Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation.

We report findings in a Japanese boy with severe skin rash attributable to biotin deficiency. The patient had an intracranial malformation and developed biotin deficiency due to tube feeding with a single formula for over one year. Results of urinary organic acid analysis were consistent with multiple carboxylase deficiency, and low biotinidase activity was also observed. After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase.

[Mitochondrial DNA T to G mutation 8993 in Leigh encephalopathy and organic aciduria].

We report a 10-month-old female infant with Leigh encephalopathy caused by a T to G mutation at nucleotide 8993 of mitochondrial DNA. Initial manifestations were diarrhea and pyrexia, followed by disturbance of consciousness. Blood chemistry showed lactic acidosis, and cranial T2 weighted magnetic resonance imaging demonstrated symmetric high-intensity areas in the basal ganglia, consistent with Leigh encephalopathy. Analysis of urinary organic acids revealed a increase of alpha-ketoglutamate. Derivatives of branched chain amino acids, which accumulate in maple syrup disease, were also increased. Lipoamide dehydrogenase (E3) deficiency was initially suspected; however, normal activity of pyruvate dehydrogenase complex excluded the diagnosis. The organic aciduria disappeared after two weeks. The CNS lesions in our case were observed more prominently in the floor of the bilateral frontal lobes than in the globus pallidus and putamen. In this case, mitochondrial DNA mutation may have caused organic aciduria and the atypical imaging findings.

Application of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry for analysis of sphingolipids in tissues from sphingolipidosis patients.

Sphingolipidosis is due to defects in enzymes involved in hydrolysis of sphingolipids. We analyzed sphingolipids in tissues from patients with sphingolipidosis, including Farber disease (FD, acid ceramidase deficiency), Gaucher disease (GD), Niemann-Pick disease type C (NPDC), and GM1-gangliosidosis (GM1G), using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). Crude lipids were extracted from about 100 mg wet weight of autopsied tissues, including liver, spleen, cerebrum or cerebellum. After mild alkaline treatment, a sphingolipid fraction was prepared from the crude lipids and analyzed by DE MALDI-TOF-MS. The results were as follows: (a) In FD liver both the ceramide/sphingomyelin and ceramide/monohexosylceramide ratios were significantly high; (b) in both liver and spleen from a GD patient, the glucosylceramide/sphingomyelin ratio was raised; (c) in liver from a NPDC patient, the monohexosylceramide/sphingomyelin ratio was markedly low, suggesting an increase of sphingomyelin; and (d) in all tissues examined in the GM1G patient, GM1-gangliosides or asialo-GM1-gangliosides, that are undetectable in a normal control, were increased. In conclusion, sphingolipids in human tissues could be directly determined by DE MALDI-TOF-MS, with only a small amount of specimens. This method will be useful for the diagnosis and biochemical evaluation of sphingolipidosis patients.

Tissue accumulation of sulfatide and GM3 ganglioside in a patient with variant Farber disease.

We analyzed the lipids in the tissues of a patient with an atypical form of Farber disease who developed several clinical symptoms not seen in patients with typical Farber disease (acid ceramidase deficiency). Lipids were extracted from formalin-fixed brain, liver and kidney and purified by ion exchange and silica gel column chromatographies and further by high-performance liquid chromatography on a silica gel column. We performed structural and quantitative analyses of three lipids named lipids X, Y and Z. Lipid X accumulated in the liver but not in the brain. Accumulation of lipids Y and Z was observed in liver and kidney. The content of lipid Y in the patients liver was more than ten times that in a control. The structures of lipids X, Y and Z were confirmed by means of 1H-nuclear magnetic resonance spectroscopy, fast atom bombardment mass spectrometry, infrared absorption spectroscopy, and component analysis involving gas liquid chromatography and gas chromatography-mass spectrometry. The structures of lipids X, Y and Z were identified as those of ceramide, sulfatide and GM3 ganglioside, respectively. These results suggest two possibilities. One is that the accumulation of glycolipids such as sulfatide and GM3 ganglioside is a secondary event produced by the accumulation of ceramide due to ceramidase deficiency. The other is that the accumulation of glycolipids other than ceramide is due to a deficiency of sphingolipid activator proteins which may affect the degradation of sulfatide and GM3 ganglioside as well as ceramide.

The effects of rice bran broth bathing in patients with atopic dermatitis.

We determined the effects of rice bran broth bathing therapy in 17 outpatients with atopic dermatitis. The rice bran broth used in this study was made in our hospital and distributed to the patients who dissolved it in the bathtub as a medicinal bath. In the case of one patient, redness and itching of the skin increased just after bathing. The patient subsequently discontinued therapy. We followed the other 16 patients who performed rice bran broth bathing for 2-5 months and examined their skin symptoms once a month. The efficacy of this therapy in alleviating skin symptoms was excellent in four of the 16 evaluated patients, good in seven, slightly effective in four, and ineffective in one. None of the 16 patients experienced negative effects of treatment. Recurrence of initial symptoms was not detected in any patient during rice bran broth bathing. Rice bran broth bathing therapy appears to be safe and clinically useful.

A case of Farber disease.

We report a case of Farber disease (Farber lipogranulomatosis). The main features were a shrill voice, joint swelling, subcutaneous nodules and retarded psychomotor development. Cytological investigation revealed intracytoplasmic inclusion bodies characteristic of Farber disease. Lipid analysis of liver tissue indicated an accumulation of ceramide containing non-hydroxy fatty acids. It was found that the acid ceramidase activity in the liver was reduced to 31% of the control value. In this patient there was also persistent diarrhea, cholelithiasis, transient proteinuria and increased urinary total sialic acids. These features have not been noted in previously reported cases.

An autopsy case of Farber's lipogranulomatosis in a Japanese boy with gastrointestinal involvement.

A boy with Farber's lipogranulomatosis is reported. Excessive ceramide was revealed by thin-layer chromatography of the extracts from the liver. Acid ceramidase activity of the liver was 31.5% of control with exogenous substrate and 33.3% without exogenous substrate. The histological appearance showed granulomatous lesions, composed of spindle or oval-shaped storage cells and proliferation of the connective tissues, in the subcutaneous tissue of the lower lip, periarticular regions and the pericardium. Histochemically the storage cells were revealed to contain lipid and polysaccharide. The foreign body granuloma formed by the surgical suture in the liver was surrounded by a large number of foamy cells. In gastrointestinal mucosa widespread erosion, disappearance of glands and abundant collagen fibers were noted. On electron microscopy, the spindle or oval-shaped cells in the subcutis of the lip had intracytoplasmic inclusions containing granular or fibrillar materials and a smaller number of curvilinear structures, so called "Farber bodies". Our case was a typical clinical and histopathological presentation of Farber's lipogranulomatosis. However, ceramidase activity was higher than in previous descriptions, and severe gastrointestinal lesions and the appearance of a large number of foamy cells around the foreign body granuloma have not been described previously.