Juhani Rapola

Muscle-eye-brain disease (MEB)

Clinical features of a rare congenital myopathy, muscle-eye-brain (MEB) disease, are described in 19 patients. The pedigree data suggest an autosomal recessive inheritance. The patients presented with congenital hypotonia and muscle weakness. Serum CK was elevated, EMG was myopathic and muscle biopsy showed slight or moderate changes compatible with muscular dystrophy. Ophthalmological findings included severe visual failure and uncontrolled eye movements associated with severe myopia. The flash VEPs were exceptionally high, whereas non-corneal ERG was unrecordable. The EEG showed progressive abnormalities after the age of 6 months. Psychomotor development was slow during the first years of life, and mental retardation was severe. Most patients began to deteriorate around age 5 years. This change included spasticity and joint contractures. CT scans showed ventricular dilatations and abnormally low white matter density in several patients. Spasticity, high VEPs and ocular manifestations differentiate MEB from the Fukuyama type congenital muscular dystrophy.

Infantile type of so-called neuronal ceroid-lipofuscinosis

A clinical description is given of a uniform series of 15 patients with a progressive encephalopathy. The disease had its clinical onset at the age of 8 to 18 months with rapid psychomotor deterioration, ataxia, and muscular hypotonia. Microcephaly and myoclonic jerks were other prominent features; convulsions were few or did not occur at all. All patients were amaurotic by the age of 2 years and had optic atrophy and macular and retinal dystrophy without pigment aggregation. Early extinction of the electroretinogram and EEG records rapidly approaching isoelectricity were additional features. The clinical picture does not fit with any previously recognized type of amaurotic idiocy. However, the diagnostic morphological and biochemical findings (see Haltia et al. 1973) have a number of features in common with the group of so-called neuronal ceroid-lipofuscinoses. The relationship of the present condition and of some previously reported similar cases to the various forms of neuronal ceroid-lipofuscinosis is discussed.

Microscopic hematuria in schoolchildren: Epidemiology and clinicopathologic evaluation

An unselected population of 8,954 children, age 8 to 15 years, was screened for hematuria. Four urine specimens from each were examined; microscopic hematuria was found in one or more specimens in 4.1%, and in two or more specimens in 1.1% of the children. The prevalence was not age or sex dependent. Those with two or more positive samples were re-examined twice during a half-year period: 33 had hematuria of 6 or more RBC/0.9 mm3, or more than 100,000 RBC/hour, on both occasions; renal biopsy performed on 28 of them revealed two cases of IgA-IgG nephropathy, one of focal segmental sclerosis, one of extracapillary glomerulonephritis, and one of possible hereditary nephritis. In 12 patients the biopsy was entirely normal; the rest showed equivocal changes. Co-existing proteinuria and the degree of hematuria correlated well with the severity of the morphologic alterations. Pathologic findings in microscopic hematuria seem to be less frequent than in hematuria in general; in most such patients, renal biopsy is probably not indicated. In some children the low-grade hematuria may merely represent the upper end of physiologic variation.

Supplementary Creatine as a Treatment for Gyrate Atrophy of the Choroid and Retina

Gyrate atrophy of the choroid and retina is a disease characterized by progressive constriction of visual fields, a 10-fold to 20-fold elevation in plasma ornithine, and depressed activity of L-ornithine:2 oxoacid aminotransferase. Morphologically conspicuous but clinically unimportant atrophy of Type II muscle fibers progresses concomitantly with the eye disease. A pathogenic component of the disease may be deficient formation of creatine, caused by hyperornithinemia, which leads to a shortage of cellular phosphocreatine energy stores. To test the therapeutic value of replenishing the postulated deficiency of creatine, we supplemented the diet of seven patients with 1.5 g of creatine daily. During one year of this treatment the diameters of Type II muscle fibers increased from 34.1 +/- 7.1 to 49.9 +/- 7.0 micron (mean +/- S.D.) (P less than 0.001). There was no significant increase in the diameters of Type I fibers. The visual-field tests showed no further constriction during the therapy. Fundus photography revealed slow impairment at an age otherwise associated with rapid progression of the disease. These promising preliminary results need further evaluation with long-term follow-up studies.

Lysinuric protein intolerance

Lysinuric protein intolerance is an autosomal recessive disorder which first appears as failure to thrive, vomiting and diarrhea in the infant after weaning from mothers milk. Later it manifests as failure to grow, muscular weakness and osteopenia associated with aversion to animal protein. Some patients become mentally retarded and have periods of stupor. The disease is characterized by marked lysinuria, and hyperammonemia after protein intake. According to accumulating evidence, the basic defect is deficient transport of diamino acids in the intestine, liver and kidney tubuli. Effective treatment is provided by supplementing protein food with extra arginine.

Infantile type of so-called neuronal ceroid-lipofuscinosis ☆: Part 2. Morphological and biochemical studies

Morphological and biochemical data are given on brain biopsy or autopsy samples from 13 patients with a progressive encephalopathy, characterized clinically by the onset of rapid psychomotor deterioration at about 1 year of age, early amaurosis, and absence or relative paucity of convulsions. The main morphological feature was very severe neuronal destruction, accompanied by a massive occurrence of frequently binucleated phagocytes and unusually hypertrophic fibrillary astrocytes in the cerebral cortex. The remaining neurons and glial cells contained excessive amounts of autofluorescent granules with the staining properties of lipofuscin, and with strong acid phosphatase activity. The homogeneous granular ultrastructure of the storage material differed both from ordinary neuronal lipofuscin and from the storage material in most previous reports on so-called neuronal ceroid-lipofuscinosis. Biochemically the biopsy samples were characterized by a decrease in lipid-bound N-acetylneuraminic acid. Thus, the unusual but uniform clinical, morphological and biochemical findings in our series of 13 patients differ from the findings in previously recognized types of amaurotic idiocy. These 13 patients—and possibly some others collected from the literature—appear to constitute a clearly separable group; the relationship of this condition to various forms of neuronal ceroid-lipofuscinosis is discussed.

Immunohistochemical Spectrum of Rhabdomyosarcoma and Rhabdomyosarcoma-like Tumors: Expression of Cytokeratin and the 68-kD Neurofilament Protein

Twenty-five rhabdomyosarcomas (RMSs), including 12 alveolar and 13 embryonal types, were immunohistochemically studied for the presence of different classes of intermediate filament proteins and muscle actins (MAs). For the most part, formaldehyde-fixed and paraffin-embedded tissue was used in immunostaining. All RMSs showed desmin and MAs, usually in a major portion of tumor cells. The number of MA-positive cells was sometimes higher than that of desmin-positive cells. Vimentin was present in all tumors studied in frozen sections. Eight of 12 alveolar RMSs showed small number of cytokeratin-positive neoplastic cells. Cytokeratin-positive cells were present less commonly in embryonal RMS (3/13 cases). The 68-kD neurofilament protein was found in frozen sections of two embryonal RMSs. The cytokeratin and neurofilament immunostaining could be reproduced by immunofluorescence technique. In addition, we studied three childhood sarcomas, which showed abundant desmin and MA immunostaining but did not conform to the ultrastructural criteria of RMS. Scattered cytokeratin-positive cells were found in two of these tumors, and neurofilaments were found in the two cases for which frozen sections were available. The results show that typical RMS may demonstrate immunohistological pleomorphism with cytokeratin and neurofilament immunoreactivity suggesting the presence of multidirectional differentiation. In addition, there are tumors that by morphology look like RMS and have muscle cell markers but cannot be verified as RMS by electron microscopy; also, these tumors seem to show immunohistological pleomorphism. The presence of nonmyoid markers in RMS should be considered when making immunohistological diagnosis of soft tissue sarcomas.

Congenital Nephrotic Syndrome

Congentital nephrotic syndrome (CNS) is an uncommon disorder. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The problems associated with nephrotic syndrome in early infancy are divided into three parts: diagnosis, treatment and prenatal diagnosis. Accurate diagnosis is essential for the treatment, genetic counselling and prenatal diagnosis. The ultimate curative treatment of CNS is renal transplantation. The supportive treatment before the transplantation is of utmost importance in order to maintain a reasonable clinical condition and prepare the child for the dialysis and renal transplantation. Prenatal diagnosis is possible in some types of CNS by determination of the maternal serum and amniotic fluid alpha-fetoprotein (AFP). Increased AFP indicates fetal proteinuria, and thereby nephrotic syndrome before birth. In some cases with the onset of proteinuria after birth prenatal AFP measurement does not detect the disease.

Infantile Type of So‐called Neuronal Ceroid‐lipofuscinosis

A series of 46 patients with rapidly progressive encephalopathy is presented. The disease was characterised by psychomotor retardation, beginning between the ages of eight and 18 months and accompanied by ataxia, muscular hypotonia, visual degeneration, myoclonic jerks and microcephaly. Death occurred at a mean age of 6 1/2 years.

Isolated proteinuria: Analysis of a school-age population

Proteinuria was found in at least one of four specimens in 10.7% and in at least two of four specimens in 2.5% of 8,594 schoolchildren, ages 8 to 15 years. To determine the risk of renal disease in isolated proteinuria, the screening program was followed by a systematic clinical evaluation of the proteinuric children. After those with both proteinuria and hematuria were excluded, none of the remaining children was found to have an overt renal disease. Despite urinary protein concentrations in excess of 1,000 mg/dl and protein excretion rates of up to 1 gm in 24 hours, proteinuria proved to be transient or intermittent in every child when a large enough number of urine samples was tested. Children with the highest protein excretion rates (more than 6 mg/hour/m2 at night or more than 20 mg/hour/m2 during the day) and those with the most persistent patterns of proteinuria underwent renal function studies, intravenous pyelography, and renal biopsy. No significant abnormalities was found. Mild nonspecific changes were seen in 12 of 28 biopsies, with mesangial deposits in four. The results show that if hematuria and other signs have been excluded, a benign renal morphologic picture is almost invariably to be expected in intermittent proteinuria; renal biopsy, therefore, is not indicated.