New mutations in two Dutch patients with early infantile galactosialidosis.

Galactosialidosis is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal beta-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A (PPCA). We report the first 2 Dutch cases of early infantile galactosialidosis, both presenting with neonatal ascites. The defect was identified in urine, leukocytes, and fibroblasts.

Hepatocellular carcinoma in glycogen storage disease type IV.

A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.

Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations.

Rubinstein-Taybi syndrome (RTS) is a malformation syndrome characterised by facial abnormalities, broad thumbs, broad big toes, and mental retardation. In a subset of RTS patients, microdeletions, translocations, and inversions involving chromosome band 16p13.3 can be detected.

[Metabolic acidosis in children: the usefulness of 'anion gap'].

Metabolic acidosis occurs frequently in small children. The most common causes are hypoxia, sepsis, gastroenteritis and hypovolaemia. Calculation of the anion gap is useful in establishing the cause.

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations.

Treatment of osteogenesis imperfecta with the bisphosphonate olpadronate (dimethylaminohydroxypropylidene bisphosphonate).

Unlabelled: Osteoporosis is an important feature of osteogenesis imperfecta (OI). So far, no effective medical treatment is available. We treated three boys with severe OI type III and vertebral deformities for 5-7 years with continuous oral administration of the bisphosphonate, olpadronate.

MRI screening of kindred at risk of developing paragangliomas: support for genomic imprinting in hereditary glomus tumours.

Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing.

Oculoauriculovertebral spectrum and cerebral anomalies.

We report on three Dutch children with a clinical diagnosis of oculoauriculovertebral spectrum (OAVS) and hydrocephalus. The clinical features are compared to 15 published cases of OAVS and hydrocephalus. Several other cerebral abnormalities were present in the whole group.

beta-Glucuronidase deficiency as a cause of fetal hydrops.

Mucopolysaccharidosis type VII (MPS VII) was diagnosed in a case of severe fetal hydrops. beta-glucuronidase deficiency was demonstrated in the amniotic fluid, which was obtained at 25 weeks of gestation, and in the fibroblasts of the child, which were cultured after fetal death in the 26th week of gestation. In the amniotic fluid the two-dimensional electrophoresis pattern of glycosaminoglycans was in agreement with MPS VII.

Adult adrenoleukodystrophy: the clinical spectrum in a large Dutch family.

A large family with adrenoleukodystrophy is described and the case histories of two clinically symptomatic and related male patients are presented. Clinical, biochemical and genetic screening of their family demonstrated two clinically affected males, one biochemically affected male and five carrier females. Two women were symptomatic; one suffered an acute exacerbation.

Linkage analysis in X-linked adrenoleukodystrophy and application in post- and prenatal diagnosis.

We have performed linkage analysis with the DNA markers DXS52 and the clotting factor VIII gene (F8C), in several large families with X-linked adrenoleukodystrophy (ALD). The tight linkage to DXS52 could be extended giving a maximal LOD score of 22.5 at 1 cM.

Familial vascular retinopathy. A preliminary report.

We describe a new hereditary syndrome with an autosomal dominant mode of inheritance, with vascular retinopathy, migraine and Raynaud's phenomenon as the most striking features. The retinopathy is characterized by tortuosity and variable caliber of the retinal vessels, haemorrhages, telangiectases and both central and peripheral vascular occlusions, leading finally to a proliferative retinopathy.

[Focal dermal hypoplasia, or the Goltz-Gorlin syndrome].

A female newborn is reported with focal dermal hypoplasia (Goltz-Gorlin syndrome) presenting multiple skin and extremity-abnormalities. A short review of today's literature in relation to mode of inheritance and clinical manifestations is given.

Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory.

A study based on fifteen pedigrees showed that familial glomus tumours are inherited almost exclusively via the paternal line, a finding inconsistent with autosomal dominant transmission. The results can be explained in terms of the genomic imprinting hypothesis--the maternally derived gene is inactivated during female oogenesis and can be reactivated only during spermatogenesis. Genomic imprinting may have considerable implications for genetic counselling with respect to glomus tumours and also for the understanding of other hereditary diseases.

Werdnig-Hoffmann disease in a Nigerian infant.

A Nigerian infant with the classical features of Werdnig-Hoffmann disease is described. According to the literature the incidence in black Africans is very low. Attention is drawn to the fact that neurological illnesses are often overlooked in negroid races; several reasons are given.

Holoprosencephaly: variation of expression in face and brain in three sibs.

A family is described containing three sibs with holoprosencephaly. They showed a striking diversity of both cerebral and facial abnormalities. Autosomal recessive inheritance seems most likely.

[An infant with hereditary methemoglobinemia].

Autosomal recessive hereditary methemoglobinemia associated with mental retardation is a rare syndrome caused by a deficiency of the enzyme NADH cytochrome b5 reductase. A patient suffering from this disorder is described. The etiology of the syndrome and the (im)possibilities of treatment and prenatal diagnosis are discussed.

Dicarboxylicaciduria and secondary carnitine deficiency in glycogenosis type IV.

A 3 year old boy developed an unusually mild form of glycogen storage disease type IV. Metabolic investigations showed severe abnormalities of fatty acid and carnitine metabolism. A muscle carnitine deficiency was found.

Congenital microcephaly, infantile spasms, psychomotor retardation, and nephrotic syndrome in two sibs.

Two boys are described with congenital microcephaly, infantile spasms, psychomotor retardation and an early-onset nephrotic syndrome. The autopsy findings of one patient are described in detail. Polymicrogyria was the most prominent feature and the kidneys showed focal segmental glomerulosclerosis.