3‐Hydroxy‐3‐methylglutaryl‐coenzyme A lyase deficiency: A review

Abstract

Children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA-LD; McKusick 24645), have inherited two areas of metabolic weakness. Firstly, they are unable to metabolize fully the carbon skeleton of leucine, and secondly, they cannot make ketone bodies in response to prolonged fasting. In the first year of life infants with HMG-CoA-LD run a high risk of developing severe hypoglycaemia which can lead to death if prompt intervention does not occur. The metabolic crisis develops when the infant is first introduced to dietary protein soon after birth, or later, when a reduced intake of glucose, often during a viral infection, results in a drain on the infant's circulating glucose levels. However, where diets are adequately adjusted to limit protein and fat intake, the metabolic handicaps of individuals with HMG-CoA-LD are not exposed and they are virtually symptomless. As children with HMG-CoA-LD grow older the incidence of hypoglycaemic attacks diminishes and they usually develop normally. This article reviews literature on cases of HMG-CoA-LD and interprets data on altered metabolism in these children.

Chemical Diagnosis of Inherited Defects of Fatty Acid Metabolism and Ketogenesis

“…To date we have diagnosed 7 cases. Patients present with in termittent attacks of severe nonketotic hypo glycemia under conditions of prolonged fast ing [29]. Our experience with this disorder showed that a fair number of patients died in childhood; we also observed permanent brain damage following an attack.…”

HMG–CoA Lyase Deficiency

“…(Schutgens et al, 1979;Gibson et al, 1988a;Gibson et al, 1988b). In some cases the progresive lowered state of consciousness leads to coma and subsequent death (Wysocki et al, 1986). Laboratory data that stand out are the metabolic acidosis and non-ketotic hypoglycemia (Table 1).…”

Mitochondrial HMG–CoA Synthase Deficiency

“…In the latter, most of the patients show muscular weakness and myopathy (Ribes et al, 2003). In the HL deficiency symptoms as dehydration, hypotonia, hypothermia, tachypnea, lethargy, coma and even death, have been reported (Wysocki & Hahnel, 1986;Menao et al, 2009). Up to date, no patient with mHS deficiency has died due to this disease.…”