A case of mucolipidosis II: biochemical, nutritional, and immunological studies

A case of mucolipidosis II was studied biochemically, nutritionally and immunologically. A possible functional deficiency of T cells was observed, but discrepancy between B cells and immunoglobulin content was not reasonably explained at this moment. There was no basic nutritional problem in this case and it is more likely that his growth retardation was due to frequent episodes of severe respiratory infection because he received adequate calorie intake with low normal basal metabolic rate. Results of enzymatic assays were also presented.     

Dopa-responsive dystonia: clinical, genetic, and biochemical studies]

Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of levodopa. There are at least three causative genes for DRD: (1) the GCH1 gene on chromosome 14q22.1-q22.2, which encodes GTP cyclohydrolase I (GTPCH), the first enzyme in the biosynthetic pathway for tetrahydrobiopterin (BH4; the essential cofactor for tyrosine hydroxylase [THI]), (2) the TH gene on 11 p15.5, coding for the enzyme TH that catalyzes the rate-limiting step in the catecholamine biosynthesis, and (3) an as yet undefined gene on 14q13 (DYT14). In reports on DRD, in which conventional genomic DNA sequencing of GCH1 was conducted in a relatively large number of pedigrees, mutations in the coding region (including the splice sites) of this gene were found in approximately 60% (range: 49-79%) of DRD families. In our series, after conducting additional GCH1 testing (Southern blotting, cDNA sequencing, etc.) and TH analysis, 86% of families with DRD or dystonia with motor delay (an intermediate phenotype between GTPCH-deficient DRD [mild] and GTPCH-deficient hyperphenylalaninemia [severe]) had identifiable GCH1 or (rarely) TH mutations. Up to the present, only one pedigree with autosomal dominant DRD linked to the DYT14 locus has been reported. Neuropathological findings (no Lewy bodies and a normal population of cells with reduced melanin in the substantia nigra) in DRD patients with GTPCH dysfunction were similar to those in a patient with DYT14 dystonia. There have been no reports of autopsied patients with TH-deficient DRD. Neurochemical data suggest that striatal dopamine reduction in GTPCH-deficient DRD is caused not only by decreased TH activity resulting from a low cofactor (BH4) level but also by actual loss of TH protein without nerve terminal loss. This TH protein reduction in the striatum, especially in the putamen, may be due to a diminished regulatory effect of BH4 on stability (rather than expression) of TH molecules or to a dysfunction of TH protein transport from the substantia nigra to the striatum. The extent of striatal TH protein loss may be critical in determining DRD symptomatology and could contribute to gender-related incomplete penetrance of GCH1 mutations in GTPCH-deficient DRD families. Notwithstanding the discovery of the three causative loci for DRD, a therapeutic trial with low doses of levodopa is still the most practical approach to the diagnosis of this treatable disorder. The trial should be considered in all children with dystonic and/or parkinsonian symptoms or with unexplained gait disorders. Analyses of total biopterin and neopterin as well as neurotransmitter metabolites in CSF appear to be useful for the diagnosis of GTPCH-deficient DRD (the major form of DRD) and of TH-deficient DRD (the mild form of TH deficiency). Findings of the precise mechanism of striatal TH protein loss in GTPCH-deficient DRD, the actual status of dopaminergic systems in TH-deficient DRD, and the novel causative gene on the DYT14 locus will better define the pathogenesis of DRD.     

Hereditary motor neuropathy, distal type: electrophysiological and pathological studies of a case

A case of HMN, distal type transmitted as autosomal dominant is described. Clinical findings appear to be consistent with a peroneal muscular atrophy, indistinguishable from HMSN types I and II. The electrophysiological data reveal a pathological involvement of the anterior horns, whereas sensory and motor conduction are normal. A muscle biopsy showed neurogenic atrophy, while the morphology of the sural nerve was normal.

---

Sommario Viene presentato un caso di HMN distal type trasmesso in modo autosomico dominante. La clinica appare essere quella di una atrofia muscolare peroneale indistinguibile da quella tipo HMSN I e II. I dati elettrofisiologici indicano la presenza di sofferenza delle corna anteriori mentre normale risulta essere la conduzione sia sensitiva che motoria. La biopsia muscolare mostra atrofia neurogena mentre normale appare la morfologia del nervo surale. Si discute il caso alla luce della letteratura.

     

Clinical and pathological studies on nemaline myopathy in adulthood]

We examined 22 biopsied muscles from adult patients who had the histopathological characteristics of nemaline myopathy. In the first group, 13 patients had muscle weakness and/or skeletal abnormalities, such as high-arched palate, pes cavus and scoliosis which are often accompanied with the congenital nemaline myopathy. Their appropriate diagnosis had never been made until muscle biopsy was done, because of benign clinical course. In the second group, the symptoms of nine patients became manifest in adulthood and failed to show typical skeletal abnormalities. However, six muscle biopsies showed the histopathologic characteristics of congenital nemaline myopathy; abnormal fiber type distribution including type 1 fiber predominancy, type 1 fiber atrophy and type 2B fiber deficiency. Three patients remained in good health until adulthood when they developed muscle weakness with pathologic findings of nemaline myopathy. Accordingly, nemaline myopathy in adulthood can be categorized into three forms; the first two forms have clinical and pathologic evidence of the congenital benign form, whereas the symptoms are too mild to be noticed. The third form is not a hereditary disorder which may result from autoimmune pathophysiology.     

Multiple cerebral embolism in acute alcoholic intoxication. A pathological case]

A 37 year-old man sustained 2 ischemic strokes during acute alcohol intoxication. One month after the onset of strokes, a spontaneous atrial flutter occurred. Autopsy revealed an embolic rostral occlusion of the basilar artery. Cardiac verification did not show myocardiopathy or coronary disease. The relations between acute alcoholic intoxication and paroxystic cardiac rhythm disorders are discussed.     

A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies

Summary Clinical and biochemical studies are reported on a 32-year-old man with GM₁ gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM₁ ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM₁ ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM₁ ganglioside -galactosidase activity was only 10% of normal. These findings suggest that impaired GM₁ ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM₁ gangliosidosis.     

A case of Moebius syndrome--electrophysiological studies of facial nerve and brainstem]

A five-year old boy was the product of a 40 week pregnancy by vertex presentation complicated only by threatened abortion at approximately 8 weeks gestation. Apgar score was 5 after one minute. At birth he was noted to have a generalized hypotonia associated with facial diplegia, small mandible, weak suck and swallow reflexes. Admission examination revealed small mandible, mask-like facial expression and mild mental retardation. Cranial nerve examination showed bilateral blepharoptosis and facial nerve palsies. Pupil reflexes were normal, but corneal reflexes were impaired bilaterally. Diplopia due to the left abducens nerve palsy was suggested. There was no atrophy of the tongue. Motor tone, strength, and deep tendon reflexes were normal. A normal 46 XY karyotype was present. The other clinical and laboratory findings were normal. MRI of the brain was unremarkable. The characteristics of electrophysiological studies were summarized as follows: 1) Auditory brainstem evoked responses demonstrated waveforms IV-V were abnormal because their amplitudes were less than 30% of wave I bilaterally. 2) Somatosensory evoked potentials documented by central conduction times from cervical region to sensory cortex were prolonged on both sides. 3) Facial nerve conduction velocity was calculated by evoked EMGs of the mentalis muscle electrically stimulated at two distal points over the marginal mandibular branch. MCV of the left side was reduced (34.2 m/sec). 4) The amplitude of the facial muscle potentials evoked by facial nerve stimulation was reduced on both sides. 5) Blink reflex responses documented by the latency difference of R1 responses between the two sides were prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of acid maltase deficiency (juvenile type)--immunohistochemical and biochemical study]

A 22-year-old housewife was referred to us for review of progressive proximal muscle weakness which started at 15 years of age. A biopsy of left rectus femoris muscle showed acid phosphatase positive vacuoles partly filled with PAS-positive material. Acid maltase activity of the cultured fibroblasts was pathologically low at 0.4 nmol/mg protein considering 161.0 +/- 32.4 nmol/mg protein as a normal range. A diagnosis was made of acid maltase deficiency (juvenile type). Western blot using anti-acid maltase polyclonal antibody revealed 115 and 70 kDa bands in control muscles, where as only the 115 kDa band, a presumable precursor of the enzyme, was visualized in the patient. By immunohistochemistry using the same antibody the epitope was localized to the acid phosphatase positive vacuoles and immunoelectron microscopy demonstrated the acid maltase immunoreactivity within lysosomes. We concluded that the protein precursor unable to proceed into mature enzyme can access to lysosomes from endoplasmic reticulum through Golgi complex in the present case.     

A case of multiple sclerosis with pathological laughing caused by pontine base lesions]

We report a case of multiple sclerosis (MS) with pathological laughing for which lesions in pontine bases are considered to be responsible. A 30-year-old man was diagnosed as having MS based on left hemiparesis, and pathological laughing, and MRI findings showing a plaque in the right pontine base as well as several plaques in the bilateral periventricular deep white matter. After remission for 6 years, his pathological laughing exacerbated in association with development of right hemiparesis. A new lesion in the left pontine base was demonstrated by MRI studies in addition to a few supratentorial lesions. Steroid pulse therapy was effective for both pathological laughing and right hemiparesis. We speculate that the anatomical lesion responsible for the pathological laughing is located in the pontine base.     

A case of neuronal ceroid-lipofuscinosis (Jansky-Bielshowsky type): morphological, biochemical and electrophysiological studies (author's transl)

We reported a case of late infantile neuronal ceroid-lipofuscinosis. The patient was an 8-year-old boy presenting with marked psychomotor deterioration, progressive visual failure due to retinal degeneration and optic atrophy, startle reaction to auditory stimuli, frequent myoclonus and generalized convulsions. The routine laboratory examinations were all normal. EEG was markedly abnormal because of poorly organized background activity and frequent paroxysmal spike-and-wave complexes. CT scan showed evidence of severe atrophy of the cerebrum, cerebellum and brainstem. Electron microscopic examination of the biopsied rectum revealed fingerprint profiles in the neurons and pericytes beneath the muscularis mucosa. Cultured skin fibroblasts also contained electron dense inclusions, some of which showed fingerprint profiles. Urinary glycopeptides were normal. Lyscsomal enzyme activities in leukocytes and cultured fibroblasts were normal. Neurophysiological studies revealed giant cortical potentials evoked by the auditory as well as somatosensory stimulation. Simultaneous recording of the somatosensory evoked EEG and EMG potentials disclosed that the myoclonus in this patient was stimulus-sensitive and compatible with the cortical reflex myoclonus. With regard to hypothetical pathogenesis of this disease, we studied lipoperoxide in the blood before and after anti-oxidant therapy. We also measured vitamin A and carotene, since these substrates are related to retinoic acid. Although vitamin A and carotene were normal, lipoperoxide was slightly elevated. However, it was not influenced by the treatment with anti-oxidant. Significance of elevated lipoperoxide to the pathogenesis of this diseases has not solved.     

An autopsied case of dentato-rubro-pallido-luysian atrophy with atypical pathological lesions]

In this paper, atypical pathological findings in a genetic diagnosed case of dentato-rubro-pallido-luysian atrophy (DRPLA) with mild degeneration in the common lesions of the disease is reported. The patient was 59-year-old woman with 31-year history of involuntary movement, ataxia and psychiatric disorders. Her CAG repeat number of DRPLA gene was 68/14. Besides the spongy degeneration in the third and fourth layers of the occipital cortex, severe degenerations were observed in the cerebellar cortex and white matter, inferior olive, posterior funicular nuclei of the medulla oblongata, posterior and lateral funicles of the spinal cord, and Clarke's nucleus. A wide spread distribution of the intracellular polyglutamine aggregation was also showed including both common and uncommon lesions. Genetic diagnosis disclosed a DRPLA case with lesions different from the conventional cases.