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Diabetic ketoacidosis (DKA) is a life-threatening complication of pediatric diabetes mellitus (DM). A bedside closed-loop artificial pancreas (AP) (STG-55; NIKKISO, Tokyo, Japan) maintains the blood glucose (BG) levels within the target range via automatic infusion of insulin and glucose. We report the application of the closed-loop AP to safely control the BG levels of a pediatric patient with DKA. A 12-year-old child with an unremarkable medical history presented with fever and restlessness. The patient was diagnosed with DKA secondary to fulminant type 1 DM and was treated with insulin infusion. He presented with Glasgow Coma Scale of E2V3M4. Arterial blood gas analysis revealed metabolic acidosis and BG levels of 489 mg/dL. His urine test was positive for ketones. Along with infusion therapy, automatic BG control using a closed-loop AP was initiated after ICU admission. This was adjusted to maintain BG levels within 100 mg/dL/6 h or less. After 24 h in the ICU, the patient regained consciousness and recovered from the metabolic acidosis. His general condition improved, and he was prescribed a diet treatment. The treatment was shifted to continuous insulin infusion, and he was transferred to the general ward, and was discharged on the 33rd day of hospitalization. The closed-loop AP prevented repetitive blood extractions, achieved prompt glycemic control, and prevented cerebral edema in a pediatric patient with DKA. This is the first report of successful treatment of DKA using a bedside closed-loop AP., (© 2022. The Japanese Society for Artificial Organs.)

Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used to aid myocardial recovery in patients with postcardiotomy cardiogenic shock (PCCS), it has been associated with adverse effects. The combined use of VA-ECMO and Impella (ECPELLA) for PCCS, however, has been reported to be efficacious with few reports of thromboembolic events. We present a case of aortic thrombosis with visceral malperfusion during ECPELLA management for PCCS. We performed the Bentall procedure, mitral valve repair, tricuspid annuloplasty, and coronary artery bypass graft on a 73-year-old man admitted with congestive heart failure caused by annuloaortic ectasia, along with severe aortic and mitral regurgitation. VA-ECMO and Impella were required, since the cardiopulmonary bypass weaning was difficult. Impella was removed on postoperative day 4. On postoperative days 5 and 6, laboratory data showed worsening renal dysfunction, lactate levels, and acidosis. Contrast-enhanced computed tomography showed thrombosis in the celiac and superior mesenteric arteries. Aortic thrombectomy was performed. Hyperkalemia, caused by a reperfusion injury, resulted in ventricular fibrillation. Continuous hemodiafiltration improved the hyperkalemia. However, irreversible acidosis progressed, and the VA-ECMO flow rate could not be sustained. On postoperative day 7, the patient died. Perioperative use of Impella for PCCS may be effective in improving postoperative cardiac function. When sudden organ failure is observed after surgery, it is necessary to not only keep the exacerbation of cardiogenic shock in mind, but also the possibility of thrombosis., (© 2023. The Japanese Society for Artificial Organs.)

Functional gastrointestinal disorders (FGIDs) are common in early childhood. It has been demonstrated that neonatal acidemia at delivery can lead to significant neonatal morbidity. The primary aim of this study was to evaluate the relationship between acidemia at birth and the development of FGIDs, as regurgitation, colic, and constipation, in term infants. Term newborns born at the Foggia University Hospital, Italy during the year 2020 were included in the study. As per routine clinical practice, a cord blood gas analysis on a blood sample drawn from the umbilical artery (UA) of each infant immediately after birth was performed, and Apgar score was recorded. One year after birth, each infant's parents were interviewed through a phone call to investigate development of FGIDs, feeding practices, and morbidities. During the study period, 1574 term newborns met the inclusion criteria. The prevalence of infantile colic, regurgitation, and constipation was higher in infants with low UA pH (colic 51.5% vs. 25.4%, p < 0.001; regurgitation 30.6% vs. 15.2%, p < 0.001; constipation 24.6% vs. 16.0%, p = 0.015), with infants having moderate-severe acidemia facing the highest risk for all the examined FGIDs. In binary logistic regression analyses, UA pH and perinatal antibiotic exposure proved to be independently associated with the later diagnosis of each FGID., Conclusion: Newborns with acidemia at birth appear to face a higher risk of FGIDs in infancy. Avoiding low cord blood pH should continue to be the goal for obstetricians, while enhanced long-term surveillance for infants who experienced birth acidemia should be required., What Is Known: • Cord blood gas analysis is recommended in all high-risk deliveries, and in some centers, it is performed after all deliveries. • Neonatal acidemia at birth has been linked to adverse outcomes, mainly neurological. Recently, perinatal asphyxia has been reported to increase the risk of developing necrotizing enterocolitis in term infants., What Is New: • An association between acidemia at birth and risk of developing FGIDs such as regurgitation and colic during the first year of life had never been described so far. • An increased surveillance of infants with low UA pH at birth may be beneficial and could allow for early detection of any of the reported FGIDs., (© 2022. The Author(s).)

Objective: Although sodium bicarbonate (SB) solution has been widely used in clinical practice, its effect on mortality when administered to a large population of patients with acidosis is not known. The study aimed to investigate the effectiveness of SB infusion in septic patients with metabolic acidosis., Methods: Septic patients with metabolic acidosis were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) was used to account for the baseline differences in the probability to receive SB or not. The marginal structural Cox model (MSCM) was employed to adjust for both baseline and time-varying confounding factors., Main Results: A total of 1718 septic patients with metabolic acidosis were enrolled in the study, including 500 in the SB group and 1218 in the non-SB group. Both pH [7.16 (standard deviation (SD): 0.10) vs. 7.22 (SD: 0.07); p < 0.001] and bicarbonate concentration (BC) [11.84 (SD: 3.63) vs. 14.88 (SD: 3.36) mmol/l; p < 0.001] were significantly lower in the SB than that in the non-SB group. While there was no significant mortality effect in the overall population [hazard ratio (HR): 1.04; 95% CI 0.86-1.26; p = 0.67], SB was observed to be beneficial in patients with acute kidney injury (AKI) stage 2 or 3 and pH < 7.2 (HR 0.74; 95% CI 0.51-0.86; p = 0.021). Similar results were replicated with the MSCM., Conclusion: Our study observed that SB infusion was not associated with improved outcome in septic patients with metabolic acidosis, but it was associated with improved survival in septic patients with AKI stage 2 or 3 and severe acidosis. The results need to be verified in randomized controlled trials.

Purpose: To identify peripartum events that may predict the development of short-term neurologic morbidity and mortality among acidemic neonates., Methods: Retrospective case-control study conducted at a single-teaching hospital on data from January 2010 to December 2015. The study cohort group included all acidemic neonates (cord artery pH ≤ 7.1) born at ≥ 34 weeks. Primary outcome was a composite including any of the following: neonatal encephalopathy, convulsions, intra-ventricular hemorrhage, or neonatal death. The study cohort was divided to the cases group, i.e., acidemic neonates who had any component of the primary outcome, and a control group, i.e., acidemic neonates who did not experience any component of the primary outcome., Results: Of all 24,311 neonates born ≥ 34 weeks during the study period, 568 (2.3%) had a cord artery pH ≤ 7.1 and composed the cohort study group. Twenty-one (3.7%) neonates composed the cases group. Multivariate logistic regression analysis revealed that cases were significantly more likely to have experienced placental abruption (OR 18.78; 95% CI 5.57-63.26), born ≤ 2500 g (OR 13.58; 95% CI 3.70-49.90), have meconium (OR 3.80; 95% CI 1.20-11.98) and cord entanglement (OR 5.99; 95% CI 1.79-20.06). The probability for developing the composite outcome rose from 3.7% with isolated acidemia to 97% among neonates who had all these peripartum events combined with intrapartum fetal heart rate tracing category 2 or 3., Conclusion: Neonatal acidemia carries a favorable outcome in the vast majority of cases. In association with particular antenatal and intrapartum events, the short-term outcome may be unfavorable.

Aims/hypothesis: The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk., Methods: A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models., Results: During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m2 (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p trend < 0.0001 and p trend = 0.03, respectively). The NEAP score provided similar findings., Conclusions/interpretation: We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.

Purpose: In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities., Methods: We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT., Results: Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l; p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg; p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min; p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively., Conclusions: Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).

Purpose: The aim was to assess whether impaired cardiac function contributes to symptoms of severe malaria in general or to metabolic acidosis in particular in children living in endemic regions., Methods: In a prospective observational investigation, 183 children with severe malaria were investigated for hemodynamic status and cardiac function upon admission (day 0) and after recovery (day 42). Cardiac function parameters were assessed by cardiac ultrasonography. Blood gas analyses and cardiac enzymes were measured at hospitalization and follow-up. Differences in subgroups with and without metabolic acidosis as well as other severe malaria-defining symptoms and conditions were assessed., Results: Cardiac index (CI) was significantly increased on day 0 compared to day 42 (5.8 ml/m(2), SD ± 1.8 ml/m(2), versus 4.7 ml/m(2), SD ± 1.4 ml/m(2); P < 0.001). CI correlated negatively with hemoglobin levels but not with parameters indicating impaired tissue perfusion or metabolic acidosis. Parasite levels had a significant influence on metabolic acidosis but not on CI. Alterations related to cardiac function, hemoglobin levels and metabolic acidosis were most prominent in children younger than 2 years., Conclusion: Increased CI reflecting high output status is associated with low hemoglobin levels while metabolic acidosis is linked to parasite levels.

In 2006 a case report was published in this journal of a child with known propionic acidemia being diagnosed with the long QT(C) syndrome. This following case documents the first reported case of a child with this condition suffering a life-threatening event from the associated long QT(C) syndrome.

Objective: To investigate the feasibility and the efficacy of expiration under positive pressure (PEP mask) as a chest physiotherapy in patients with exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF) requiring non-invasive positive pressure ventilation (NIPPV)., Design: A prospective, randomised, controlled study., Setting: A respiratory intensive care unit., Patients and Interventions: Twenty-seven patients with large amounts of bronchial secretions on clinical examination due to exacerbation of COPD and mild acidosis were randomly divided into two groups. Group A (13 patients) received PEP mask plus assisted coughing. The controls (group B, 14 patients) received assisted coughing alone., Outcome Measures: The primary end point was to compare total sputum wet weight and to assess the feasibility of the PEP mask. Secondary outcomes were: (a) the time required for weaning patients from NIPPV, (b) treatment failure expressed as mortality within 2 months after discharge from the respiratory intensive care unit (RICU) or the need for endotracheal intubation (ETI)., Results: The amount of sputum production at the end of physiotherapy was significantly ( p<0.01) higher in group A (9.6+/-3.9 g) compared with group B (4.7+/-2.5 g). The total length of weaning time was significantly lower in group A (4.9+/-0.8 days) versus group B (7.0+/-0.7 days), p<0.01. Mortality and ETI were not significantly different in the two groups of patients (0 versus 1 and 0 versus 1, respectively)., Conclusions: Expiration under positive pressure was effective in acutely removing secretions in patients with exacerbation of COPD and mild acidosis requiring NIPPV. In conclusion, we suggest that this chest physiotherapy technique represents a useful therapeutic option for such patients and it should often be performed in addition to NIPPV.

Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

Objective: To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms., Design: Prospective, randomized study., Setting: Surgical intensive care unit (SICU) of a University Hospital., Patients: Fifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control)., Interventions: Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more., Measurements and Results: pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41% and 42% in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p < 0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p < 0.01)., Conclusions: Low pHi values (< 7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient's postoperative course and outcome.

Objective: To determine whether expression of neutrophil integrin receptors is related to the degree of post-traumatic shock., Design: Data were collected prospectively on patients with major trauma admitted to the surgical intensive care unit., Setting: Denver General Hospital, Colorado., Patients and Participants: 17 severely injured adults., Measurements and Results: The mean fluorescence intensity and per cent positive of neutrophil integrin receptors CD11 b, CD18 and CD11 a, and systolic blood pressure, blood transfusion, lactate and base deficit as indices of shock. CD11 b expression on circulating neutrophils was increased 6 and 12 h after trauma. After correcting for the other shock indices, base deficit predicted CD11 b expression at 12 h. CD11 b expression was negatively correlated with the circulating neutrophil count., Conclusions: The degree of metabolic acidosis after trauma correlates directly with CD11 b receptor expression on circulating neutrophils. This relation may be the mechanism whereby post-traumatic shock results in neutrophil sequestration and neutrophil-mediated organ injury and failure.

Systemic and focal cerebral acidosis is considered deleterious to cell metabolism and neuronal recovery. We investigated the immediate effect of tris-(hydroxymethyl)-aminomethane (THAM), an alkalizing agent, on focal cerebral ischemia produced by occlusion of the left middle cerebral artery (MCA) in cats with systemic acidosis. Occlusion of MCA resulted in prompt decreases in local cerebral blood flow of the ipsilateral marginal and ectosylvian gyri from 47.7 ml/100 g per minute in control to 32.3 ml/100 g per minute and 8.3 ml/100 g per minute, respectively. In the control group, physiological saline was infused continuously and the treated group received 0.3 M THAM to normalize systemic and focal cerebral acidosis. There were no significant changes in the systemic arterial pressure, arterial PO2 and PCO2 throughout the experiments in the two groups. Arterial pH decreased from 7.42 to 7.30 in the control, while it remained normal during THAM treatment. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.39 to 6.87 with 6 h ischemia in the control group. In THAM infusion, extracellular pH was kept between 7.26 and 7.29, which was significantly higher than the control group. THAM significantly decreased infarct volume and lactate and water contents of the gray matter in the marginal gyrus at 6 h after occlusion. It is concluded that THAM infusion immediately after ischemia onset is considered effective in improving acidosis at the site of ischemic penumbra and consequently reduces lactate production, brain edema, and infarct volume.

Forty ICU patients were studied as to the prevalence and importance of organic acidaemia. It was observed that organic acidaemia was extremely common, secondly that a persistence of such an acidaemia heralded a poor prognosis and finally that the acidaemia rarely needed treatment in its own right.

Prostaglandin E1 (PGE1) infusion was used in 7 infants with hypoplastic left ventricle and aortic atresia. Of 5 non-operated patients, 4 died shortly after the onset of PGE1 infusion and 1 survived for 30 hours. Of the infants who had surgery, 1 died during the operation and 1 survived for 38 days. In 6 infants, a transient metabolic and/or circulatory improvement could be demonstrated following PGE1 infusion. The lack of response of other infants may be related to the advanced deterioration of their clinical status at the time of study. In the light of recent surgical developments for infants with aortic atresia, support with PGE1 may nevertheless play an important role in their management if started early.

Seventeen infants under 2 months of age are described who presented with methaemoglobinaemia and acute diarrhoea during a period of 2 years. No infants beyond this age presented with such characteristics. In none of them was one of the known mechanisms of methaemoglobin formation found. All infants recovered with conventional therapy. Methaemoglobin associated with diarrhoea relapsed in three infants before they were 2 months old. Twenty-six similar cases have been reported in the literature. The mechanism of methaemoglobinaemia in these infants is unclear.

Four cases of candidal arthritis and osteomyelitis are presented and 17 others are reviewed from the literature. The clinical and radiographic aspects of the entity are discussed in detail and compared with those of bacterial septic arthritis. The role of predisposing factors are elaborated. An increase in the incidence of the disease is anticipated and the diagnostic difficulties are enumerated.

The biochemical and therapeutic responses to dietary therapy were studied in a 25-month-old girl and a 1-month-old girl with methylmalonic acidemia (MMA-emia), which was unresponsive to vitamin B12. The minimum daily intake of protein which patients could tolerate and display a good development was between 1.0 and 1.2 g per kg body weight. Supplementation with amino acid mixture devoid of toxic amino acids was required to prevent protein malnutrition when daily protein intake was restricted to 0.6 g per kg body weight. Caloric intake should be sufficient, not only to promote growth but also to prevent a rise in MMA level, especially when a patient has ketoacidosis. It was found that MMA excretion per mg creatinine in random urine specimens correlated significantly with serum MMA and twenty four-hour output of MMA per kg body weight. Therefore measurement of MMA in a single urine specimen is useful for evaluating the in vivo accumulation of MMA.

Two cases of D-lactic acidosis associated with short bowel syndrome are described. The administration of kanamycin to the patients showed a decrease in D-lactate in blood and urine in parallel with disappearance of metabolic acidosis. Bacteriological analyses of the fecal flora showed an increase in Lactobacillus buchneri in the first patient and Lactobacillus fermenti IVa in the second; both bacteria were sensitive to kanamycin. Quantification of in vitro production of D-lactate by each species of bacteria isolated from the feces revealed that Lactobacillus produced more D-lactate than other species of bacteria. These observations indicate that Lactobacillus may play an important role in the induction of D-lactic acidosis in patients with short bowel syndrome.

A 16-month-old female infant with severe mental and motor retardation, clinically diagnosed as Leigh's encephalomyelopathy, forms the basis of this study. This infant was found to have lactic acidosis, low cerebrospinal fluid glucose, hyperalaninemia, and increased levels of urine lactate, pyruvate and alanine. These laboratory studies suggested an inborn error in gluconeogenesis. Further investigation revealed a low level of hepatic pyruvate carboxylase activity. The patient's elder sister who also had mental and motor deterioration was then also found to have an elevated blood lactate. These two siblings clinically and biochemically showed improvement with treatment consisting of thiamine and lipoic acid.

Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone.

A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.