A patient suffering froma mitochondrial myopathy leading to severe insufficiency of the voluntary muscles is described. Severe cerebral damage was present. Major biochemical symptoms were extreme lactic acidemia, hypophosphatemia and hyperphosphaturia, and generalized aminoaciduria, renal glucosuria, and polyuria. Muscular insufficiency resulted in lethal asphyxiz. All therapeutic trials were insufficient. The patient and two other children of the same family with a similar clinical picture all died before the 4th month of life. The condition is probably inherited in an autosomal recessive way. A defective respiratory chain in the mitochondria of the striated muscles is proposed as the underlying mechanism. Cytochromes aa3 were absent, b was nearly absent, but cc1 was present. In heart muscle cytochromes aa3 and b were at the level of the controls.

Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.

A mentally retarded male infant with persistent hyperlysinaemia due to L-lysine alpha-ketoglutarate reductase deficiency is described. The effect of dietary restriction of lysine on his mental and behavioural development was examined. By restricting daily dietary lysine to 5.5 mg/kg body weight the fasting serum lysine became normal. Urinary lysine also became normal and the secondary metabolites homocitrulline, homoarginine, N alpha-acetyllysine and N epsilon-acetyllysine were no longer detected. After control of serum lysine for 2.5 y it was felt that the patient's social behaviour, but not his mental development, had improved somewhat.

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SummaryA new case of glucosephosphate isomerase deficiency is described in a Dutch family. The activity of the enzyme was decreased to 20-25s of the normal value. Characterization of the defect enzyme showed a pronounced thermolability.Heating of the enzyme at 45°C showed a loss of activity of 90% after one hour. The pH-optimum and the electrophoretic migration were normal. The KV-value for F-6-P, the Ki for the competitive inhibitors 2,3-DPG and 6-PG were in the normal range. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name of GPI-Utrecht.

Gas-liquid chromatography, combined with mass spectrometry, is a powerful tool in studying inborn errors of metabolism, but this technique only gives the molecular structure of compounds and does not give information about the absolute configuration. We were confronted with a mentally retarded patient with severe lactic aciduria (up to 100mmol/l) and normal blood lactate concentration. Knowledge of lactate metabolism could not explain this phenomenon, as normally occurring L-lactate has a renal threshold of 7 mmol/1, and there was no evidence of renal dysfunction in this patient. Therefore a method was developed for the separation of the optical isomers by means of capillary gas chromatography° After ethylacetate extraction the acid was esterified with optically active (-)-menthol and the hydroxylgroup was acetylated. Subsequent capillary gas-chromatography on a SP-1000 column (25m x 0.3mm) at 150°C gave a good separation of the enantiomers (Kamerling et al., 1976). The urinary lactate in this patient proved to be almost exclusively the D-isomer. In the patient's blood and CSF both isomers were present in equal amounts. The cause of this abnormal D-lactic aciduria is still under investigation.The method was also applied in a patient with glyceric acidaemia. The isolated glyceric acid was converted into its di-O-acetyl menthyl ester. This time capillary gas-liquid chromatography was done at 200 °C. Both blood and urinary glycerate had the D-configuration. Some evidence was obtained that the accumulation of D-glyceric acid in our patient was due to an abnormality in the metabolism ofserine (Wadman et al., 1976).

In a patient with the clinical symptoms of Leigh's disease a partial deficiency of hepatic pyruvate carboxylase and pyruvate decarboxylase was found at necropsy. Cerebral pyruvate decarboxylase activity was also diminished. All enzyme activities were measured in total homogenates. The finding of typical necrotic lesions in the brain stem was consistent with the clinical diagnosis. During life moderate lactic acidaemia and no hypoglycaemia were observed, but an abnormal organic acid excretion pattern was present. The contribution of the enzyme defects to the aetiology of the disease is discussed.

SUMMARY A patient suffering from severe lactic acidaemia due to pyruvate carboxylase deficiency is presented. The clinical picture is different from the full‐blown Leigh's disease. The child had severe mental retardation, muscular hypotonia and abundant subcutaneous fat. As could be expected in defective neoglucogenesis, hypoglycaemia was provoked by prolonged fasting. Besides high urinary concentrations of lactic acid, increased concentrations of malic, fumaric, succinic and α‐ketoglutaric acids were observed. All therapeutic attempts towards treatment of the severe hyperlactacidaemia have been unsuccessful. RÉSUMÉ Un patient souffrant d̂une lactacidŕmie grave provoquŕe par un dŕficit en pyruvatecarboxylase est prŕsentŕ. Le tableau clinique est diffŕrent de celui de la maladie de Leigh floride. Une arriŕration mentale sŕvŕre, une hypotonie musculaire et une accumulation excessive de graisse souscutanŕe etaient prŕsentes. Comme on pourrait s'attendre lors d̂une trouble de la nŕoglucogŕnèse une hypoglycŕmie ŕtait provoquŕe par une pŕriode de jeûne prolongŕe. A cotŕ d̂une excrŕtion urinaire massive d̂acide lactique des concentrations ŕlevŕes d̂acide malique, fumarique, succinique et α‐cŕtoglutarique ŕtaient prŕsentes. säure Fumarsäure, Bernsteinsäure und α‐ketoglutarsaure festgestellt. Toutes les mesures thŕrapeutiques, visant à diminuer la lactacidŕmie, ont ŕchouŕ. ZUSAMMENFASSUNG Ein Patient mit schwerer Milchsäureäzidamie infolge Pyruvat Carboxylase Mangels wird beschrieben. Das klinische Bild unterscheidet sich von der komplett entwickelten Leigh Krankheit. Eine schwere geistige Unterentwicklung, Muskelschwäche und starke subkutane Fettbildung wurden festgestellt. Wie erwartet im Fall einer mangelhaften Gluconeogenese, wurden Hypoglykämien durch längeres Fasten verursacht. Im Urin wurden, neben hohen Milchsäurekonzentrationen, erhöhte Konzentrationen von Apfelsaure, Alle therapeutische Ma ßnahmen in der Behandlung dieser schweren Hyperlaktatazidämie waren nicht erfolgreich. RESUMEN Puciente con acidemiu láctica crónicu grave y deficencia de piruvato carboxitasa Se describe un paciente que sufría de acidemia láctica grave debido a una deficiencia de piruvato carboxilasa. El cuadro clinico es diferente de la enfermedad de Leigh. Presentaba un retraso mental grave, hipotonía muscular y una abundante grasa subcutánea. Tal como podia esperarse en un defecto de la neoglucogŕnsis, la hipoglicemia era provocada por un ayuno prolongado. Además de una alta concentración urinaria de ácido Iáctico, se observó un aumento en la concentración de los ácidos málico, fumárico, succínico y α‐cetogiutarico. Todas las tentativas terapŕuticas encaminadas al tratamiento de la hiperlactacidemia grave no han dado resultado.