Clinical phenotype of desmosterolosis.

We describe a child with lethal multiple malformations and generalised accumulation of desmosterol. The infant had macrocephaly, a hypoplastic nasal bridge, thick alveolar ridges, gingival nodules, cleft palate, total anomalous pulmonary venous drainage, ambiguous genitalia, short limbs, and generalised osteosclerosis. Gas chromatography-mass spectrometry demonstrated an abnormal accumulation of desmosterol in kidney, liver. and brain. Higher than normal levels of the same sterol were detected in plasma samples obtained from both parents. The biochemical phenotype in this infant is highly suggestive of a novel inborn error of cholesterol biosynthesis caused by an autosomal recessive deficiency of 3betahydroxysterol-delta24-reductase. A phenotypic overlap of this case with Raine syndrome was noted; however, desmosterol accumulation was not found on postmortem tissue samples from a previously reported case of this disorder.

Nodular fasciitis of the nose in a child.

Nodular fasciitis is an unusual benign tumour composed of fibroblasts. It presents as a rapidly growing mass arising from subcutaneous or deep fascia. Less than 20% of cases occur in children. Diagnosis can only be made by histopathological examination of a biopsy of the lesion. A case of nodular fasciitis presenting as a mass arising from the right nasal cavity in a 19-month-old female is presented. The lesion was successfully eradicated by surgical removal. There has been no recurrence at 4-year review. Nodular fasciitis is a benign condition that may mimic malignancy clinically and histologically. Recognition of this condition is important to avoid unnecessarily aggressive treatment. Relevant clinical, radiological and histological features are discussed.

Hepatobiliary disease in cystic fibrosis patients with pancreatic sufficiency.

Focal and multilobular biliary cirrhosis are considered pathognomonic of cystic fibrosis (CF) and almost invariably have been reported in patients with steatorrhea. In contrast, patients with pancreatic sufficiency and normal absorption are considered less likely to develop liver or biliary tract problems. The authors report three patients with CF and pancreatic sufficiency, presenting with recurrent abdominal pain (unrelated to pancreatitis). All had common bile duct disease, one with multilobular cirrhosis and portal hypertension. Pancreatic sufficiency was proven by quantitative pancreatic stimulation tests, 3-day fecal fat analyses, and serum pancreatic isoamylases. All three patients had mild lung disease. Two were homozygous for the common delta F508 mutation, and the other, a delta F508 compound heterozygote. Hepatobiliary structure and function were determined by serial hepatobiliary scintigraphy, percutaneous transhepatic cholecystography, and biochemical liver function tests. Patients 1 and 3 had mild hepatomegaly, normal liver biochemistry, and distal common bile duct strictures. Patient 2 had a firm nodular liver with splenomegaly, abnormal liver biochemistry, and a cholangiographic appearance of sclerosing cholangitis. All have undergone operative treatment for persistent abdominal pain. These cases confirm the occurrence of common bile duct pathology and liver disease in patients with CF and pancreatic sufficiency. They demonstrate that liver and biliary tract disease can occur independently of the underlying disease severity and the presence of steatorrhea. Further, they suggest that obstruction of the biliary tract may be an additional factor in the evolution of liver disease in CF.

Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes.

New distinct lethal osteosclerotic bone dysplasia (Raine syndrome).

We report a third case of a rare neonatal lethal sclerotic bone disorder with distinct craniofacial anomalies and striking radiographic and hitherto undescribed histopathologic features. The remarkable similarity between our patient and 2 recently reported infants suggests strongly a distinct entity. We propose the term Raine syndrome as a convenient identification of this disorder.

Intraocular lacrimal gland choristoma.

There have been nine previously reported cases of intraocular lacrimal gland choristoma. This case report is of an infant with an intraocular lacrimal gland choristoma which was managed conservatively for a 19-month period until the onset of glaucoma. Tumour biopsy was initially performed because until this time the tumour's behaviour suggested it was not malignant. The latter was confirmed on biopsy, however hypotony resulted following the surgical intervention.

Juvenile hyaline fibromatosis: an expanded clinicopathologic spectrum.

A female infant had the typical cutaneous and soft tissue lesions of juvenile hyaline fibromatosis with the characteristic histologic and ultrastructural features of the disease. Her clinical course and autopsy findings strongly resembled those of infantile systemic hyalinosis, suggesting that the two conditions may be parts of a spectrum.

Cramps following exercise.

A 13-year old boy presented with a 10-year history of severe muscle cramps experienced an hour after prolonged exercise. There was no history of exercise intolerance or myoglobinuria. A muscle biopsy showed a lipid myopathy and a deficiency of muscle carnitine palmityl transferase. He has responded to a high carbohydrate, low fat diet with added carbohydrate intake preceding extensive exercise. Diagnosis of this entity before an episode of rhabdomyolysis is unusual.

Liver disease and common-bile-duct stenosis in cystic fibrosis.

To determine the incidence of common-bile-duct lesions and their relation to liver disease in cystic fibrosis, we performed hepatobiliary scanning in 50 of 61 patients with cystic fibrosis who had hepatomegaly, abnormal liver function, or both and in 31 of 92 patients with cystic fibrosis who did not have hepatomegaly or abnormal liver function. Ninety-six percent of the patients with liver disease had evidence of biliary tract obstruction, which was defined cholangiographically as a stricture of the distal common bile duct in the majority of cases. All the patients without liver disease had normal intrahepatic and common-duct excretion of tracer. Abdominal pain was significantly more common in patients with common-duct obstruction (P less than 0.001), and enlarged gallbladders occurred only in such patients. Since fasting levels of serum bile acids were elevated in nearly half these patients, irrespective of the severity of their liver disease, serum bile acids may be markers of the severity of the common-duct lesion. We conclude that strictures of the distal common bile duct are common in patients with cystic fibrosis and liver disease. This association requires further study, since surgical relief of common-duct obstruction may prevent or ameliorate the hepatic complications of cystic fibrosis.

Congenital agastria.

Congenital agastria has never before been reported. Congenital microgastria is rare but is well documented. We have cared for a Melanesian child in whom there was no radiological, anatomical, or physiological evidence of either a rudimentary stomach or a pylorus. The esophagus joined the first part of the duodenum directly. At this esophago-duodenal junction there was microscopic evidence of fundic-type gastric mucosa. The intestine was normally rotated and there was a functioning spleen. The child also had a severe micrognathia and a cleft soft palate and required a tracheostomy to relieve upper airway obstruction. The combination of micrognathia and agastria presented a difficult nutritional delivery problem. A jejunal pouch was constructed and placed between the esophagus and duodenum to provide some storage capacity. The child grew and developed well for almost 3 years. He suffered three episodes of severe acute enteritis, probably related to lack of the protective acid-pepsin barrier against ingested microorganisms. Unfortunately, the third episode of acute enteritis caused his death 3 months after returning home to his own country.

Geleophysic dysplasia--acromicric dysplasia with evidence of glycoprotein storage.

"Geleophysic" dysplasia is a rare autosomal recessive disorder, probably of glycoprotein metabolism, which shares some clinical and roentgenological manifestations with acromicric dysplasia. We report the clinical, radiological, and pathological data of a patient with the typical picture of progressive growth delay; mild facial anomalies; small, abnormal hands; hepatosplenomegaly; and progressive cardiac valvular lesions. Electron microscopy of a liver biopsy showed similar and additional changes to those published previously.

Wilson's disease in childhood. A plea for increased awareness.

Wilson's disease, a hepatic-based metabolic disease, is treatable with a relatively good prognosis if diagnosed before severe complications occur. It has been diagnosed in eight children (five boys, three girls) in 11 years at our institution. The presenting symptoms were hepatic in four children, neurological in one and non-specific in one, whereas two children were asymptomatic siblings of index patients. The mean age at diagnosis was 8.9 years (range, 4.7-11.7 years). Two boys died soon after diagnosis: one had fulminating hepatic failure and the other, who had neurological disease, died of aspiration pneumonia. Six children are well, with regression of clinical disease, two to 10 years after the initiation of chelation therapy by mouth. The diagnosis was delayed for all symptomatic patients because of the disease's rarity, its nonspecific early manifestations and a low index of suspicion for the disease on the part of physicians.

Salivary gland choristoma of the middle ear.

A 5-year-old female with a so-called "salivary gland choristoma" in the middle ear is reported, believed to represent the nineteenth such case in the literature. The nineteen cases are reviewed. The only consistent symptom was deafness. Aural discharge, tinnitus and otalgia occurred occasionally. The findings included a middle ear mass, conduction deafness and sometimes facial and external ear developmental disorders. At surgery a lobulated firm mass in the posterosuperior tympanum was usually found, being mobile and often pedunculated from a dehiscent part of the horizontal facial nerve. Ossicular and outer ear developmental abnormalities were common.

Striatonigral degeneration.

Striatonigral degeneration is a relatively uncommon form of parkinsonism. It is clinically characterized by greater debility and a relatively rapid course, often with other superimposed extrapyramidal signs and a poor response to L-dopa. Pathologically it si a multi-system degeneration of the central nervous system, dominated by atrophy of the neostriatum with striking putaminal pigmentation. The clinical and pathological features of this condition are illustrated with a case report and the entity as a nosologic problem is discussed in the light of a review of the literature. The pathogenesis of this condition and its position among the degenerative disorders of the nervous system remain unelucidated.