Lethal form of chondrodysplasia punctata with normal plasmalogen and cholesterol biosynthesis.

We present a male autopsied case of chondrodysplasia punctata with abnormal face, symmetrical proximal limb shortness, severe psychomotor developmental delay, respiratory muscle weakness, and death at the age of 2 years. Although his clinical manifestations were similar to those of rhizomelic chondrodysplasia punctata (RCDP), biochemical studies using skin fibroblasts did not document the peroxisomal dysfunction described in RCDP. In addition, the sterol profile, for which abnormalities have recently been reported in cases of X-linked dominant form chondrodysplasia punctata (CDPX2), was normal both in the liver and in the fibroblasts. This patient may represent a new lethal form of chondrodysplasia punctata.

Reversible frontal lobe syndrome associated with influenza virus infection in children.

Two patients, a 3-year-old female and a 1-year-old female, both with a focal encephalopathic process associated with influenza A virus infection, are reported. Both children had neuropsychologic signs suggesting frontal and limbic dysfunction, without disturbances of consciousness or motor function, and had good recoveries. The results of single-photon emission computed tomography and electroencephalography support the finding of reversible impairment of the frontal and limbic areas. Focal reversible encephalopathy has rarely been reported in association with influenza virus infection, although it often provokes diffuse encephalopathies, with a poor prognosis.

Encephalomyelitis subsequent to mycoplasma infection with elevated serum anti-Gal C antibody.

We report a 7-year-old girl with acute disseminated encephalomyelitis subsequent to a mycoplasma infection. She manifested a prolonged state of akinetic mutism, during which EEG revealed well-synchronized spindles. Four months later, she regained consciousness, with no mental deficit, but complete flaccid quadriplegia persisted and magnetic resonance imaging disclosed extensive destruction of the spinal cord. Antibody against galactocerebroside was detected in her serum during the acute phase. The anti-Gal C antibody is suggested to be involved in the pathogenesis of immune-mediated demyelinating diseases in the central nervous system subsequent to mycoplasma infections.

[Parasagittal cerebral injury in perinatal asphyxia].

It is suggested that parasagittal cerebral injury in the asphyxiated full term infant may be common. However, parasagittal cerebral injury is rarely diagnosed in the neonatal period. It is said that cranial ultrasonography and CT scan are not useful to identify this lesion. Recently, it is considered that some of the intellectual deficits and behavioral problems in children at school age may have their origin in perinatal parasagittal cerebral injury. We described a patient with parasagittal cerebral injury demonstrated by CT scan. Infants with neurological abnormalities which include weakness or abnormal muscular tone of proximal upper limbs suggest parasagittal cerebral injury. CT scan obtained between 1 and 3 weeks of life is considered to be useful for the diagnosis. Early diagnosis and follow-up of parasagittal cerebral injury may lead to the understanding of frequency, prognosis and pathogenesis and to its prevention.

Neonatal hepatitis and extrahepatic biliary atresia in the same sibship.

An instance of the rare occurrence of neonatal hepatitis and extrahepatic biliary atresia in the same sibship is reported. The older brother with neonatal hepatitis developed jaundice at the age of 4 days and had clay-colored stools from early infancy. Cholangiography by exploratory laparotomy at the age of 3 months showed a normal bile duct pattern. After laparotomy, jaundice rapidly disappeared, and stools became yellow. His liver function has been normal since age 6 months to the present (6 years old). The younger brother developed jaundice and clay-colored stools at the age of 1 month. The diagnosis of extrahepatic biliary atresia was made at laparotomy at the age of 4 1/2 months. Hepatojejunostomy was performed with successful bile drainage, although he had frequent attacks of ascending cholangitis since operation. These cases support a recent hypothesis that neonatal hepatitis and extrahepatic biliary atresia may be produced by the same disease process.

Neuropathology of chronic vitamine E deficiency in fatal familial intrahepatic cholestasis.

A progressive neuromuscular syndrome developed in a girl suffering from fatal familial intrahepatic cholestasis (Byler disease). The neuromuscular syndrome included muscular wasting of the legs, pes cavus, areflexia, decreased vibratory sensation, cerebellar symptoms, ophthalmoplegia, and visual disturbance with retinitis pigmentosa. The serum vitamin E level was extremely low. Postmortem neuropathologic study revealed the following lesions: (1) Systemic axonopathy involving the peripheral nerves and proximal axons of the dorsal root ganglia and posterior roots as well as the distal axons of the central nervous system (CNS) (2) Neuronal loss in the sensory and oculomotor nuclei of the brain stem, basal ganglia, Clarke's column, posterior horn, and dorsal root ganglia. (3) Neuronal lipofuscinosis. Axonopathy was severer in the more distal axonal segments, although the cuneate fasciculus was more affected than the gracile fasciculus. The severity of neuronal lipofuscinosis was not correlated with that of neuronal disintegration. The electron-dense bodies in the dystrophic swollen axons resembled lipofuscin granules. These neuropathologic lesions were considered to be the sequelae to chronic vitamin E deficiency.

Menkes' kinky hair disease: morphological and immunohistochemical comparison of two autopsied patients.

An autopsied patient with Menkes' kinky hair disease, who showed unusually long survival until the age of five years with typical neuropathological changes, was examined for distribution of neuronal depletion in the cerebral cortex, and the cerebellar changes were compared morphologically and immunohistochemically with those found in a younger patient (1 year 8 months old) reported previously. Neuronal loss in the cerebral cortex in the both cases, which was ill-defined and unassociated with gliosis, was preferentially distributed in the fifth and sixth layers, especially of the gyral bottom in almost all lobes in the older case. Therefore, this change was thought to be secondary to local ischemia caused by mechanical distortion at the stage of gyrus formation in addition to abnormal development. Ultrastructurally, a prominent increase of confronting cisternae (CC) complexes was found in the perikaryon and processes of Purkinje cells in both cases, and in the older patient CC complexes were arranged more densely and were transformed into concentric lamellar structures in the swollen dendrites. Immunohistochemically, the stainability of neurofilaments (NF, 200 kDa) in Purkinje cells, with or without somatic sprouts was faint or negative in the older patient compared with the marked or moderate positivity in the younger patient and age-matched controls. Empty baskets were absent and NF-positive axonal terminals and synaptophysin-positive granules on Purkinje cells were markedly decreased in both cases. These changes suggest that Purkinje cells degenerate progressively with time and that basket cells also are simultaneously involved.

Repetitive monomorphic ventricular tachycardia in a 4-year-old boy with toxic multinodular goiter.

A case of toxic multinodular goiter associated with repetitive monomorphic ventricular tachycardia (VT) is reported. A 4-year-old boy was found to have asymptomatic VT. When treatment with antiarrhythmic agents turned out to be ineffective, thyrotoxicosis was suspected due to the rapid enlargement of the left thyroid gland and associated thyroid function studies. A diagnosis of toxic multinodular goiter was made on the basis of subsequent scintigraphy and ultrasonography. Treatment with antithyroid drugs and inorganic iodine restored the thyroid function to normal, and was accompanied by the disappearance of VT. A left thyroid lobectomy was performed, and the pathological findings were compatible with toxic multinodular goiter. After the operation, the patient was transiently hypothyroid and had no VT without medication. A review of the literature revealed no previously documented cases of VT with toxic multinodular goiter.

Aluminum-controlled reactivity and diastereoselectivity toward radical reactions of optically active aldimines with metallic samarium.

The intermolecular pinacol-type coupling reaction and allylation reaction of optically active imines bearing a beta-hydroxy group were performed stereoselectively with metallic samarium after treatment of the imines with trimethylaluminum.

Pathology of chronic vitamin E deficiency in fatal familial intrahepatic cholestasis (Byler disease).

A case of fatal familial intrahepatic cholestasis (Byler disease) developed a neuromuscular syndrome similar to that in experimental vitamin E deficiency and abetalipoproteinemia, and died of hepatic and cardiac failure. Serum vitamin E level was extremely low. Autopsy revealed intrahepatic cholestatic cirrhosis without obliterative lesions in the bile duct system and marked splenomegaly with splenoma-like nodules. The other pathological lesions were considered to be due to chronic vitamin E deficiency as follows:1. Mitochondrial changes especially of the hepatocyte and cardiac muscle. 2. Cardiomyopathy. 3. Myopathy. 4. Vasculopathy. 5. Systemic lipofuscinosis. 6. Lesions of the reproductive and endocrine organs. 7. Kyphoscoliosis and pes cavus. 8. Systemic neuroaxonal dystrophy with peripheral neuropathy.

The DSL domain in mutant JAG1 ligand is essential for the severity of the liver defect in Alagille syndrome.

Alagille syndrome (AGS) is a congenital multi-system anomaly mainly characterized by paucity of intrahepatic bile ducts caused by haploinsufficiency of the Jagged 1 gene (JAG1). To explore the relationship between genotype and phenotype, we analyzed the JAG1 gene in 25 Japanese AGS families at the genomic DNA level and identified 15 point mutations and one large deletion. Analysis of the genotype and phenotype strongly indicated that the Delta/Serrate/Lag-2 (DSL) domain in JAG1 protein played an essential role in determining the severity of the liver disorder. In four sporadic cases, missing an entire DSL domain in mutant JAG1 resulted in progressive liver failure and all 4 patients needed a liver transplant at a very young age. This correlation was further confirmed by statistical analysis (chi2=9.143, p<0.001). Our finding demonstrated that the DSL domain in JAG1 appears to be essential for normal liver development and function.

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.