Liver failure and x-linked immunodeficiency type 47.

Patients with defects in the ATP6AP1 gene have rarely been described. ATP6AP1-related disorders are a subtype of CDG, which result in enzyme deficiencies affecting multiple organ systems ranging from mild to life-threatening. Of the 13 patients described, all had hepatopathy, but this is the first case to be successfully transplanted. We describe two brothers who developed hyperbilirubinemia shortly after birth and progressed to liver failure, case 1 by 12 months of age, with successful transplant 2 years later, and case 2 by 4 months of age, who passed away while awaiting liver transplant. Both boys were found to have a new variant in the ATP6AP1 gene: c.932/p.Leu311Gln. Although the identified ATP6AP1 gene variant was classified as unknown significance at the time, both children's phenotypes fit with what has been described for ATP6AP1-related disorders. Therefore, this result appears to have been diagnostic for both boys. This rare type of CDG, X-linked immunodeficiency type 47 (OMIM #300972), particularly in patients who progress to liver failure requiring transplant, should be included on the differential of liver failure in infants and toddlers, and its gene should be added to the diagnostic workup for such cases.

Successful liver transplantation and long-term follow-up in a patient with MPI-CDG.

Hepatopathy is the most common feature in the Congenital Disorders of Glycosylation (CDG). More than 70 subtypes have been identified in this growing group of inborn errors. Most defects present as multisystem disease, whereas phosphomannose isomerase deficiency (MPI-CDG) presents with exclusive hepato-intestinal phenotype. MPI-CDG has been considered as one of the very few treatable disorders of glycosylation; several patients showed significant improvement of their life-threatening protein-losing enteropathy and coagulation disorder on oral mannose supplementation therapy. However, patients who have MPI-CDG develop progressive liver insufficiency during a later course of disease. A patient who had MPI-CDG developed progressive liver fibrosis, despite oral mannose supplementation and repeated fractionated heparin therapy. She showed mannose therapy-associated hemolytic jaundice. She developed severe dyspnea and exercise intolerance owing to pulmonary involvement, necessitating liver transplant. After transplantation her physical exercise tolerance, pulmonary functions, and metabolic parameters became fully restored. She is still doing well 2 years after transplantation now. In conclusion, we here report on the first successful liver transplantation in CDG.

From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG).

Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.

Spinal deformity associated with carbohydrate-deficient glycoprotein syndrome (Jaeken's syndrome): a report of three cases.

STUDY DESIGN: Case reports are presented. OBJECTIVE: To report the association between carbohydrate-deficient glycoprotein syndrome Type 1a (CDGS Type 1a) and spinal deformity. SUMMARY OF BACKGROUND DATA: Carbohydrate-deficient glycoprotein syndrome Type 1a is an autosomal recessive metabolic disorder that may occur in association with spinal deformity. METHODS: Analyses of three cases are presented, including a review of the natural history of the disease. RESULTS: Three cases were reviewed in which spinal deformities developed in patients with CDGS Type 1a. Two patients required surgical correction of their spinal deformity, and one patient, at this writing, is undergoing conservative treatment. Before surgery, the pediatric hematology service was consulted regarding the patients' CDGD-related hypercoagulability. Of the two patients who underwent surgical correction, one had severe blood loss (7500 mL), and both cases were treated for infection via intravenous antibiotics. CONCLUSIONS: The incidence of CDGS Type 1a is 1 in 80,0000. Spinal deformity appears to be common in patients with CDGS Type 1a. Therefore, young patients with spinal deformities in combination with mental retardation, failure to thrive, abnormal fat distribution, and other symptoms of CDGS Type 1a should be assessed for this disorder, and patients with CDGS Type 1a should be screened also for spinal deformities. If abnormalities are identified early, treatment outcomes may be optimized.