Early response to idursulfase treatment in a 3 year-old boy affected of Hunter syndrome.

We present a 3-year-old boy affected with Hunter syndrome. When we first evaluated the patient glycosaminoglycans (GAG) in urine were elevated (94.6 ng/nmol/creatinine); the enzyme activity determined in serum was decreased (3.9 nmol/hxml) and the mutation found was N350H, exon 8. His clinical signs were coarse facial features, hepatomegaly (6 cm), splenomegaly (6 cm), elbow stiffness and hypospadias; dilatation of the perivascular spaces and white matter abnormalities, mitral regurgitation. After two weeks on enzyme replacement therapy (ERT) with idursulfase (IDS), the excretion of GAG was decreased to 36.2 ng/nmol/creatinine and the liver and spleen volumes were reduced to normal limits. He was subsequently noted to have a softer, finer skin, he had no further bouts of bronchitis, and his physical activity improved. This indicates that IDS in young children is well tolerated and that it has several effects which may confer clinical benefits with long-term therapy.

Intrauterine growth retardation, duodenal and extrahepatic biliary atresia, hypoplastic pancreas and other intestinal anomalies: further evidence of the Martínez-Frías syndrome.

We describe a patient born to consanguineous parents, who presented with an MCA pattern characterized by low birth weight, duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas and intestinal malrotation. The infant died 60 days after birth. Chromosomes at 550-600 band levels were normal for a female (46,XX). This patient confirmed the autosomal recessive disorder previously described by our group. The pathogenesis of this syndrome is most probably of blastogenetic origin mainly affecting midline developmental duodenal biliary pancreatic junction.

A diagnostic conundrum: two siblings with features overlapping the Kabuki and Malpuech syndromes. A new MCA syndrome?

We report two siblings, a boy and a girl, with a constellation of anomalies that overlap the phenotypes of Kabuki and Malpuech syndromes. Both patients had a facial appearance suggestive of Kabuki syndrome, sagittal vertebral clefts, and short fifth fingers. In addition, the girl had brachydactyly of the index finger, and the boy, cleft lip and palate, mild postnatal growth deficiency, coarctation of the aorta, ventricular septal defect, patent ductus arteriosus, and a caudal appendage. The fact that this pattern of anomaly occurred in siblings, together with the presence of sparse eyebrows medially, rather than laterally, in both patients and a caudal appendage in the boy, militates against the diagnosis of Kabuki syndrome. Furthermore, the presence of a caudal appendage in a child with cleft lip and cleft palate and renal abnormalities is suggestive of Malpuech syndrome. The normal growth pattern and psychomotor development observed in both children, however, is inconsistent with this diagnosis, although they may represent a milder end of the phenotypic spectrum for Malpuech syndrome. Alternatively, we conclude that the condition may represent a distinct multiple congenital anomaly (MCA) syndrome. The occurrence of a pattern of MCA in two siblings with phenotypically normal parents and normal cytogenetic studies, including high-resolution banding and subtelomeric probes, points toward an autosomal recessive mode of inheritance. However, germinal mosaicism and other types of non-traditional inheritance, such as a defect in genomic imprinting or uniparental disomy, should also be considered.