Search

This study aimed to assess the neurocognitive outcomes and their diffusion tensor imaging correlates in children (aged 6-16 years) with mild traumatic brain injury. This prospective analysis included 74 children with mild traumatic brain injury (52 boys; mean age: 9.5 [±2.7] years). Wechsler Intelligence Scale for Children–Indian adaptation (WISC-IV), Child Behavior Checklist, and Children's Sleep Habits Questionnaire were administered for 57 cases (at 3 months postinjury) and 51 controls of similar age. The findings of diffusion tensor imaging (done within 7 days of injury) were correlated with various WISC-IV indices. The presenting features at the time of injury were loss of consciousness (53%), confusion or disorientation (47%), and post-traumatic amnesia (10%). Other features in the acute phase included drowsiness (86%), headache (78%), balance problems (62%), nausea (47%), fatigue (45%), vomiting (35%), nasal or ear bleed (12%), sensitivity to sound and light (12%), etc. At 3 months postinjury, the children with mild traumatic brain injury performed poorly in terms of Intelligence Quotient, perceptual reasoning index, and processing speed index as compared to controls. Based on the Child Behavior Checklist, 17% of children with mild traumatic brain injury had internalizing behavioral problems in comparison with 4% of controls. Prevalence of poor sleepers in the mild traumatic brain injury cohort and controls was 12.3% and 2% respectively. Headache, reduced attention span, and fatigue were common postconcussion symptoms. There was a positive correlation between right uncinate fasciculus fractional anisotropy and verbal comprehension index (r = 0.32; P <.05). [ABSTRACT FROM AUTHOR]

Traumatic brain injury is an important cause of acquired brain injury. The current study brings to light the clinicoepidemiologic profile of pediatric traumatic brain injury in India. Retrospective record analysis of children (aged ≤ 16 years) with traumatic brain injury presenting to an apex-trauma-center in North India over 4 years was done. Of more than 15 000 patients with a suspected head injury, 4833 were children ≤16 years old. Of these, 1074 were admitted to the inpatient department; 65% were boys with a mean age at presentation being 6.6 years. Most patients (85%) had a Glasgow Coma Scale score of 13 to 15 at presentation while Glasgow Coma Scale scores of ≤8 was seen in 10% of patients. Neuroimaging (computed tomography [CT]) abnormalities were seen in 12% of patients, with the commonest abnormality being skull fracture, followed by contusions, and extradural hemorrhage. Around 2% of patients required decompressive craniotomy whereas 3% of patients succumbed to their illness. Among the inpatients with pediatric traumatic brain injury, two-thirds were boys with a mean age at presentation of 7.6 years. Severity of traumatic brain injury varied as mild (64%), moderate (11%), and severe (25%). The most common mode of injury was accidental falls (59%) followed by road traffic and rail accidents (34%). Neuroimaging abnormalities were seen in half of inpatients with pediatric traumatic brain injury, with the commonest abnormality being skull fracture. Pediatric head injuries are an important public health problem and constitute a third of all head injuries. They are more common in boys, and the most common modes of injury are accidental falls, followed by road traffic accidents. [ABSTRACT FROM AUTHOR]

The gold standard diagnostic test for Ullrich congenital muscular dystrophy (UCMD) is molecular testing for COL6 mutation. The facility for genetic testing is sparingly available and it is usually diagnosed by muscle biopsy. The latter is an invasive procedure requiring expertise and sedation. Skin biopsy has shown promise as a simpler diagnostic modality. Eleven and 7 cases, respectively, of phenotypically suspected Ullrich congenital muscular dystrophy and dystrophinopathy underwent simultaneous skin and muscle biopsies, which were subjected to hematoxylin and eosin (H&E) and immunohistochemistry staining for collagen VI and dystrophin 1, 2, and 3. Of the 8 and 5 muscle biopsy–confirmed cases of Ullrich congenital muscular dystrophy and dystrophinopathy, 6 Ullrich congenital muscular dystrophy and 5 dystrophinopathy cases showed absent and preserved COL6 staining, respectively, in the skin biopsy. Skin biopsy as a diagnostic option has shown encouraging results in Ullrich congenital muscular dystrophy. These should be evaluated in larger studies. [ABSTRACT FROM AUTHOR]

This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range = 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P = .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P = .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management. [ABSTRACT FROM AUTHOR]

There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome. [ABSTRACT FROM PUBLISHER]

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is characterized by acute- or subacute-onset encephalopathy with extrapyramidal, psychiatric, and epileptic manifestations. Diagnosis is confirmed by positive antibodies to NMDA receptor in cerebrospinal fluid and serum. Eleven pediatric cases presented over a 2-year period at a tertiary care teaching hospital in North India. The average age at presentation was 9 years (range: 2.5 to 18 years, median: 10 years) with a slight female predominance (1.2:1). The common modes of presentation were progressive extrapyramidal syndrome with global neuroregression in 45% (5 of 11), epileptiform encephalopathy in 27% (3 of 11), and an overlap between the 2 in 27% (3 of 11). Fifty-eight percent showed significant response to steroids and intravenous immunoglobulin. This entity should be considered in an acute- or subacute-onset encephalopathy if common infectious etiologies are ruled out and there are specific clinical pointers. Early diagnosis and treatment significantly improves the outcome. [ABSTRACT FROM PUBLISHER]

The study was designed to compare the Full Outline of UnResponsiveness score with Glasgow Coma Scale as a predictor of mortality and poor functional outcome at hospital discharge in children with nontraumatic impairment of consciousness. Seventy children aged 5 to 18 years admitted with impaired consciousness were enrolled. The scores were applied by the Pediatric Neurology fellow within 2 hours of admission. The primary outcome studied was in-hospital mortality. Receiver operating characteristic curves were used to compare the 2 scores. The area under the curves for Glasgow Coma Scale and Full Outline of UnResponsiveness scores were 0.916 and 0.940, respectively. However, the difference between the areas under curve for the 2 scores was not statistically significant (0.023; 95% confidence interval: –0.0115 to 0.058). Our data indicate that both the scores are good predictors for in-hospital mortality and functional outcome. However, no significant difference was observed between the ability of the 2 scores to predict the outcomes. [ABSTRACT FROM AUTHOR]

The prevalence and the burden of vincristine-induced neuropathy have been poorly documented in childhood acute lymphoblastic leukemia survivors. This cross-sectional study was carried out at a tertiary care center in northern India from October 2011 to June 2012. Eighty consecutive acute lymphoblastic leukemia survivors aged 5 to 18 years, within 3 years of completion of their chemotherapy, were enrolled. After clinical evaluation, detailed nerve conduction studies were performed and the reduced version of the Total Neuropathy Score was calculated. The mean age at the time of evaluation was 11.2 ± 3.2 years. 33.75% had neuropathy electrophysiologically. Symmetric motor axonal polyneuropathy was the most common pattern of involvement seen in 19 (23.8%) children. There was significant improvement with time, as revealed by lower prevalence of neuropathy with increasing interval following vincristine injection. 33.75% of the children had Reduced version of Total Neuropathy Score ≥ 1. [ABSTRACT FROM AUTHOR]

Encephalocraniocutaneous lipomatosis is a rare neurocutaneous syndrome characterized by classical cutaneous and ocular lesions with central nervous system anomalies. We describe an infant with classical encephalocraniocutaneous lipomatosis characterized by probable naevus psiloliparus, frontal subcutaneous lipomas, ocular limbal dermoids and arachnoid cysts, and ventriculomegaly. He also had giant congenital nevus with leptomeningeal melanosis. This case represents a rare association between encephalocraniocutaneous lipomatosis and neurocutaneous melanosis. [ABSTRACT FROM AUTHOR]

Dystrophinopathies are diagnosed by genetic studies and muscle biopsy. Most centers have multiplex polymerase chain reaction facilities diagnosing 65% to 70% of dystrophinopathy cases. Muscle biopsy is a time-consuming, invasive procedure whereas skin biopsy is a simple procedure done under local anesthesia. The current study evaluated the diagnostic accuracy of skin biopsy in dystrophinopathy. Overall, 119 confirmed cases of muscular dystrophy (111 males and 8 females) were included in the final analysis, of which 100 (all males) were dystrophinopathy. Skin biopsy diagnosed dystrophinopathy in suspected muscular dystrophy patients with a sensitivity of 98% (92.3%-99.7%), specificity of 99% (93.7%-99.9%), positive predictive value of 94.7% (71.9%-99.7%), and negative predictive value of 90% (66.9%-98.2%). Skin biopsy can be used for screening dystrophinopathy in muscular dystrophy patients (high sensitivity and positive predictive value). It being a simple and minimally invasive procedure, histopathologic and molecular markers of disease progression and response to novel treatment options can be assessed serially. [ABSTRACT FROM PUBLISHER]

The present study was designed as a 12-week, randomized, double-blind, placebo-controlled pilot study to evaluate the effectiveness and safety of donepezil in boys with fragile X syndrome. Twenty boys with fragile X syndrome were randomized to receive 12 weeks of treatment with either placebo or donepezil (2.5 mg daily for initial 4 weeks followed by 5 mg daily for next 8 weeks). The outcome measures included change in intelligence quotient scores on Stanford-Binet Intelligence Scale (Hindi adaptation by Kulshrestha), change in behavioral scores by Conners 3 Parent Rating Scale (Short) and Childhood Autism Rating Scale, safety, and tolerability of donepezil. The study failed to show significant difference in intelligence quotient and behavioral scales with donepezil therapy over 12 weeks. However, donepezil appeared to be safe and well tolerated. [ABSTRACT FROM AUTHOR]

Harlequin syndrome, Harlequin sign, Holmes-Adie syndrome, and Ross syndrome lie on a spectrum of partial dysautonomias affecting facial sudomotor, vasomotor, and pupillary responses. These syndromes have imprecise clinical boundaries and overlap syndromes are known. We report a 9-year-old girl who presented with anhidrosis over the right half of her face and the left side of her body, with compensatory hyperhidrosis on the contralateral side. She was noted to have bilateral tonic pupils and normal muscle stretch reflexes with other features suggestive of autonomic dysfunction. Investigations to rule out secondary causes were noncontributory. Her clinical presentation can be categorized as partial overlap between Harlequin syndrome and Holmes-Adie syndrome. [ABSTRACT FROM AUTHOR]

A 3-year-old girl who presented with anemia, thrombocytopenia, and recurrent strokes is described. The cerebral angiography revealed moyamoya vasculopathy. Her younger brother also had anemia and thrombocytopenia but no neurologic abnormalities. Both children had severe deficiency of ADAMTS13 (A Disintegrin And Metalloprotease with Thrombospondin like domain activity) confirming the diagnosis of congenital thrombotic thrombocytopenic purpura. The children responded well to regular fresh-frozen plasma infusions. This report expands the spectrum of hematologic diseases associated with moyamoya syndrome. Unexplained thrombocytopenia, especially in the presence of neurologic symptoms, should prompt an evaluation for ADAMTS13deficiency. The diagnosis has significant implications not only for therapy but also for genetic counseling. [ABSTRACT FROM PUBLISHER]

There are conflicting reports in the literature about the influence of valproate on thyroid function. A cross-sectional study was performed to determine the prevalence of subclinical hypothyroidism in ambulatory children aged 3 to 15 years with controlled epilepsy receiving valproate monotherapy for at least 6 months. Fifty-seven consecutive children with controlled epilepsy on valproate monotherapy and 52 healthy age- and sex-matched control children were studied. Thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, and serum valproic acid levels were measured. There was a significantly high (P = .012) prevalence of subclinical hypothyroidism (26%) in those receiving valproate monotherapy compared with healthy controls (7.7%). Median duration of valproate therapy was significantly higher (P = .039) in the subclinical hypothyroidism group (21 months, range 6-36) compared with those without subclinical hypothyroidism (14 months, range 6-25). Results of the present study suggest higher prevalence of subclinical hypothyroidism in children with controlled epilepsy on long-term valproate monotherapy. [ABSTRACT FROM PUBLISHER]

A 10-year-old girl presented with progressive proximal limb muscle weakness without facial, ocular, or bulbar muscle involvement. There was no fatigability or diurnal fluctuation in symptoms. Her weakness worsened with febrile illnesses and recovered with accruing disabilities over a few weeks. Serum creatine kinase levels and muscle biopsy were normal. A significant decrement on repetitive nerve stimulation test and positive response to therapeutic neostigmine challenge test confirmed the diagnosis of limb-girdle myasthenia. She responded well to corticosteroids and thymectomy, demonstrating a likely autoimmune etiology. This case highlights the long-term fluctuations in a case of myasthenia gravis and the need for a high index of suspicion for myasthenia in children presenting with unexplained muscle weakness, even in the absence of typical features such as fatigability, diurnal fluctuation, and oculobulbar weakness. [ABSTRACT FROM PUBLISHER]

A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy. Interestingly, magnetic resonance spectroscopy of the abnormal white matter did not reveal elevated lactate. The patient was compound heterozygous for 2 new mutations in DARS2, genetically confirming the diagnosis. [ABSTRACT FROM PUBLISHER]

Mutations in MECP2 gene are the primary cause of Rett syndrome, a neurodevelopmental disorder that primarily affects girls, and affect 90% to 95% patients with classical Rett syndrome. MECP2 mutations, once thought to be lethal in males, now present a broad spectrum of clinical manifestations in males. This article reports a family with a 9-year-old boy with Rett-like phenotype and congenital blindness, who inherited a novel MECP2 variant (p.P430S) from his asymptomatic mother. The variant was also identified in the asymptomatic maternal grandfather and maternal aunts of the proband, ruling out the possibility that the p.P430S was involved in the phenotype. Findings of the study suggest that a careful evaluation of the pathogenic nature of MECP2 variants identified in males be conducted before proposing genetic counseling or prenatal diagnosis to the family and that the interference of other factors like modifier genes, environment, epigenetics, and mosaicism be taken into account. [ABSTRACT FROM AUTHOR]

This cross-sectional study was planned to study the blood ammonia levels in epileptic children on 2 dose ranges of valproic acid monotherapy. A total of 60 epileptic children aged 3 months to 12 years, that were on valproic acid monotherapy for at least 3 months, were enrolled and divided into 2 groups, a low-dose group (dose, 20-39 mg/kg/d [n = 32]) and a high-dose group (dose, 40-60 mg/kg/d [n=31]). Measurements of blood ammonia, serum valproic acid levels, and liver and renal function tests were performed. Blood ammonia levels were significantly higher in the high-dose group (median, 79.2 µg/dL; range, 55.23-114.29 µg/dL) as compared with the low-dose group (median, 47.2 µg/dL; range, 20.62-73.25 µg/dL). Blood ammonia levels significantly correlated with both the dose (r = .77, P < .001) and serum levels (r = .88, P < .001) of valproic acid. All the children with hyperammonemia were asymptomatic. There were no significant differences in the other biochemical parameters between the 2 groups. [ABSTRACT FROM AUTHOR]

A 10-year-old boy with tuberous sclerosis complex and macrodactyly of the right index and middle fingers is described. He also had a fibrous hamartoma at the front of the right wrist. The association of fibrous hamartoma and macrodactyly has not been previously described in tuberous sclerosis complex. [ABSTRACT FROM AUTHOR]

X-linked adrenoleukodystrophy is an inherited neurological disorder caused by mutations in the ABCD1 gene (located on chromosome Xq28) encoding adrenoleukodystrophy protein which is involved in the transport of substrates from the cytoplasm into the peroxisomal lumen. There is a scarcity of reports onmutation analysis of X-linked adrenoleukodystrophy from India. Here, we report 3 novel variants (c.67>83del17, c.395G>A, c.1938_1939dupGG) in 3 unrelated Indian families. [ABSTRACT FROM AUTHOR]

Intractable epilepsies pose a therapeutic challenge. Precise localization of the epileptic focus is imperative before planning surgical intervention. Functional imaging is an important component of presurgical work-up. Positron emission topography is unavailable in developing countries; hence, the need to evaluate the available imaging modality, single photon emission computed topography (SPECT), was felt. We investigated 61 children with intractable epilepsy, identified by predefined criteria, by performing electroencephalography (EEG), magnetic resonance imaging (MRI), computed topography (CT), and ictal and interictal SPECT. The localizing value of ictal and interictal SPECT imaging for epileptic foci was correlated with clinical, electrophysiologic, and anatomic neuroimaging data. An ictal SPECT was obtained in 9, and interictal SPECT was performed in all (61). Ictal SPECT was localizing in 8 of 9 (88.8%). Interictal SPECT was localizing in a significantly higher proportion of patients (47.54%) than either the scalp EEG (16.39%) (P = .0003) or CT scan (21.56%) (P = .0046). Our data demonstrated that interictal and ictal SPECT identified more focal changes in children with intractable epilepsy than interictal EEG, CT, and probably MRI. The definitive proof of the SPECT-based findings being epileptogenic foci awaits correlation with intraoperative monitoring and postoperative follow-up. (J Child Neurol 2001;16:257–263). [ABSTRACT FROM AUTHOR]

Various micronutrients are essential for optimal functioning of the peripheral nervous system. Serum vitamin E, vitamin B12, and folic acid were estimated in childhood acute lymphoblastic leukemia survivors aged between 5 and 18 years in first continuous remission within 3 years of completion of vincristine-based chemotherapy with and without electrophysiologically defined neuropathy. A total of 80 children were studied. Neuropathy was seen in 27 (33.75%) children electrophysiologically. None of the children had vitamin E deficiency. However, the alpha tocopherol/(cholesterol + triglyceride) ratio was significantly lower in children with neuropathy (P = .05). The prevalence of folate (P = .48) and vitamin B12 (P = .21) deficiency in children with and without neuropathy was not significantly different. Thus, the prevalence of deficiencies of these micronutrients was not significantly different in childhood acute lymphoblastic leukemia survivors with or without electrophysiologically defined neuropathy. [ABSTRACT FROM PUBLISHER]

Alexander disease is an autosomal dominant leukoencephalopathy characterized by developmental delay, macrocephaly, and characteristic neuroimaging abnormalities predominantly involving frontal lobes. We report a 6-year-old Indian boy with infantile-onset Alexander disease, who has an unusually mild clinical course and a de novo p.Leu359Val mutation in the glial fibrillary acidic protein gene. [ABSTRACT FROM AUTHOR]

Spontaneous spinal epidural hematoma is a rare entity, especially in infants. The cervicothoracic region is the most commonly affected site in children. The clinical features are often nonspecific, leading to a delay in diagnosis. Early management is probably associated with better functional outcomes. Here the authors report a 12-month-old girl who presented with excessive irritability and weakness of limbs. Magnetic resonance imaging of spine revealed epidural hematoma on the dorsal aspect of the spinal cord in the C2–C5 region. There were no predisposing factors. She started showing neurological recovery even prior to presentation. She was managed conservatively. This case report aims to raise awareness about this otherwise morbid neurological emergency, in which early intervention is pivotal. [ABSTRACT FROM AUTHOR]

A 5-year-old boy who presented with progressive ataxia, neuroregression, and worsening with febrile illnesses is described. He also had myoclonic jerks and ptosis. His elder sister had died of a similar illness. Serial magnetic resonance imaging of the brain demonstrated extensive abnormality of the cerebral white matter with rarefaction and cystic degeneration, suggestive of vanishing white matter disease. The patient was found to be compound heterozygous for 2 new mutations in the gene EIF2B5, confirming the diagnosis. [ABSTRACT FROM AUTHOR]

Poliomyelitis, though eradicated from most parts of the world, continues to occur in India. There is paucity of data on the magnetic resonance imaging (MRI) changes in poliomyelitis. We report a 3½-year-old boy who presented with subacute onset flaccid paralysis and altered sensorium. Stool culture was positive for wild polio virus type 3. Magnetic resonance imaging revealed signal changes in bilateral substantia nigra and anterior horns of the spinal cord. These MRI changes may be of potential diagnostic significance in a child with poliomyelitis. [ABSTRACT FROM AUTHOR]

We report the case of a 7-month-old child who presented with regression of milestones, seizures, altered sensorium, and vomiting. An elder sibling had died of similar complaints. Lead encephalopathy was considered because of presence of microcytic hypochromic anemia and dense metaphyseal bands on wrist radiogram. Magnetic resonance imaging (MRI) of the brain revealed diffuse dysmyelination involving both periventricular and subcortical white matter. Such diffuse changes have not been described previously. The child's father was operating an illicit lead-acid battery manufacturing unit at home. The child was subjected to chelation therapy, which was accompanied by environmental exposure source modification. He showed significant improvement. Our case highlights the importance of taking a detailed occupational history and considering lead poisoning in the differential diagnosis of encephalopathy of unidentifiable cause. [ABSTRACT FROM AUTHOR]

The article presents a case study of a three-year-old boy who was suffering with a head trauma after getting hit by a car. It states that a minimal hemorrhage was shown in the initial noncontrast computed tomography scan of the brain and signal change in pons with peripheral sparing was shown in magnetic resonance images. It mentions the initiation of the rehabilitative physiotherapy and supportive care.

A 12-year-old boy presented with complaints of seizures since the age of 7 years. Seizure semiology was consistent with origin from the right temporal lobe. Magnetic resonance imaging of the brain revealed a large right temporal and multiple small intracranial cavernomatous hemangiomas. The imaging findings and clinical significance of cavernomatous hemangiomas are briefly discussed. [ABSTRACT FROM PUBLISHER]

Deficiency of vitamin B12 causes megaloblastic anemia and nervous system demyelination. Structures affected in the nervous system include spinal cord, cranial and peripheral nerves, and brain white matter. A 9-year-old boy presented with knuckle hyperpigmentation and oral ulcers for 3 years, pallor and easy fatigability for 6 months, gait abnormalities for 3 months, and abnormal speech and behavioral abnormalities for 3 days. On examination, he had physical signs of megaloblastic anemia, mood swings with intermittent hallucinations, and features of cerebellar impairment. Blood investigations revealed megaloblastic anemia, and pernicious anemia was ruled out. Brain magnetic resonance imaging (MRI) revealed bilateral cerebellar signal changes. He received treatment for vitamin B12 deficiency and appropriate nutritional counseling. Three months later, he showed significant clinical and radiologic resolution. To our knowledge, isolated cerebellar involvement as the sole neurologic manifestation of vitamin B12 deficiency has not been described previously in children. [ABSTRACT FROM PUBLISHER]

Muscular dystrophies are progressive, genetic disorders of muscle degeneration. The current gold standard for diagnosis is muscle biopsy or genetic studies. Muscle biopsy is an invasive procedure and genetic testing facilities are available only in a few centers. Thus, a diagnostic test that is easily available, simpler, and less invasive is desirable. Over the past 2 decades, skin biopsy has been evolving as a suitable option. Two cases of sarcoglycanopathy are described here, which have been correctly diagnosed by skin biopsy. Muscle biopsy has been used as the gold-standard diagnostic method. Skin biopsy can substitute for muscle biopsy as the preliminary diagnostic tool directing appropriate molecular testing. However, these results require validation in studies with an adequate sample size. This holds promise for the future when repeated biopsies will be required for evaluating protein rescue in trials of novel treatment options in these disorders. [ABSTRACT FROM AUTHOR]