The patients were the children of healthy, unrelated parents, born at term by normal delivery after a normal pregnancy. The definite diagnosis was made by sequence analysis of the AHCY gene which revealed two mutations: the maternally derived c.336G>A (p.W112X) and the paternally derived c.428A>G (p.Y143C).
All three brothers had similar symptoms: psychomotor delay, myopathy, mild hepatopathy with disturbed coagulation, behavioral problems, and cognitive impairment. Myopathy was the most prominent symptom, and unamenable to treatment. At the time of skeletal muscle MRI and MRS, all patients had hypotonia and muscle weakness, more prominent in the proximal muscle groups especially in the lower extremities, fatigability and obesity due to low physical activity, but all walked unassisted, and were able to perform everyday chores.
CASE 1 
Index patient had delayed psychomotor development since birth. He presented at the age of eight months with severe developmental delay, hypotonia, more in lower than upper extremities, convergent strabismus and microcephaly. Diagnostic work-up showed increased activities of CK and aminotransferases, low albumin and prolonged prothrombin time (the later as signs of impaired liver synthetic function). Electromyography showed myopathic potentials. Histopathological examination of skeletal muscle revealed variability in fiber size with few necrotizing fibers undergoing phagocytosis and some basophilic regenerating fibers, histochemistry demonstrated no specific pathological changes, whereas electron microscopy showed numerous myelin figures of different sizes and shapes in muscle fibers and extracellularly and numerous enlarged and abnormally shaped mitochondria within some fibers. In the liver tissue there were signs of mildly active chronic hepatitis. Brain MRI revealed white matter atrophy and impaired myelination. The diagnosis of SAHH deficiency was confirmed at the age of 12.8 months by measuring low SAHH activity in red blood cells, fibroblasts and liver, and confirming two pathogenic mutations in the AHCY gene. Methionine-restricted diet and supplementation of phosphatdylcoline and creatine were started at the age of 13 months. Treatment resulted in marked decrease of biochemical biomarkers of this disorder (AdoMet, AdoHcy and methionine), and gradual, but constant, clinical improvement. Patient became more alert, communicative, and muscle strength improved. He started to walk unassisted at age 19 months. Control brain MRI, after seven months of treatment, showed near normal myelinization for age . Elevated CK and aminotransferases remained despite the treatment. Second muscle biopsy was obtained at 12.5 years and showed fiber variability, endomysial oedema, with some fatty infiltration and inflammation. Histochemistry and immunohistochemistry demonstrated no significant changes, and electron microscopy showed normal-sized and shaped mitochondria with swollen cristae and subsarcolemmal myelin figures . At the time of skeletal muscle MRI and MRS patient was 13 years old.
CASE 2 
Patient was hypotonic since birth. At first clinical evaluation at 15 days of life he had reduced spontaneous movements, generalized hypotonia and absent tendon reflexes. As his older brother, he had elevated CK and aminotransferases, and delayed myelination and frontotemporal atrophy on brain MRI. In contrast to his brother, patient had neither manifesting liver disease nor coagulation disturbance. The diagnosis of SAHH deficiency had been clearly established at the age of 3.4 months (elevated AdoMet and AdoHcy, very reduced activity of SAHH in red blood cells, and confirmation of two biallelic family mutations in the ACHY gene) At the time of diagnosis, the boy had hypotonia, convergent strabismus, and developmental delay, althoughless severe than his older brother at corresponding age. At that time, treatment was started (low methionine diet with phosphatidylcholine and creatine supplementation), which resulted in improved strength, alertness and spontaneous movements. In subsequent period strabismus disappeared, tendon reflexes, although week, could be elicited and muscle hypotonia was less evident. CK and aminotransferases remained permanently elevated. Patient was able to sit unsupported at 10 months, and to stand and walk with support at 13 months. Control brain MRI performed seven months after the treatment initiation showed almost normal myelination for age. The biopsy of the right deltoid muscle was done at age 13.5 months and histological examination revealed fairly normal muscle fibers except for slightly increased variation in fiber size. Immunohistochemically, expressions of dystrophin, merosin and alpha-sarcoglycan were normal. Electron microscopy revealed a small number of myelin figures with different sizes and shapes, and focal myofibrillar degeneration in the subsarcolemmal regions of an occasional muscle fiber . Long term follow-up showed that patient 2 had the best outcome considering muscle strength and endurance (he was able to play football with his peers), but cognitive abilities as well. He was 11 years old at the time of MRI and MRS
CASE 3 
Third patient, whoharboured the same pathogenic mutations of the AHCY gene, exhibited clear signs of myopathy since birth: sluggishness, shallow breathing, floppiness, diminished spontaneous activity and absent tendon reflexes. Comparison to his brothers regarding presentation of their inherited disease was somewhat complicated, as this patient experienced mild perinatal hypoxia (Apgar score 8/9) which might had contributed to the clinical symptoms. He also had elevated AdoMet. AdoHcy, and CK. Low methionine diet and oral phosphatidylcholine supplementation were started at age 18 days, and creatine was added a month later. On treatment patient gradually gained strength, became more alert with better contact and spontaneous activity. Patient had permanently elevated CK and delayed milestones (unsupported walking at 19 months of age). A muscle sample was taken during orthopedic procedure of the hip at the age of 4.4 years and histopathology, immunohistochemistry, and electron microscopy showed normal finding . This patient was 8 years old at the time of MRI and MRS.