Autosomal Recessive Myotonia Congenita in an Adolescent Boy With Novel Mutation: A Case Report With Discussion on Management.

Congenital myotonia represents a rare group of genetically inherited conditions. It can be either autosomal dominant (Thomsen) or autosomal recessive (Becker). It is characterized by muscular hypertrophy, proximal weakness, and myotonia, or impaired relaxation after contraction. These are due to mutations in the CLC1 gene. A 14-year-old male child presented with complaints of gradually progressive weakness for five years. Weakness was more pronounced in the proximal muscle groups. The weakness worsened after rest and improved with activity. This led to absenteeism and affected his school performance. Clinical examination showed generalized muscular hypertrophy with pronounced hypertrophy of the calf muscles. A neurological examination showed significant myotonia and impaired relaxation after making a fist. The diagnosis of myotonia was confirmed by electromyography, which produced a dive-bomber sound on insertion. Next-generation sequencing revealed a homozygous eight-base pair insertion in exon 19 of the CLCN1 gene. This mutation has not been reported in the existing literature for myotonia congenita. The child was started on mexiletine and improved significantly. Presently, the patient is on regular medications and doing well on follow-up. Though rare, congenital myotonia is an important cause of neuromuscular weakness. It can be easily diagnosed with a thorough clinical examination and routine testing for myotonia in all children with weakness. The treatment is relatively simple and can give the patient significant relief. Myotonia can be easily diagnosed clinically, and pharmacotherapy and proper monitoring can remarkably improve patients' quality of life.

Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children.

Background: Hypermanganesemia with dystonia 1 and 2 (HMNDYT1 and 2) are rare, inherited disorders of manganese transport. Objectives: We aimed to describe clinical, laboratory features, and outcomes among children with HMNDYT. Methods: We conducted a retrospective multicenter study involving tertiary centers across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/clinically probable HMNDYT. Clinical, laboratory profile, genetic testing, treatment details, and outcomes scored by treating physicians on a Likert scale were recorded. Results: We enrolled 27 children (19 girls). Fourteen harbored SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus SLC30A10 cohort (2.0 [IQR, 1.5-5.1] years). The most frequent neurological features were dystonia (100%; n = 27), gait abnormality (77.7%; n = 21), falls (66.7%; n = 18), and parkinsonism (59.3%; n = 16). Median serum manganese (Mn) levels among SLC39A14 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than SLC30A10 (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in SLC30A10 (16.3 [IQR, 15.2-17.5] g/dL) versus SLC39A14 cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in SLC30A10 variants. A total of 26/27 children underwent chelation with disodium calcium edetate. Nine demonstrated some improvement, three stabilized, two had marked improvement, and one had normalization. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up. Conclusions: We found female predominance. Children with SLC39A14 mutations presented at younger age and responded less favorably to chelation compared to SLC30A10 mutations. There is emerging need to better define management strategies, especially in low resource settings.

An interesting case of metabolic dystonia: L-2 hydroxyglutaric aciduria.

L-2-hydroxyglutaric aciduria (L-2-HGA), a neurometabolic disorder caused by mutations in the L-2 hydroxyglutarate dehydrogenase (L-2-HGDH) gene, presents with psychomotor retardation, cerebellar ataxia, extrapyramidal symptoms, macrocephaly and seizures. Characteristic magnetic resonance imaging findings include subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus, putamen and caudate nucleus. The diagnosis can be confirmed by elevated urinary L-2 hydroxyglutaric acid and mutational analysis of the L-2-HGDH gene. We report two siblings with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid. Riboflavin therapy has shown promising results in a subset of cases, thus highlighting the importance of making the diagnosis in these patients.

Biotinidase deficiency in childhood.

This study reports the clinical, laboratory profile and outcome in seven patients with biotinidase deficiency. The serum biotinidase activity was assayed using spectrophotometric analysis. The age at presentation varied from day 1 of life to the 5 th month. Seizures were the presenting complaint in six patients and clonic seizures were the predominant seizure type. Sparse hair was seen in four patients, while three did not have any cutaneous manifestation. None of the patients had acidosis or hyperammonemia. The clinical response to biotin was dramatic with seizure control in all patients. One patient had neurological deficit at follow-up, while none had optic atrophy or sensorineural hearing loss. Biotinidase deficiency, a potentially treatable condition, should be thought of in any child presenting with neurological symptoms, especially seizures, even in the absence of cutaneous or laboratory manifestations.