Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV).

BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity. OBJECTIVE: To identify the molecular bases of different neuromuscular forms of GSD-IV and to establish possible genotype/phenotype correlations. METHODS: Eight patients with GBE deficiency had different neuromuscular presentations: three had fetal akinesia deformation sequence (FADS), three had congenital myopathy, one had juvenile myopathy, and one had combined myopathic and hepatic features. In all patients, the promoter and the entire coding region of the GBE gene at the RNA and genomic level were sequenced. RESULTS: Nine novel mutations were identified, including nonsense, missense, deletion, insertion, and splice-junction mutations. The three cases with FADS were homozygous, whereas all other cases were compound heterozygotes. CONCLUSIONS: This study expands the spectrum of mutations in the GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically and genetically heterogeneous.

Expression of the alpha4 isoform of the nicotinic acetylcholine receptor in the fetal human cerebral cortex.

Nicotinic acetylcholine receptors are likely to play an important role in neuronal migration during development. Furthermore, the alpha4 receptor subunit gene is related to a hereditary juvenile form of epilepsy. Only little information is available, however, on the expression of cerebrocortical nicotinic acetylcholine receptors during human fetal development. Using non-isotopic in situ hybridization and immunohistochemistry, we have studied the distribution of the alpha4 subunit of the nicotinic acetylcholine receptor mRNA and protein in the human frontal cortex at middle (17-24 weeks of gestation) and late (34-42 weeks of gestation) fetal stages. Both, alpha4 receptor mRNA and alpha4 receptor protein were observed beginning during week 17-18 of gestation. At this time of development, a few weakly labeled mRNA-containing cells were present mainly in the ventricular zone, the subplate and the cortical plate. A similar distribution pattern was found for the receptor protein. Around week 38 of gestation, the distribution in the cerebral cortex of alpha4 subunit-containing cells was similar to that of adult human cortices with the highest densities of labeled neurons found in layers II/III, followed by layers V and VI. Nicotinic acetylcholine receptor-containing neurons appear rather early in human fetal development. Given functional maturity, they may interact during cortical development with acetylcholine released from corticopetal fibers or other yet unknown sources subserving the process of neuronal migration and pathfinding.

[Pilomatrixoma often not identified as such]. / Pilomatrixoma veelal niet als zodanig herkend.

OBJECTIVE: To inventory incidence, diagnosis and treatment of pilomatrixoma. DESIGN: Retrospective. METHOD: Patients treated in the period 1984-1996 in the department of Surgery of the Medical Spectrum Twente, Enschede for a pilomatrixoma were traced via the Dutch Automatic Morbid-Anatomical Records Office (PALGA). Data were collected by status study. Also, the patients or their parents were interviewed by telephone about recurrences. RESULTS: Forty-eight patients with 54 pilomatrixomas had been treated. The ages varied from 2 to 77 years, 14 patients were younger than 14 years. The correct diagnosis had been made preoperatively in 11 patients (20%) in four of whom (7%) the manifestation was not the first one. In many cases (69%), the condition was mistaken for an atheromatous cyst, in children as well (in 47% of the cases). The pilomatrixoma was localized in the head and neck area 25 times, in eight of these in the parotid region. Owing to incorrect interpretation of the abnormality, three children with a pilomatrixoma in the head and neck area underwent a more radical operation than necessary. CONCLUSION: The clinical diagnosis was frequently missed. In cutaneous tumours occurring in children or localized in the head and neck area the diagnosis of pilomatrixoma should be considered.

Retractile mesenteritis: to treat or not to treat.

Retractile mesenteritis is a rare entity characterized by an inflammatory process of the mesenteric adipose tissue. The disease usually presents with abdominal pain or a palpable abdominal mass. In the majority of cases, the disease is self-limiting and the prognosis is favorable. In this paper we describe a patient who presented with a 7 x 8 cm mass in the left upper abdomen, nausea and pain in the lower back. Symptomatic treatment was given with good result. The literature on different therapeutic intervention is briefly discussed.

An important role for chromosome 17, band q25, in the histogenesis of alveolar soft part sarcoma.

A cytogenetic study of two cases of alveolar soft part sarcoma showed near-diploid karyotypes with multiple chromosomal rearrangements. An abnormality of the long arm of chromosome 17, involving band q25, is present in both cases and in 2 of 4 cases in the literature. This recurrent structural abnormality probably plays an important role in the histogenesis of this unusual neoplasm and therefore is important for further molecular investigation.

A congenital variant of glycogenosis type IV.

Three related patients are described with glycogenosis type IV with an unusual clinical presentation resulting in perinatal death. Stored material showed birefringent Maltese crosses and was present in skeletal muscles, heart, central nervous system, and liver. Muscular dysfunction resulted in a fetal hypokinesia sequence with arthrogryposis and lung hypoplasia. A subdivision of glycogenosis type IV in four subtypes is proposed, based on age of onset. Measurement of the enzyme activities in different tissues does not permit, at the moment, a distinction between the subtypes.

Familial holoprosencephaly, heart defects, and polydactyly.

We describe a pair of sibs with microcephaly, hypoplastic nose, cleft lip/palate, a complicated Fallot-like cardiac defect, and holoprosencephaly and polydactyly. One sib appeared to have normal chromosomes. The healthy parents were second cousins. This constellation of signs has been described before in at least 14 other patients, and was possibly present in several others. Although there is overlap with a number of similar conditions, especially hydrolethalus syndrome, this probably represents a separate entity. Three pairs of sibs and consanguinity in 3 families point to autosomal recessive pattern of inheritance.

Routine perinatal postmortem radiography in a peripheral pathology laboratory.

Routine postmortem radiography was done in 234 consecutive perinatal autopsies. Using ossification centre appearance and length of femoral shafts as variable it was a very useful and dependable method for estimating gestational age and intrauterine growth. In this way important conclusions can be drawn as to the reason for intrauterine growth deviations. Also many, sometimes diagnostic, abnormalities can be found.

So-called primitive neuroectodermal tumor in macerated fetuses: a confusing artifact.

We studied 11 macerated fetuses with so-called primitive neuroectodermal tumors. Because we doubled the tumorous nature of this disorder, we produced a similar lesion in a comparable 12th fetus. Experimental compression of the skull of the macerated fetus resulted in expulsion of the nervous tissue by way of the vertebral canal and into the retroperitoneal space along the peripheral nerves, with spreading into the adjacent tissues and in blood vessels. The macroscopic and microscopic picture that was induced was essentially identical to that of the 11 spontaneous cases. This lesion, which has been called primitive neuroectodermal tumor in macerated fetuses, must therefore be considered an artifact.