Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of... more Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long‐chain fatty‐acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 m...
Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of... more Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long‐chain fatty‐acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 m...
Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast ... more Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast cultures of 19 patients with congenital disorders of glycosylation (CDG) of different subtypes. A constant finding in liver biopsies of all CDG‐I cases was that of abnormal lysosomal lamellar inclusions in the hepatocytes, which were not found in CDG‐II. None of the patients showed significant abnormalities in their fibroblasts.
Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast ... more Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast cultures of 19 patients with congenital disorders of glycosylation (CDG) of different subtypes. A constant finding in liver biopsies of all CDG‐I cases was that of abnormal lysosomal lamellar inclusions in the hepatocytes, which were not found in CDG‐II. None of the patients showed significant abnormalities in their fibroblasts.
Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐li... more Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐N‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotsp...
Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐li... more Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐N‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotsp...
Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of... more Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long‐chain fatty‐acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 m...
Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of... more Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long‐chain fatty‐acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 m...
Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast ... more Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast cultures of 19 patients with congenital disorders of glycosylation (CDG) of different subtypes. A constant finding in liver biopsies of all CDG‐I cases was that of abnormal lysosomal lamellar inclusions in the hepatocytes, which were not found in CDG‐II. None of the patients showed significant abnormalities in their fibroblasts.
Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast ... more Summary: We report a retrospective electron‐microscopical study of liver biopsies and fibroblast cultures of 19 patients with congenital disorders of glycosylation (CDG) of different subtypes. A constant finding in liver biopsies of all CDG‐I cases was that of abnormal lysosomal lamellar inclusions in the hepatocytes, which were not found in CDG‐II. None of the patients showed significant abnormalities in their fibroblasts.
Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐li... more Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐N‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotsp...
Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐li... more Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐N‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotsp...
Uploads