ABSTRACT
We report a new neurocutaneous syndrome of apparent autosomal recessive inheritance consisting of early-childhood-onset palmoplantar keratoderma followed in adulthood by progressive tetrapyramidal syndrome and cognitive impairment. Of the four affected siblings, two were available for evaluation. Investigation disclosed cerebral white-matter involvement on MRI and arylsulfatase A pseudodeficiency carrier state, which was also identified in clinically unaffected family members. Since skin biopsies showed dermal connective tissue abnormalities, we studied collagens I, III, and VI biosynthesis. Northern blotting of RNA extracted from cultured skin fibroblasts revealed an increased steady-state messenger RNA (mRNA) level of alpha 1(VI) collagen, whereas no differences were detected for pro alpha 1(I), pro alpha 1(III), and tropoelastin mRNAs. The skin content of collagen and total protein was higher in the patients than in controls. We suggest that an extracellular matrix abnormality may be involved in the pathogenesis of this disorder.
Subject(s)
Collagen/biosynthesis , Demyelinating Diseases/genetics , Keratoderma, Palmoplantar/genetics , Skin/metabolism , Adult , Biopsy , Brain/pathology , Cerebroside-Sulfatase/deficiency , Collagen/analysis , DNA Probes , Demyelinating Diseases/metabolism , Demyelinating Diseases/pathology , Female , Humans , Hydroxyproline/analysis , Keratoderma, Palmoplantar/metabolism , Keratoderma, Palmoplantar/pathology , Magnetic Resonance Imaging , Male , Pedigree , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Skin/pathology , SyndromeABSTRACT
We report the familial occurrence and apparent autosomal dominant inheritance of Sneddon's syndrome with variable clinical expression. The proband, a 40-year-old woman, presented with livedo reticularis and progressive neurological deterioration following a stroke. The diagnosis was confirmed by cerebral angiogram and skin biopsy, both showing the characteristic findings. Two of the patient's sisters were reported to have been similarly affected in the past. Her mother, two additional siblings and five of her seven children exhibited various vasospastic skin phenomena. Familial aggregation of this disorder may be common and a genetic basis may be involved in its pathogenesis.
Subject(s)
Cerebrovascular Disorders/genetics , Skin Diseases, Vascular/genetics , Adolescent , Adult , Brain/pathology , Brain Ischemia/diagnosis , Cerebral Infarction/diagnosis , Cerebrovascular Disorders/diagnosis , Female , Genes, Dominant , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pedigree , Skin/pathology , Skin Diseases, Vascular/diagnosis , SyndromeABSTRACT
We describe 2 unrelated patients with adult polyglucosan body disease (APBD) diagnosed by sural nerve biopsy. Both patients were offspring of consanguineous marriages. They presented clinically with late onset pyramidal tetraparesis, micturition difficulties, peripheral neuropathy, and mild cognitive impairment. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities in both. In search of a possible metabolic defect, we evaluated glycogen metabolism in these patients and their clinically unaffected children. Branching enzyme activity in the patients' polymorphonuclear leukocytes was about 15% of control values, whereas their children displayed values of 50 to 60%, suggesting a possible autosomal recessive mode of transmission. This is the first report of an inherited metabolic defect in patients with adult polyglucosan body disease. We suggest that branching enzyme dysfunction may be implicated in the pathogenesis of some patients with adult polyglucosan body disease.
