HMG–CoA Lyase Deficiency

Puisac, Beatriz; Arnedo, María; Gil-Rodríguez, Ma Concepción; Teresa, Esperanza; Pié, Ángeles; Bueno, Gloria; Ramos, Feliciano J.; Gómez‐Puertas, Paulino; Pié, Juan

doi:10.5772/20252

Cited by 4 publications

(1 citation statement)

References 77 publications

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“…Background 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency is a rare autosomal recessive disorder which impairs ketogenesis and leucine catabolism (1). Episodes of metabolic decompensation occur during physiologic stress (e.g.…”

Section: Learning Pointsmentioning

confidence: 99%

First report of type 2 diabetes mellitus in an adult with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency

Lai

Shahidi

Chan

et al. 2023

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency is an inborn error of metabolism resulting in a lack of ketogenesis and leucine catabolism. Hallmarks of decompensation include hypoglycemia without ketosis (or hypoketosis), metabolic acidosis, and hyperammonemia. Management includes avoiding fasting and restricting dietary protein and fat. Conversely, type 2 diabetes mellitus (T2DM) requires carbohydrate restriction and/or anti-hyperglycemic agents; thus, managing these co-existing disorders is challenging. A 36-year-old male with HMG-CoA lyase deficiency and T2DM (Hemoglobin A1c (HbA1c): 7.9%) presented with confusion and shock. Blood work revealed metabolic acidosis, hyperammonemia, hyperglycemia, and hypoketosis. The patient was diagnosed with hyperosmolar non-ketotic hyperglycemia and hyperammonemia secondary to HMG-CoA lyase metabolic decompensation requiring intensive care unit admission. Hyperammonemia management was challenging because alternative calories with i.v. dextrose (due to hyperglycemia) and i.v. lipids (due to HMG-CoA lyase deficiency) could not be provided as usual. The patient was started on hemodialysis and i.v. insulin with marked improvement. Once stabilized, metformin and insulin were initiated. T2DM impaired cellular glucose uptake and produced a state similar to hypoglycemia, despite the patient being profoundly hyperglycemic, which led to metabolic decompensation of HMG-CoA lyase deficiency. Managing T2DM and HMG-CoA lyase deficiency warrants special considerations due to the potential for metabolic decompensation with both hyperglycemia and hypoglycemia. Learning points In a patient with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency and type 2 diabetes mellitus (T2DM), management principles include avoiding hypoglycemia to prevent metabolic decompensation, providing insulin for proper glucose utilization, and moderation of carbohydrate intake to prevent consequences of chronic hyperglycemia. The development of insulin resistance in the form of T2DM in HMG-CoA lyase deficiency likely triggered a state similar to hypoglycemia, leading to cellular energy deficiency and subsequently metabolic decompensation. It is important to avoid hypoglycemia in patients with HMG-CoA lyase deficiency and T2DM, as the risk of metabolic decompensation is increased due to the lack of ketogenesis in HMG-CoA lyase deficiency. Selection of antidiabetic agents in this patient population requires careful consideration, and agents that have a higher risk of hypoglycemia should be avoided.

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Section: Learning Pointsmentioning

confidence: 99%

First report of type 2 diabetes mellitus in an adult with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency

Lai

Shahidi

Chan

et al. 2023

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Dietary therapy for a patient affected with 3-hydroxy-3-methylglutaric aciduria

Tong

Weng

Liu

et al. 2014

Tzu Chi Medical Journal

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Congenital disorders of glucose metabolism in adults with nondiabetic hypoglycemia

Yukina,

Troshina,

Nuralieva

et al. 2024

Obes. metabol.

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BACKGROUND: Recent clinical descriptions have shown that in adult patients, the cause of nondiabetic hypoglycemia (NDH) may be various genetically determined disorders of glucose metabolism or insulin synthesis/bioavailability. In this connection, in adult patients with NDH of unclear genesis, it is important to conduct a genetic study in order to search for mutations in genes associated with congenital disorders of glucose metabolism (CDGM).AIM: To evaluate the effectiveness of genetic testing to exclude CDGM in adult patients with idiopathic NDH.MATERIALS AND METHODS: Based on the analysis of the literature, a targeted panel has been developed, including 30 genes, mutations in which are associated with the following groups of diseases: 1) congenital hyperinsulinism (KCNJ11, ABCC8, GLUD1, HADH, UCP2, HNF4A, HNF1A, GCK, INSR, SLC16A1); 2) glycogen storage diseases (AGL); 3) other carbohydrate metabolism disorders (ALDOB, FBP1); 4) glycosylation defects (PMM2, ALG3, PGM1, MPI); 4) defects in fatty acid oxidation (ACADM, ETFA, ETFB, ETFDH, FLAD1, SLC25A32, SLC52A1, SLC52A2, SLC52A3); 5) disorders of ketone body metabolism (CPT1A, CPT2, HMGCL); 6) mitochondrial disorders (DLD). Twenty nine patients (n=29: with idiopathic NDH n=17 and with insulinoma n=12) aged 19 to 66 years underwent a genetic study using this custom panel.RESULTS: As a result of the examination 12 genetic variants (all heterozygous) were identified in 8 patients with idiopathic NDH (47%, 95% CI (23%; 72%)), at that two mutations were detected in three patients: in the genes AGL and HMGCL; ACADM and FLAD1, respectively; and one patient had three mutations: one mutation in the ETFA gene and two mutations in the ABCC8 gene. Frequencies of genetic variants: AGL — 18%, 95% CI (4%; 43%), ETFA — 12% (1%; 36%), HMGCL — 6% (0%; 29%), ALDOB — 6% (0%; 29%), CPT1A — 6% (0%; 29%), ABCC8 — 6% (0%; 29%), ACADM — 6% (0%; 29%), FLAD1 — 6% (0%; 29%). 5 genetic variants (all heterozygous) were identified in 5 patients with insulinoma (42%, 95% ДИ (15%; 72%)). Frequencies of genetic variants: ABCC8 — 17%, 95% CI (2%; 48%), HNF1A — 8% (0%; 38%), ETFDH — 8% (0%; 38%), MPI — 8% (0%; 38%). We did not include benign variants in this analysis. At the same time, clinically significant variants were identified only in one patient from the group with idiopathic NDH (6%, 95% CI (0%; 29%)) in the ABCC8 gene and in one patient from the group with insulinoma (8%, 95% CI (0%; 38%)) in the same gene congenital hyperinsulinism (CHI).CONCLUSION: A panel of 30 genes has been developed, variants of which are associated with a CDGM. The results of our study confirm the possibility of detecting CDGM in adulthood, in particular CHI, and indicate the need for genetic testing, primarily in patients with idiopathic NDH.

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HMG–CoA Lyase Deficiency

Cited by 4 publications

References 77 publications

First report of type 2 diabetes mellitus in an adult with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency

First report of type 2 diabetes mellitus in an adult with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency

Dietary therapy for a patient affected with 3-hydroxy-3-methylglutaric aciduria

Congenital disorders of glucose metabolism in adults with nondiabetic hypoglycemia

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