d‐Glyceric acidaemia: clinical report and biochemical studies in a patient

Abstract

D-Glyceric acidaemia is a very rare inherited metabolic disorder and clinical and biochemical presentations are quite heterogeneous. Regarding the clinical features, the patients can be divided into three groups: severe encephalopathy, sometimes with hyperglycinaemia; moderate clinical symptoms (i.e. moderate mental retardation or speech delay), metabolic acidosis and microcephaly; or the absence of clinical problems. Biochemical investigations performed in these patients have suggested disturbed fructose or/and serine metabolism.We have previously described (Fontaine et al., 1989) biochemical investigations in a patient with D-glyceric acidaemia in whom a deficiency of D-glyeerate kinase has been demonstrated (Van Schaftingen, 1989). We report here the clinical presentation of the child, other biochemical studies and the results of a therapeutic trial with sodium benzoate.The patient, a girl (C.E.), was the first child of healthy Turkish first cousin parents. She was born after an uneventful pregnancy and delivery, with birth weight 2480 g, length 47cm and head circumference 31cm. At 2 months of age the patient was noted to be hypertonic and had feeding difficulties. At 8 months of age she was referred for evaluation of delayed psychomotor development and poor weight gain. On admission, her body weight was 5500g (-2.5 SD), length 57cm (--4 SD) and head circumference 39.5cm (-3 SD). Clinical examination showed severe axial hypotonia and hypertonia of the limbs. At that time the child had never had seizures or other abnormal movements. Psychomotor development was at a 2-month level. She did not have dysmorphic features or hepatosplenomegaly. EEG, CT scan of the brain, visual and somesthetic evoked potentials were normal. On the other hand, brainstem evoked potentials showed severe alterations of central components.Laboratory investigations, including amino acid determination in plasma, urine and CSF, did not show any abnormality except for a sideropenic anaemia. Acidosis was not present. The only abnormal finding was the presence of D-glyceric acid in urine, plasma and CSF.At 1 year of age, the patient had for the first time generalized seizures successfully treated with sodium valproate. She presented several times with attacks of painful hypertonia and opisthotonos, successfully treated with diazepam. The child is now 3 years old; she has severe spastic tetraplegia, profound encephalopathy and hypotrophy.D-Glyceric acid, a compound normally not detected in control subjects, was 1Service de Prdiatrie et Grnrtique Mrdicale and 3Laboratoire

D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK)

“…While liver activities of D-glycerate dehydrogenase and triokinase were normal, van Schaftingen [1989] demonstrated deficiency of hepatic D-glycerate kinase in a patient with D-glyceric aciduria described by Fontaine et al [1989] and Largillière et al [1991]. However, confirmation of that finding in other individuals with D-glyceric aciduria was never reported.…”

D-Glyceric Aciduria in a Six-Month-Old Boy Presenting with West Syndrome and Autistic Behaviour

“…Fructose and serine loading tests resulted in a deficiency of Dglycerate kinase, indicating the potentially benign nature of the disease. Largillire et al [9] described a 3 year-old Turkish girl with profound encephalopathy, spastic tetraplegia and hypotrophy in whom a therapeutic trial with sodium benzoate decreased plasma D-glycerate without any clinical improvement and concluded that D-glyceric aciduria can only be a biochemical finding without any causal relationship with the various pathological symptoms associated with it.…”