobar holoprosencephaly (HPE) was observed. Seizures and nistagmus were described since the eighth day. Hypotonia was present. In addition, diabetes insipidus was diagnosed. Sepsis was developed at day 14 followed by death at day 18 in consequence of seizures and respiratory insuficiency. Cytogenetic analysis revealed an abnormal chromosome 7qter as a result of an unbalanced segregation of a maternal reciprocal translocation t(7;19), with breakpoints at 7q36.1 and 19q13.42. The newborn karyotype is 46,XX,der(7)t(7;19)(q36.1;q13.42)mat. The patient presented a partial trisomy of the region 19q13.42→qter and a partial monosomy of the region 7q36.1→7qter. Partial monosomy of chromosome 7qter has been characterized by a wide phenotypic manifestations, but HPE, microcephaly, midface hypoplasia, maxillary anomalies and sacral agenesis are frequently described. However, is not often reported in newborns. Partial trisomy 19q is a rare and severe condition, and has been described associated with low birth weight, growth retardation, microcephaly, seizures, dysmorphic facial features, short neck, clynodactyly, heart malformations, anomalies of the genitor-urinary and gastrointestinal tract. To our knowledge, there is only one previous case of der(7)t(7q;19q)(q36.1;q13.43) described, in a fetus who presented severe sacral agenesis and IUGR. The case herein reported presents some of the most common features of 7q36 partial monosomy and 19q terminal trisomy, although some of them are present in both conditions. The presence of those two imbalances may complicate the final phenotype but the important matter will be the counseling of the couple and to prevent future imbalances in their offspring.N/

Intrahepatic Cholestasis of Pregnancy: Risk Factor for Neonatal Respiratory Distress Syndrome?

Introdução: A colestase intra-hepática da gravidez está associada a complicações fetais e neonatais graves, incluindo síndrome de dificuldade respiratória. Tem sido recomendada terapêutica materna com ácido ursodesoxicólico e antecipação do parto para reduzir o risco de complicações. Os objetivos foram determinar a associação entre colestase intra-hepática da gravidez e síndrome de dificuldade respiratória neonatal e avaliar a relação com níveis maternos de ácidos biliares e procedimentos perinatais. Metodologia: Estudo caso-controlo incluindo grávidas com colestase intra-hepática da gravidez e respetivos recém-nascidos (grupo colestase), com parto numa maternidade portuguesa de nível III entre 2006 e 2010. Os controlos foram emparelhados para idade gestacional e peso ao nascimento (1 caso para 2 controlos). Resultados: Foram incluídas 42 grávidas com colestase intra-hepática da gravidez (incidência 0,15%) e 53 recém- -nascidos. Dez recém-nascidos do grupo colestase (19,2%) e 14 controlos (13,7%) tiveram dificuldade respiratória(p=0,375). A FiO2 máxima foi superior no grupo colestase (mediana 34,0% vs. 25,0%; p=0,294), mas sem diferença quanto à ventilação mecânica. A idade gestacional ao diagnóstico de colestase materna foi menor nos recém-nascidos com dificuldade respiratória (mediana 30,5 vs 33,5 semanas; p=0,024). A taxa de parto desencadeado iatrogenicamente(69,8% vs. 40,6%; p=0,001; OR=3,4), cesariana (66,0% vs 44,3%; p=0,01; OR=2,4) e corticoterapia pré-natal (43,4% vs. 25,5%; p=0,022) foi significativamente maior no grupo colestase. Não se encontrou relação entre dificuldade respiratória neonatal e níveis maternos de ácidos biliares nem terapêutica materna com ácido ursodesoxicólico. Conclusão: A colestase intra-hepática da gravidez, sobretudo de início precoce, está tendencialmente associada a síndrome de dificuldade respiratória neonatal. A antecipação do parto traz riscos adicionais para os recém-nascidos. A corticoterapia pré-natal neste contexto pode ter mascarado a verdadeira incidência de dificuldade respiratória neonatal