Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes.

Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic control.

While the presence of hyperlipidaemia in glycogen storage disease (GSD) type Ia and Ib is generally accepted, few investigators have adequately assessed lipid profiles of GSD III in children, in whom the presence of hyperlipidaemia may be most prominent. We analysed the lipid profiles in 44 GSD III patients from 6 months to 30 years of age. Hypertriglyceridaemia and hypercholesterolaemia were common in children younger than 3 years of age. Hypertriglyceridaemia correlated negatively with age, and may reflect increased severity of hypoglycaemia in this younger population. The presence of hyperlipidaemia during childhood in these patients identifies another GSD population that could be at risk for early cardiovascular disease (CVD). Consequently, the outcome of clinical trials investigating the vascular effect of hyperlipidaemia in GSD applies to types other than GSD I.

Adalimumab for the treatment of Crohn-like colitis and enteritis in glycogen storage disease type Ib.

Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil dysfunction, and an inflammatory bowel disease that mimics a Crohn phenotype. Gastrointestinal inflammation in GSD Ib has been successfully treated with 5-aminosalicylic acid and granulocyte colony-stimulating factor (G-CSF). However, therapeutic options for patients not responding to traditional therapies have been limited owing to untoward effects of glucocorticoids and immunomodulators in this metabolic disorder. Adalimumab is a monoclonal antibody targeting tumour necrosis factor-α that has shown promise for the treatment of patients with Crohn disease. Due to the limited options for treating GSD-associated inflammatory bowel disease, use of adalimumab was attempted in a case unresponsive to aminosalicylate, G-CSF, and antibiotic therapy. Significant clinical and histological improvement was observed in our patient, and the medication was well tolerated.

Hepatocellular carcinoma in glycogen storage disease type Ia: a case series.

We present a series of 8 patients (6 males, 2 females) with hepatocellular carcinoma (HCC) and glycogen storage disease type Ia (GSD Ia). In this group, the age at which treatment was initiated ranged from birth to 39 years (mean 9.9 years). All patients but one were noncompliant with treatment. Hepatic masses were first detected at an age range of 13-45 years (mean 28.1 years). Age at diagnosis of HCC ranged from 19 to 49 years (mean 36.9 years). Duration between the diagnosis of liver adenomas and the diagnosis of HCC ranged from 0 to 28 years (mean 8.8 years, SD = 11.5). Two patients had positive hepatitis serologies (one hepatitis B, one hepatitis C). Alpha-fetoprotein (AFP) was normal in 6 of the 8 patients. Carcinoembryonic antigen (CEA) was normal in the 5 patients in which it was measured. Current guidelines recommend abdominal ultrasonography with AFP and CEA levels every 3 months once patients develop hepatic lesions. Abdominal CT or MRI is advised when the lesions are large or poorly defined or are growing larger. We question the reliability of AFP and CEA as markers for HCC in GSD Ia. Aggressive interventional management of masses with rapid growth or poorly defined margins may be necessary to prevent the development of HCC in this patient population.

Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy.

The glycogen storage diseases are caused by inherited deficiencies of enzymes that regulate the synthesis or degradation of glycogen. In the past decade, considerable progress has been made in identifying the precise genetic abnormalities that cause the specific impairments of enzyme function. Likewise, improved understanding of the pathophysiologic derangements resulting from individual enzyme defects has led to the development of effective nutritional therapies for each of these disorders. Meticulous adherence to dietary therapy prevents hypoglycemia, ameliorates the biochemical abnormalities, decreases the size of the liver, and results in normal or nearly normal physical growth and development. Nevertheless, serious long-term complications, including nephropathy that can cause renal failure and hepatic adenomata that can become malignant, are a major concern in GSD-I. In GSD-III, the risk for hypoglycemia diminishes with age, and the liver decreases in size during puberty. Cirrhosis develops in some adult patients, and progressive myopathy and cardiomyopathy occur in patients with absent GDE activity in muscle. It remains unclear whether these complications of glycogen storage disease can be prevented by dietary therapy. Glycogen storage diseases caused by lack of phosphorylase activity are milder disorders with a good prognosis. The liver decreases in size, and biochemical abnormalities disappear by puberty.

Osteoporosis after spinal cord injury.

Dual-photon absorptiometry characterized bone loss in males aged less than 40 years after complete traumatic paraplegic and quadriplegic spinal cord injury. Total bone mass of various regions and bone mineral density (BMD) of the knee were measured in 55 subjects. Three different populations were partitioned into four groups: 10 controls (healthy, age matched); 25 acutely injured (114 days after injury), with 12 reexamined 16 months after injury; and 20 chronic (greater than 5 years after injury). Significant differences (p less than 0.0001) in bone mass mineral between groups at the arms, pelvis, legs, distal femur, and proximal tibia were found, with no differences for the head or trunk. Post hoc analyses indicated no differences between the acutely injured at 16 months and the chronically injured. Paraplegic and quadriplegic subjects were significantly different only at the arms and trunk, but were highly similar at the pelvis and below. In the acutely injured, a slight but statistically insignificant rebound was noted above the pelvis. Regression techniques demonstrated early, rapid, linear (p less than 0.0001) decline of bone below the pelvis. Bone mineral loss occurs throughout the entire skeleton, except the skull. Most bone loss occurs rapidly and below the pelvis. Homeostasis is reached by 16 months at two thirds of original bone mass, near fracture threshold.

Metabolism of Radiolabeled beta-Guaiacyl Ether-Linked Lignin Dimeric Compounds by Phanerochaete chrysosporium.

Phanerochaete chrysosporium metabolized the radiolabeled lignin model compounds [gamma-C]guaiacylglycerol-beta-guaiacyl ether and [4-methoxy-C]veratrylglycerol-beta-guaiacyl ether (VI) to CO(2) in stationary and in shaking cultures. CO(2) evolution was greater in stationary culture. CO(2) evolution from [gamma-C]guaiacyl-glycerol-beta-guaiacyl ether and [4-methoxy-C]veratrylglycerol-beta-guaiacyl ether in stationary cultures was two- to threefold greater when 100% O(2) rather than air (21% O(2)) was the gas phase above the cultures. CO(2) evolution from the metabolism of the substrates occurred only as the culture entered the stationary phase of growth. The presence of substrate levels of nitrogen in the medium suppressed CO(2) evolution from both substrates in stationary cultures. [C]veratryl alcohol and 4-ethoxy-3-methoxybenzyl alcohol were formed as products of the metabolism of VI and 4-ethoxy-3-methoxyphenylglycerol-beta-guaiacyl ether, respectively.