Discussion: Very few cases of late onset optic neuropathy and neurosensory hearing loss associated with MMA have been reported, and a morphological correlate in MRI scans has not been documented before. Impaired mitochondrial function is suspected to be the underlying cause of bilateral optic atrophy and neurosensorial hearing loss in MMA, although the pathophysiology is not well understood. Managing late-onset or long term complications of metabolic disease is a central issue in the care of adult patients with inborn errors of metabolism. Methyl malonic aciduria (MMA) is a disease caused by a deficiency in the enzyme, methyl malonyl CoA mutase, which is responsible for the metabolism of branched-chain amino acids. MMA is generally characterised by attacks of ketosis, acidosis, nausea, vomiting, dehydration, lethargy and increased concentrations of methyl malonic acid in blood and urine. Patients with MMA are initially treated with vitamin B12, with those who do not respond placed on diets containing limited amounts of protein and branched-chain amino acids. Patients with uncontrolled MMA or infections due to catabolic stress may have skin lesions, specifically generalized exfoliative eruptions, a condition called acrodermatitis dysmetabolitica. These cutaneous eruptions are characterized by a deficiency in isoleucine, one of the eseential amino acids. We encountered a patient on an amino acid restricted diet who experienced skin lesions caused by a lack of isoleucine (plasma concentration, 4.71 μmol/L). Within days of liberalizing his restricted diet and after supplementation with 100 mg/kg/day isoleucine, the eruption resolved completely. We present two patients aged four years and fourteen years with methylmalonic acidaemia who were admitted to intensive care with severe metabolic decompensation. Both patients have end stage renal failure and are on the renal transplant list. The children's renal function had significantly deteriorated with the decompensation and both went on to receive haemodialysis while on intensive care. We present data to demonstrate the effect of dialysis on the MMA levels and correlate the levels with the progression of renal recovery. This data is of interest because it is assumed that MMA has a direct nephrotoxic effect, as patients with propionic acidaemia do not have renal disease as a complication while sharing other similarities with MMA. These cases raise the questions: (i) Does haemodialysis aid renal recovery at times of decompensation by offloading the effect of MMA on the kidneys (ii) Should we utilise MMA levels more in the management of MMA patients both when well and decompensated? (iii) Are there other biochemical parameters that can be linked with MMA levels, e.g. acylcarnitine profiles? Background: Short stature and low GH levels have previously been reported in patients with methylmalonic aciduria. Diagnosis of GH deficiency is usually based on GH response to a provocative stimulus like glucagon. Case Report: We describe a boy with vitamin B12 non-responsive methylmalonic aciduria. He presented in the neonatal period with intrauterine growth retardation and metabolic acidosis and following diagnosis was treated with carnitine and a low protein diet. He had mildly delayed developmental milestones. His renal function was deceased but stable with a glomerular filtration rate of 60 ml/min/1.73 m2. Despite satisfactory progress with infrequent metabolic decompensation, growth remained poor in the face of adequate nutrition. Coeliac screen, thyroid function, prolactin were normal but plasma arginine and Insulin-like growth factor (IGF1) were low. His bone age was normal for his chronological age. Glucagon stimulation test showed a sub-optimal response of GH in contrast to the arginine stimulation test which produced a good response with a sufficient peak of GH (21.4mcg/L). Treatment with arginine was initiated. Early follow up showed an improved height velocity and normalisation of his IGF1. Conclusion: In patients on protein restricted diets with faltering growth arginine levels should be measured and supplementation considered if low. Methylmalonic aciduria cblB type is due to mutations in the MMAB gene which encodes the ATP:cobalamin adenosyltransferase enzyme. We describe two siblings with identical genotype and different biochemical phenotype one detected through expanded newborn screening and classified as cblB type by somatic cell complementation. He presented deficient propionate uptake rescued after cellular B12 treatment. He was compound heterozygous for two novel variant changes p.H183L (c.287 T>C) and p.R190dup (c.568-570dup). The subsequent familiar genetic analysis revealed that his clinically asymptomatic sibling, nine years old, presented also both variant changes. She exhibited only mild excretion of MMA and close to normal propionate uptake. Functional analysis revealed that p.H183L mutant protein had specific activity and affinity parameters similar to wild-type. It is noticeable that the efficiency of expression and purification was nearly 70-fold lower that wild-type ATR and also had a high reduced stability compared to wild-type indicating that it is likely a new destabilizing mutation in the MMAB gene. Mutant protein p.R190dup was highly unstable and the specific activity was undetectable. The structural and functional analyses suggest that both mutations are likely disease-causing, but there must be an additional genetic defect in MMAB or phenotypic modifiers genes to explain the different phenotype. Women with methylmalonic acidemia may be at risk of metabolic acidosis, hyperammonemia or renal failure in the postpartum period. We describe the course and outcome of a pregnancy in a patient with methylmalonic acidemia due to Cobalamin-B-deficiency and a chronic renal failure caused by the underlying disease. Methylmalonic acidemia was diagnosed at 5 months of age; Cobalamin-Bdeficiency was genetically confirmed at the age of 26 years. Pregnancy occurred at the age of 27 years. Her long-term treatment consisted of the protein restricted diet, supplementation of isoleucine-methioninethreonine-valine-free amino-acid mixture, L-Carnitine and intramuscular application of Hydroxycobalamin (10 mg/every other week). During pregnancy the treatment was continued and control visits at the centre intensified. Her renal function was stable and the urinary excretion of methylmalonic acid decreased from 1600 to 477 mmol/mol Creatinine in the third trimenon. At term a healthy male infant was born spontaneously.