Beneficial Effect of N-Carbamylglutamate in a Neonatal Form of Multiple Acyl-CoA Dehydrogenase Deficiency

Background. Multiple acyl-CoA dehydrogenase deficiency is an autosomal recessive disorder of the amino acid metabolism and fatty acid oxidation due to the deficiency of the electron transfer protein or electron transfer protein ubiquinone oxidoreductase. The clinical picture ranges from a severe neonatal lethal presentation to late myopathic forms responsive to riboflavin. Up to now, there is no effective treatment for the neonatal form, which exhibits severe metabolic acidosis, hyperammonemia, hypoketotic hypoglycemia, and rhabdomyolysis. We present the case of a child who has had a good long-term outcome after a typical neonatal onset, with a dramatic drop in ammonia levels during the initial metabolic decompensation crisis and adequate control even during intercurrent diseases thereafter with N-carbamylglutamate treatment.

Download Full-text

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: One disease- many faces

10.21203/rs.2.17759/v2 ◽

2020 ◽

Author(s):

Sarah Catharina Grünert ◽

Jörn Oliver Sass

Keyword(s):

Autosomal Recessive ◽

Coenzyme A ◽

Autosomal Recessive Disorder ◽

First Year ◽

Metabolic Decompensation ◽

Term Outcome ◽

Long Term Outcome ◽

Lyase Deficiency ◽

First Year Of Life

Abstract Background 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL . Method We performed a systematic literature search to identify all published cases. 211 patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided. Results More than 95 % of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4 % already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6 % of patients showing normal development. Conclusion This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.

Download Full-text

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: One disease- many faces

10.21203/rs.2.17759/v1 ◽

2019 ◽

Author(s):

Sarah Catharina Grünert ◽

Jörn Oliver Sass

Keyword(s):

Autosomal Recessive ◽

Coenzyme A ◽

Autosomal Recessive Disorder ◽

First Year ◽

Metabolic Decompensation ◽

Term Outcome ◽

Long Term Outcome ◽

Lyase Deficiency ◽

First Year Of Life

Abstract Background 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL .Method We performed a systematic literature search to identify all published cases. 211 patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.Results More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.Conclusion This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.

Download Full-text

Riboflavin Nonresponsive Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) with Early Severe Cardiomyopathy: Favorable Long-Term Outcome of a Severe Neonatal Presentation on D,L-3-hydroxybutyrate Supplementation

10.1055/s-0040-1705557 ◽

2020 ◽

Author(s):

F. Seggewies ◽

L. Guilder ◽

R. Olsen ◽

J. Deanfield ◽

S. Olpin ◽

...

Keyword(s):

Dehydrogenase Deficiency ◽

Term Outcome ◽

Long Term Outcome ◽

Neonatal Presentation

Download Full-text

Long-term outcome of isobutyryl-CoA dehydrogenase deficiency diagnosed following an episode of ketotic hypoglycaemia

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2016.11.005 ◽

2017 ◽

Vol 10 ◽

pp. 28-30 ◽

Cited By ~ 7

Author(s):

S. Santra ◽

A. Macdonald ◽

M.A. Preece ◽

R.K. Olsen ◽

B.S. Andresen

Keyword(s):

Dehydrogenase Deficiency ◽

Term Outcome ◽

Long Term Outcome

Download Full-text

Neurocognitive assessments and long-term outcome in an adult with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2018.06.005 ◽

2018 ◽

Vol 16 ◽

pp. 31-35

Author(s):

Karolina M. Stepien ◽

Philomena McCarthy ◽

Eileen P. Treacy ◽

James J. O'Byrne ◽

Gregory M. Pastores

Keyword(s):

Dehydrogenase Deficiency ◽

Term Outcome ◽

Long Term Outcome

Download Full-text

Smith-Lemli-Opitz syndrome: clinical and biochemical correlates

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0501 ◽

2018 ◽

Vol 31 (4) ◽

pp. 451-459 ◽

Cited By ~ 7

Author(s):

Sarah E. Donoghue ◽

James J. Pitt ◽

Avihu Boneh ◽

Susan M. White

Keyword(s):

Novel Mutation ◽

Cholesterol Biosynthesis ◽

Autosomal Recessive Disorder ◽

Branchial Arch ◽

Term Outcome ◽

Long Term Outcome ◽

Cholesterol Levels ◽

Midline Defects ◽

Opitz Syndrome

AbstractBackground:Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in theDHCR7gene that result in reduced cholesterol biosynthesis. The aim of the study was to examine the biochemical and clinical features of SLOS in the context of the emerging evidence of the importance of cholesterol in morphogenesis and steroidogenesis.Methods:We retrospectively reviewed the records of 18 patients (including four fetuses) with confirmed SLOS and documented their clinical and biochemical features.Results:Seven patients had branchial arch abnormalities, including micrognathia, immune dysfunction and hypocalcemia. Thymic abnormalities were found in three fetuses. All four patients with a cholesterol level of ≤0.35 mmol/L died. They all had electrolyte abnormalities (hyperkalemia, hyponatremia, hypocalcemia), necrotizing enterocolitis, sepsis-like episodes and midline defects including the branchial and cardiac defects. Patients with cholesterol levels ≥1.7 mmol/L had milder features and were diagnosed at 9 months to 25 years of age. All 10 patients had intellectual disability. One patient was found to have a novel mutation, c.1220A>G (p.Asn407Ser).Conclusions:We suggest that screening for adrenal insufficiency and for hypoparathyroidism, hypothyroidism and immunodeficiency, should be done routinely in infants diagnosed early with SLOS. Early diagnosis and intervention to correct these biochemical consequences may decrease mortality and improve long-term outcome in these patients.

Download Full-text