Nearly a thousand mutations mapping to 60 different loci have been identified in cerebellar ataxias. However, almost 50% of the cases remain genetically uncharacterized and there is a difference in prevalence as well as in the phenotypic spectrum of ataxia among various geographical regions. This poses a challenge for setting up a genetic panel for screening ataxia. In our ataxic cohort of 1014 families, 61% are genetically uncharacterized (UC). We investigated the potential of whole exome sequencing in conjunction with homozygosity mapping (HM) to delineate the genetic defects in three uncharacterized families with recessive inheritance each manifesting some unusual phenotype: (i) infantile onset ataxia with hearing loss (IOAH), (ii) Juvenile onset cerebellar ataxia with seizures (JCS) and (iii) Friedreich ataxia-like (FA-like). We identified a novel missense mutation in c10orf2 in the family with IOAH, compound heterozygous mutations in CLN6 in the family with JCS and a homozygous frame-shift mutation in SACS in the FA-like patient. Phenotypes observed in our families were concordant with reported phenotypes of known mutations in the same genes thus obviating the need for functional validation. Our study revealed novel variations in three genes, c10orf2, CLN6, and SACS, that have so far not been reported in India. This study also demonstrates the utility of whole exome screening in clinics for early diagnosis.

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Lead poisoning, fairly common in the 20th century, has decreased drastically in the last decade. Severe lead poisoning in the form of encephalopathy has a fatality rate of 28% to 45% and neurological sequelae in about 82%. We present the management of a case of lead encephalopathy that recovered without any significant neurological sequelae in a resource-limited setting. A previously healthy seven-year-old boy presented with complaints of falling unconscious on the ground while playing, followed by multiple episodes of seizures, vomiting, and altered sensorium. The patient had pallor, Glasgow coma score of E2V3M3, with features of raised intracranial pressure. Lead poisoning was suspected as the patient had four months of exposure to a battery recycling factory. Management of seizures and raised intracranial pressure was done. X-ray long bones showed lead lines at the metaphysis. Blood lead levels were highly elevated (139.96 mcg/dL). Investigations revealed iron deficiency anemia, vitamin D deficiency, and renal tubular injury in the form of proteinuria. D-penicillamine with supplements was started due to unavailability of other chelating agents. Encephalopathy improved, but patient had psychiatric symptoms of hallucinations and delusions. On the 12th day, CaNa 2 EDTA was started, which resulted in significant improvement in the psychiatric symptoms.The patient had near-complete recovery in another one month, the patient being able to read, write, recite and speak as the pre-illness state. In conclusion, lead poisoning remains a significant health problem even today. Early recognition and management are of paramount importance in its outcome.

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BackgroundPlasma interleukin-33 (IL-33), a cytokine associated with inflammatory and autoimmune disease, has been described to be significantly raised in osteonecrosis of the femoral head (ONFH) and hence was recommended for use as a marker for ONFH. The concentration of plasma interleukin-33 level has not been estimated in any studies conducted in patients with sickle cell disease (SCD); hence, we investigated the levels of plasma interleukin-33 in patients with sickle cell disease with or without ONFH to assess whether it can be used as a marker for the early detection of ONFH in this disease also. MethodsForty-four consecutive patients with sickle cell disease with osteonecrosis of the femoral head and matched controls without ONFH were evaluated for plasma interleukin-33 levels by enzyme-linked immunosorbent assay (ELISA). All patients were confirmed for sickle cell disease using high-performance liquid chromatography (HPLC). ONFH was diagnosed in patients with sickle cell disease using clinical-radiological findings. Univariate and multivariate analyses were performed using the IL-33 level as the dependent variable. ResultsPlasma IL-33 levels were comparable in 44 patients with sickle cell disease with osteonecrosis of the femoral head as compared with 24 patients with sickle cell disease without ONFH (2.05 ± 4.57 pg/mL versus 1.50 ± 2.89 pg/mL, p-value = 0.590). There was no significant difference in IL-33 levels in different stages of avascular necrosis (AVN). ConclusionsPlasma interleukin-33 levels cannot act as a marker of ONFH as were being considered in idiopathic ONFH or ONFH caused by other causes such as trauma and chronic steroid or alcohol usage.