We describe the first Finnish case of hepatitis C associated osteosclerosis. In which the patient's bone symptoms and bone density were resolved with hepatitis C treatment. Suspecting the possibility of osteosclerosis underlying bone pains in a hepatitis C patient is well-founded, although osteoporotic fractures are a more common problem.

Multiple acyl-CoA dehydrogenation deficiency is genetically heterogenous metabolic disease with mutations in genes involved in electron transfer to the mitochondrial respiratory chain. Disease symptoms vary from severe neonatal form to late-onset presentation with metabolic acidosis, lethargy, vomiting, muscle pain and weakness. Riboflavin therapy has been shown to ameliorate diseases symptoms in some of these patients. Recently, mutations in FAD synthase have been described to cause multiple acyl-CoA dehydrogenation deficiency. We describe here the effect of riboflavin supplementation therapy in a previously reported adult patient with multiple acyl-CoA dehydrogenation deficiency having compound heterozygous gene variations in FLAD1 (MIM: 610595) encoding FAD synthase. We present thorough clinical history including laboratory investigations, muscle MRI, muscle biopsy and spiroergometric analyses comprising of a follow-up of 20 years. Our data suggest that patients with adult-onset multiple acyl-CoA dehydrogenation deficiency with FLAD1 gene mutations also benefit from long-term riboflavin therapy.

BACKGROUND:Anoctaminopathies are muscle diseases caused by recessive mutations in the ANO5 gene. The effects of anoctaminopathy on oxidative capacity have not previously been studied in a controlled setting.OBJECTIVE:To characterize oxidative capacity in a clinically and genetically well-defined series of patients with anoctaminopathy.METHODS:We sequenced the ANO5 gene in 111 Finnish patients with suspected LGMD2. Patients with positive findings underwent close clinical examination, including electromyography, muscle MRI, and, in selected cases, muscle biopsy. Oxidative capacity was analyzed using spiroergometry and compared to age-matched healthy controls.RESULTS:We characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Our material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, we found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. Lower limb muscle MRI revealed progressive fatty degeneration of specific posterior compartment muscles. Patients' spiroergometric profiles showed that anoctaminopathy significantly impaired oxidative capacity with increasing ventilation.CONCLUSIONS:Our findings support earlier reports that anoctaminopathy progresses slowly and demonstrate that the disease impairs the capacity for aerobic exercise.

Anoctaminopathy is a new muscular dystrophy caused by mutations in the ANO5 gene. ANO5 mutations cause distal and proximal phenotypes. We report here a follow-up muscle MRI study on five patients affected by distal form of anoctaminopathy. T1 weighted scans showed subsequent involvement of gastrocnemius medialis and soleus, hip adductors, hamstrings, gastrocnemius lateralis and quadriceps muscles, and later on tensor fascia lata, gluteus minimus and biceps brachii muscles, respectively. The STIR weighted images showed in the early stages widely distributed hyperintense signals, myoedema, in the adductors, hamstrings, and quadriceps muscles, which at that time have normal T1 signals. All patients showed asymmetry of muscle involvement both clinically and on muscle imaging. The progression of muscle involvement was relatively slow. We conclude that the pattern of muscle involvement seen in patients with distal myopathy with anoctamin 5 mutations (MMD3) is typical and can thus be useful during the differential diagnosis process allowing for a more targeted molecular approach.

A middle-aged male patient was examined due to chest pain. At the same time blisters appeared on his palms and soles of the foot. Radiologic examinations revealed lesions in the thoracic vertebral bodies, in the first rib and in the sternum. Inflammatory markers were elevated in the blood. The patient subsequently developed arthritis in a previously injured knee.

A previously quite healthy 65-year-old woman sought emergency hospital care due to fatigue, weight loss and sensation of thirst appearing over a couple of months. Further analysis revealed a process affecting the neurohypophysis and extensive lytic sclerotic bone lesions. Eventually a rare generalized underlying disease was unraveled: the diagnosis included both Langerhans cell histiocytosis and Erdheim-Chester disease.

BACKGROUND:Many children with permanent brachial plexus birth injury (BPBI) develop shoulder problems, with subsequent joint deformity without treatment. We assessed the indications and outcome of shoulder operations for BPBI. PATIENTS AND METHODS:31 BPBI patients who had undergone a shoulder operation in our hospital between March 2002 and December 2005 were included in the study. Relocation of the humeral head had been performed in 13 patients, external rotation osteotomy of the humerus in 5 patients, subscapular tendon lengthening in 5 patients, and teres major transposition in 8 patients. Subjective results were registered. Shoulder range of motion was measured, and function assessed according to the Mallet scale. Magnetic resonance imaging (MRI) was performed pre- and postoperatively. Glenoscapular angle (GSA) and percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) were measured. Congruency of the glenohumeral joint (GHJ) was estimated. The mean follow-up time was 3.8 (1.7-6.8) years. RESULTS:At follow-up, the subjective result was satisfactory in 30 of the 31 patients. There were 4 failures, which in retrospect were due to wrong choice of surgical method in 3 of these 4 patients. Mean increase in Mallet score was 5.5 after successful relocation, 1.4 after rotation osteotomy, 2.2 after subscapular tendon lengthening, and 3.1 after teres major transposition. Congruency of the shoulder joint improved in 10 of 13 patients who had undergone a relocation operation, with mean improvement in GSA of 33º and mean increase in PHHA of 25%. There were no substantial changes in congruency of the glenohumeral joint in patients treated with other operation types. INTERPRETATION:Restriction of the range of motion and malposition of the glenohumeral joint can be improved surgically in brachial plexus birth injury. Remodeling of the joint takes place after successful relocation of the humeral head in young patients.

We have been following clinically and with muscle MRI for the past 3-decades a Finnish family with two patients with distal muscular dystrophy. Previously we demonstrated the cellular defect in these patients to be defective membrane repair and more recently have identified the causative gene to be anoctamin 5 (ANO5). The disorder seen in these patients is characterized by onset in the third decade. First symptoms were burning sensation on the calves and later on calf tightness during running. Muscle weakness and wasting were asymmetric and early involving the calf muscles, later spread to the thigh muscles. Biceps brachi was later manifestation. Clinical course was slow. CK levels were high. Muscle biopsy showed dystrophic pattern and multifocal disruption of the sarcolemmal membrane but no subsarcolemmal vesicle accumulation nor active inflammation. We conclude that the disease seen in our cases is a new separate clinical, genetic and histopathologic entity to include within the classification of autosomal recessive distal muscular dystrophies.

INTRODUCTION:Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied.METHODS:Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 μg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing.RESULTS:Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7-fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N-telopeptide of type I collagen increased 14- to 19-fold and 9-5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7-8 months of treatment in patient 1 and at 15 months in patient 2.CONCLUSION:PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response.

The purpose of this study was to evaluate the long-term results of arthroscopic resection of a medial plica and to describe the usefulness of the clinical findings and MRI for preoperative diagnostics. From the baseline population of 172,777 military conscripts, thirty-three consecutive young adult patients with normal preoperative MRIs of the knee and a sole postoperative diagnosis of medial plica were treated with arthroscopic plica resection. Functional outcome was evaluated at a final follow-up in 25 patients with 34 knees with Kujala, Lysholm and visual analog scale (VAS) scores. Functional results were excellent to good in 17 patients, fair in three patients, and poor in 3 patients. The median Kujala score was 92 (25-100), the median Lysholm score 89 (26-100), and the median VAS 1.4 (0-8.8). Median follow-up time was 6.6 years (3.6-8.7 years). Most patients had no history of direct knee trauma preceding the symptoms. No statistically significant correlation was seen between MRI classification of the plica size or clinical findings compared to arthroscopic classification. Resection of the medial plica in a symptomatic knee has good to excellent functional long-term outcome in the majority of cases, and the procedure is not associated with postoperative complications. MRI and preoperative clinical examination seem to be unreliable in detecting medial plicae.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78- year old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin - actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.

PURPOSE:The aim of this study was to characterize the magnetic resonance imaging (MRI) findings in chronic solvent encephalopathy (CSE) patients and to study whether the findings are associated with solvent exposure indices.METHODS:The brain MRI scans of 71 CSE patients were independently re-evaluated and rated by two experienced neuroradiologists. All the work tasks were analyzed and the chemical composition of lifetime exposure was categorized.RESULTS:The MRI scans of 27/71 CSE patients (38%) were classified as abnormal. Brain atrophy in any brain area was found in 17/71 CSE patients (24%). Abnormal white matter hyperintensities (WMH) were found in 20/71 CSE patients (28%). Cerebral and cerebellar brain atrophy was associated with the duration of exposure in years, and vermian atrophy was associated with alcohol consumption. Periventricular and brainstem WMH were related to age.CONCLUSIONS:Slight brain atrophy is associated with CSE and there is a correlation between brain atrophy and the duration of exposure in years. However, all the MRI findings in CSE are non-specific and thus MRI is useful mainly in the differential diagnosis of CSE.

INTRODUCTION:Although it is known that some degenerative changes occur in the spines of fighter pilots, it is not clear whether their frequent exposure to high acceleration is associated with premature development of such changes. This case-control study was designed help answer that question.METHODS:There were 12 Finnish Air Force pilot cadets and their controls who were examined using cervical and lumbar magnetic resonance imaging (MRI) before the pilots started fighter training (baseline) and 13 yr later (follow-up) when the pilots had accumulated a total of 1200 +/- 470 h in fighter aircraft.RESULTS:No statistical differences were found between groups with respect to the frequency of degenerative changes in either the cervical or lumbar spine. Cervical changes in pilots were for the most part observed in the lower part of the neck, while controls showed more variability as to location. In the lumbar region, pilots showed a non-significant tendency toward more changes in disks L4-S1, including changes in signal intensity, height, protrusions, and end plates.CONCLUSION:Occupational exposure to acceleration in fighter aircraft did not cause significant radiological changes in the spinal column during the first 13 yr of a fighter pilot's flying career. Assessments for the need of a fighter pilot's follow-up imaging should be based on clinical outcome, not on periodic imaging.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa. and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78-year-old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 years he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin-actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.

We report a 28‐year‐old man who suffered from episodic muscle pain, stiffness and weakness. His serum creatine kinase (CK) levels were found to be elevated. He presented with slight proximal muscle weakness and calf hypertrophy. Muscle biopsy revealed fiber size variation and tubular aggregates (TA). Muscle magnetic resonance imaging showed areas of edema. Other muscle pathologies known to be associated with TAs or myoedema were ruled out.