Porphyria variegata (PV, OMIM 176200), is caused by a partial deficiency of protoporphyrinogen oxidase (PPOX, E.C. 1.3.3.4.) and its clinical manifestations include acute neurovisceral attacks and/or cutaneous photosensitivity. Biochemical diagnosis of PV is based on abnormal fecal porphyrin profile, fluorometric plasma scan, and increased urinary levels of porphyrin precursors during an acute attack. In this study, the PV diagnosis was determined in index patients from 9 unrelated Jewish families on the basis of clinical symptoms and biochemical findings. DNA analysis revealed 5 mutations in the PPOX gene, four novel (p.Trp42X, p. Gly187Arg, p.His333Arg, p.Ala466Glu), mutation p.Val84Gly has been previously described. Mutation p.His333Arg was found in five unrelated families, the remaining mutations were specific only for the individual family. All families with mutation p.His333Arg are from Morocco, the mutation might be a founder one in Moroccan Jewish population. This mutation was not found in DNA samples of healthy unrelated controls of Moroccan Jewish origin (n=280) and Ashkenazi Jewish origin (n=330). The identification of the asymptomatic family members will reduce risk of PVonset by avoiding triggering factors. Erythropoietic protoporphyria (EPP) is characterized by excess accumulation of protoporphyrin, particularly in the erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In majority of EPP patients, clinical expression requires coinheritance of a private FECH mutation trans to a hypomorphic FECH*IVS3-48 C allele. This leads to decrease of FECH activity below threshold of cca 35%. Clinical manifestations of the disease are characterized by cutaneous photosensitivity in early childhood (burning, itching, swelling, and redness) in sun-exposed areas. Hepatic failure occurs in some patients (about 1-10% of EPP patients) which may necessitate liver transplantation (www.porphyria-europe.com; Lancet, 375: 924-937, 2010) . We investigated mother and son of Czech origin with manifest EPP and 7 members of their family in 4 generations and found a novel mutation in the FECH gene in 4 individuals including probands (G→A transition at position 84 in exon 2; W28X, located in a mitochondrial targeting sequence). Both clinically manifest probands (in son, recently, a liver transplantation was performed) inherited a hypomorphic allele as well, while two clinically latent individuals with FECH mutation did not. (Supported by grants # 1 M0520 and MSM 0021 620806 from MSMT of Czech Republic) P-543 Cerebrotendinous xanthomatosis (CTX) is a progressive neurodegenerative disorder caused by mutations in CYP27A1, the gene encoding sterol 27 hydroxylase. The enzymatic block leads to abnormal production of cholestanol, a toxic cholesterol derivative that accumulates in peripheral tissues and brain. Although treatment with chenodeoxycholic acid (CDCA) has been used for more than 25 years to stabilize or improve clinical manifestations, evidence of efficacy comes solely from isolated case reports and small clinical studies. Here, by using magnetic resonance spectroscopy (MRS), we show unambiguously from the follow up of 7 patients only, that treatment with CDCA improves brain function, as reflected by a significant and gradual decrease in the white-matter choline/ creatine and choline/NAA ratios. This improvement in spectroscopic parameters was accompanied by a significant improvement in the Mini-Mental State Examination (MMSE) score and in some nerve conduction velocities. These findings indicate that MRS can be used as an objective quantitative method for monitoring treatment efficacy in small groups of patients with rare neurological disorders. Several mutations in mitochondrial transfer RNA genes cause mitochondrial myopathy. The mtDNA gene MT-TK encoding tRNA lysine is commonly associated with MERRF. Common mutation is A-to-G transition at nucleotide 8344. This mutation can also be associated with isolated "limb-girdle" myopathy. We describe a 35-year-old caucasian female with a history of progressive exercise intolerance and increased CK. Physical examination showed a limb girdle weakness, facial diparesis, limitation of abduction on eye movements without ptosis and arreflexia. Lung function studies showed a restrictive pulmonary syndrome. The muscle biopsy revealed numerous ragged red fibbers. An A-to-G transition at nucleotide position 8344 in tRNA lysine gene was detected in 71% of the patient´s lymphocytes. At the age of 36 she gave birth to a male child with high plasma lactate levels and normal development. After she developed symptoms of nocturnal hypoventilation and non-invasive ventilation was initiated. Six years after the initial diagnosis she needed help to get up, but walked alone and needed nocturnal non-invasive ventilation. In our patient symptoms were limited to a skeletal myopathy, "limb-girdle" distribution and respiratory involvement. Isolated mitochondrial myopathy is a rare form of presentation of the mutation tRNA Lys A8344G. Severe cases like this have been rarely described Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome is a rare multisystemic disorder with typical onset in childhood caused by mutations in mitochondrial DNA. Cases reports 1: 28-year-old man, presenting with 2 acute episodes of behavioural and speech disorder with focal deficits and parieto-temporal lesion on MRI. The diagnosis of MELAS was based on his phenotype and history of hypogonadism and hypothyroidsm. MELAS was confirmed with 3243A>G mut. 2: A low stature boy beginning with seizures at 13 years. The MRI revealed multiple "vascular" lesions (thalamic and occipital bilaterally). Over the time, seizures increased in frequency and developed other neurological signs in relation with news lesions. The diagnosis was suggested by muscle biopsy. The respiratory chain was deficient in complex I. He died at age of 21. 3: 47-year-old man, presented at 45Y with partial seizure. CT appeared an extensive pseudo-stroke. About 7 months later he developed right homonymous hemianopsia and aphasia secondary a new left occipitotemporal lesion. Myoclonic epilepsy and metabolic acidosis began. Muscular biopsies suggest MELAS. We present 3 MELAS, age at onset 13-45, with stroke-like episodes and associated seizures. The diagnosis was obtained by typical MRI, muscular biopsy and positive genetic analysis in one of them.