Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor

Two children with glycogen storage disease type 1B developed chronic inflammatory bowel disease. The first, a 7-year-old boy, had ileitis and later developed perianal disease. The second developed colitis by the age of 9 years; in both the features were consistent with Crohn disease. The children had neutropenia and neutrophil mobility defects characteristic of GSD-1B. It is suggested that these neutrophil abnormalities are important in the pathogenesis of the bowel inflammation.

Chronic inflammatory bowel disease in glycogen storage disease type 1B.

Two unrelated children presented with similar clinical features (facial dysmorphism and multiple joint dislocations) suggesting the diagnosis of Larsen syndrome. Both carried an inherited unbalanced translocation resulting in partial trisomy 1q and partial monosomy 6p. Analysis of skin collagen from one of the probands disclosed a decreased alpha 1/alpha 2 chain ratio of collagen type I, increased thermal stability and increased hydroxylation of proline and lysine. The present findings suggest that, as a result of the chromosome rearrangements, both patients have a mutation on a gene involved in collagen production, located either on chromosome 1q or, more probably, on 6p. It is furthermore suggested that other cases of Larsen syndrome are the result of a similar mutation.

Two unrelated children with partial trisomy 1q and monosomy 6p, presenting with the phenotype of the Larsen syndrome.

We report a case of ring chromosome 6 presenting with growth and mental retardation, cerebral dysgenesis, eye malformations, mixed hearing loss, and abnormal physical features. Fluorescent in situ hybridization (FISH) and microsatellite genotyping demonstrated segmental deletions of less than 6 Mb on 6p and 1-2 Mb on 6q. The primary karyotype is designated as 46,XY,r(6)(p25q27).ish r(6)(p25.1q27)(D6S344-, FOXC1-, D6S1574+, D6S281-, D6S297+). Secondary structural and numerical variants of the ring 6 were observed in 16% of the cells analyzed. Intragenic genotyping revealed deletion of the paternal FOXC1 gene, haploinsufficiency of which has been reported to cause eye anterior chamber developmental defects. Accordingly, we propose that our patient's ophthalmologic abnormalities result from haploinsufficiency of the transcription factor FOXC1. We present clinical and cytogenetic summaries on 23 reported cases of ring 6 and categorize them into mild, moderate, and severely affected groups. Further phenotype comparisons between cases with ring 6 and cases with only 6p or 6q terminal deletions suggest that genes important for hearing, vision, and central nervous system development remain to be identified in chromosome 6 terminal regions. Molecular definition of the fusion points and tissue mosaicism studies are necessary to better understand the genotype-phenotype correlation of ring 6. We recommend ophthalmology, audiology, cardiology, and central nervous system examinations be part of the routine evaluation for children with a ring chromosome 6.

FOXC1 gene deletion is associated with eye anomalies in ring chromosome 6.

Hemorrhagic shock and encephalopathy: Clinical, pathologic, and biochemical features

Sir: The diagnosis of the fetal alcohol syndrome is based on well-known, variable clinical signs and a history of excessive alcohol consumption during pregnancy. A 15-month-old girl displayed the phenotype of fetal alcohol syndrome with short stature, preand postnatal dystrophy, microcephaly, psychomotor retardation and abnormal facial features (Fig. 1). In addition, the child had a small ventricular septal defect and a haemangioma over the left eyebrow. The mother reported having consumed one bottle of wine at the time the unwanted pregnancy was noted but denied any alcohol intake thereafter. Since the mother seemed to be reliable and as there were no signs of prenatal infection or other causes of the retardation-multiple anomaly syndrome, a chromosomal analysis was performed. Chromosomal analysis was carried out on peripheral lymphocytes and cul-

Erroneous diagnosis of fetal alcohol syndrome in a patient with ring chromosome 6.

Upon isoelectric focusing, alpha 1-antitrypsin shows a characteristic major band pattern caused by glycoprotein isoforms with different oligosaccharide side chains. In ten apparently healthy individuals with the Pi type MM the ratio of isoforms I, II, and III was 5.2:3.9:1.0. In six patients with glycogen storage disease Ib the ratio of isoforms in the Pi type MM was 3.6:5.5:1.9 suggesting a shift from the biantennary to triantennary oligosaccharide side chains. This shift may result from the limited availability of glucose or glucose derivatives for the synthesis of N-glycosidic glycoproteins.

Glycogen storage disease Ib: modification of alpha 1-antitrypsin glycoprotein microheterogeneity.

Microheterogeneity of the glycoprotein α1 has been investigated sequentially by high resolution isoelectric focusing in a child with the proteinase inhibitor MS phenotype after near-drowning A band-splitting with additional cathodal fractions exhibited migration from the most cathodic to the anodic positions of the glycoprotein isoforms in the course of postresuscitation disease. The pattern may reflect the time- and stage-dependent hypoxic and post-hypoxic effects on hepatocellular metabolic zonation.

K. Heyne

Papers

Erroneous diagnosis of fetal alcohol syndrome in a patient with ring chromosome 6.

Glycogen storage disease Ib: modification of alpha 1-antitrypsin glycoprotein microheterogeneity.

Variation of 789-1789-1789-1glycoprotein microheterogeneity in hepatic postresuscitation disease