| Description |
Deficiency of cytosolic glycerol-3-phosphate dehydrogenase (GPD1, EC 1.1.1.8) manifests in infancy with hepatomegaly, moderate to severe hypertriglyceridemia and cholestasis resulting in steatosis and fibrosis but the course of the disease seems to be non-progressive and relatively be nign . Among 17 patients described so far, severe liver disease was found in one patient only. We report infantile hypertriglyceridemia/GPD1 deficiency (OMIM #614480) in nine Roma children and one boy of Palestinian Arab origin. The main symptoms included, early onset mod erate to severe hepatomegaly (9 of 10 patients), hepatopathy (AST 63,600–309,600 IU/ml, controls<58,200; ALT 35,500–151,200 IU/ml, controls<51,200; GGT 57,600- 1,416,000 IU/ml, controls<62,400) and hypertriglyceridemia (189–1062 mg/dl, controls 44–195). Coagulation tests and extensive serologic and metabolic analyses were normal except for mild repeated hypoglycemia (50.5–55.9 mg/dl, controls 70.2–100.9) in two infants. The children are now between 2 and 17 y old, and they are of low-normal growth. All our Roma patients were homozygous for a novel mutation c.895G>A (p.Gly299Arg), the boy of Palestinian Arab origin was homozygous for a novel mutation c.116G >A (p.Trp39*) in GPD1. The mutations were not found in the GnomAD database and were predicted to be pathogenic. The pathogenicity of the c.895G >A substitution was supported by the absence of homozygosity in patient’s healthy siblings and parents. Our results indicate a high frequency of the mutation in the Roma population, probably due to the founder effect. Although the clinical and laboratory features stabilized or improved in children with no signs of liver failure, liver biopsy performed in six patients revealed combined micro/ macrovesicular steatofibrosis and even signs of transition to cirrhosis in two boys. Such an early development of cirrhosis in some children opposes the current conception of GPD1 being a benign or transient disease. Therefore we suggest that the original name of the disease “transitory infantile hypertri- glyceridemia” be abandoned and replaced by “GPD1 deficiency”. As there are no specific biochemical markers for GPD1 deficiency except for elevated aminotransferases and triglycerides (typically without hypercholesterolemia), the underdiagnosis of GPD1 deficiency is very probable in children or adolescents with hepatomegaly and/or hepatopathy of unknown origin or non-alcoholic steatohepatitis (NASH).
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