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Amylo-1,6-glucosidase deficiency (glycogen storage disease type III) is associated with hypoglycaemia, hepatomegaly, raised transaminases and in most cases skeletal myopathy and cardiomyopathy. The disorder has not been considered to cause dysmorphism. We report consistent facial features in seven patients with GSD type III consisting of midface hypoplasia with a depressed nasal bridge and a broad upturned nasal tip, indistinct philtral pillars, and bow-shaped lips with a thin vermillon border. Younger patients had in addition deepset eyes. Several children had clinical problems such as persistent otitis media or recurrent sinusitis. The underlying aetiology of these features is unknown but the similarity in all our patient suggests that there is a facial phenotype for this disorder.

An inborn error of metabolism, homocystinuria due to cystathionine beta-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess the effectiveness of long-term homocysteine-lowering treatment in reducing vascular risk in 158 patients. Vascular outcomes were analyzed and effectiveness of treatment in reducing vascular risk was evaluated by comparison of actual to predicted number of vascular events, with the use of historical controls from a landmark study of 629 untreated patients with cystathionine beta-synthase deficiency. The 158 patients had a mean (range) age of 29.4 (4.5 to 70) years; 57 (36%) were more than 30 years old, and 10 (6%) were older than 50 years. There were 2822 patient-years of treatment, with an average of 17.9 years per patient. Plasma homocysteine levels were markedly reduced from pretreatment levels but usually remained moderately elevated. There were 17 vascular events in 12 patients at a mean (range) age of 42.5 (18 to 67) years: pulmonary embolism (n=3), myocardial infarction (n=2), deep venous thrombosis (n=5), cerebrovascular accident (n=3), transient ischemic attack (n=1), sagittal sinus thrombosis (n=1), and abdominal aortic aneurysm (n=2). Without treatment, 112 vascular events would have been expected, for a relative risk of 0.09 (95% CI 0.036 to 0.228; P<0.0001). Treatment regimens designed to lower plasma homocysteine significantly reduce cardiovascular risk in cystathionine beta-synthase deficiency despite imperfect biochemical control. These findings may be relevant to the significance of mild hyperhomocysteinemia that is commonly found in patients with vascular disease.

It has been reported that astrocytes in the white matter of patients with multiple sclerosis (MS) lack beta2-adrenergic receptors. This abnormality might explain why astrocytes in active MS plaques aberrantly express major histocompatibility (MHC) class II molecules, which play an important role in the immunological cascade leading to myelin destruction. Canine distemper (CD) virus primarily infects astrocytes and causes a demyelinating disease in dogs that closely resembles MS. In control dogs, including three dogs with another inflammatory disease, beta2-adrenergic receptor immunoreactivity was observed on both neurons and astrocytes. In dogs with CD encephalitis, beta2-adrenergic receptors were present on neurons, but were absent on astrocytes in acute lesions, demyelinated lesions, and normal-appearing white matter. Similar to MS, several astrocytes in demyelinated lesions expressed MHC class II. These findings suggest that MS and the demyelinating stages of CD encephalitis have a common pathogenetic factor, and that the loss of astrocytic beta2-adrenergic receptors in MS might be induced by a viral infection of astrocytes.