Lysosomal storage disorders (LSDs) collectively constitute a significant public health burden in developing countries. Commoner LSDs include Gaucher, Fabry, and Niemann-Pick disease (NPD), but many cases remain undiagnosed. With the high incidence of consanguineous marriages, South East Asian countries are expected to have high prevalence of these LSDs. Here we report 4 cases of NPD type A/B in 3 families presenting with hepatosplenomegaly and cytopenias including one family with two sibs having hypertension and mitral valve prolapse. The diagnosis of NPD was proven by mutation analysis with identification of novel mutations, including a novel 4 bp insertion mutation (C>CCTGG) in exon 2 of the SMPD1 gene. We also had two cases of NPD type C, confirmed on mutation analysis.

W e evaluated a 4-day-old infant boy referred for respiratory distress and suspected congenital heart disease. He was born at 41 weeks' gestation by uncomplicated vaginal delivery and weighed 2.5 kg. His mother had been receiving oral phenytoin (300 mg daily) for the past 3 years, including the entire period of gestation, for treatment of her epilepsy. Antenatal ultrasonography at 33 weeks' gestation had shown dilated right heart with minimal pericardial effusion. The family history was not contributory. On examination, he had microcephaly, characteristic facial and acral features (Figure, AD), tachypnea, and desaturation at room air. There was no hepatomegaly or features of congestive heart failure. The remainder of the system examination was not contributory. A clinical diagnosis of fetal hydantoin syndrome secondary to in utero phenytoin exposure was considered. Investigations showed vitamin D deficiency (<3 IU/ L) with normal total and ionized calcium, parathormone, phosphorus, magnesium, coagulogram, and thyroid hormones. Sonographic examinations of cranium, spine, and urinary system, chest radiograph, and 12-lead electrocardiograph were normal. Two-dimensional echocardiography showed mild biventricular dysfunction (ejection fraction 45%-50%) with mild tricuspid regurgitation. He was supported by minimal nasal-prong oxygen and oral diuretics for a short period of time. Dysmorphic features are an important clinical clue to the diagnosis of fetal anticonvulsant syndromes. Fetal hydantoin syndrome is a spectrum of defects caused by in utero exposure to hydantoin and/or its derivatives such as phenytoin. Complete classic phenotype occurs in only 5%-10% of the cases, whereas one third of patients manifest an incomplete clinical syndrome. 1 The spectrum of abnormalities seen in the neonate includes microcephaly, distinctive facial and limb anomalies, ocular defects, growth deficiency, congenital heart defects, cardiac rhythm disturbances, and variable systemic abnormalities involving the nervous, renal, and gastrointestinal systems. Congenital heart diseases associated with fetal hydantoin syndrome include pulmonary or aortic valvular stenosis, coarctation of aorta, patent ductus arteriosus, and ventricular septal defects. 2 Our case highlights the characteristic dysmorphic features of fetal hydantoin syndrome with biventricular cardiac dysfunction in the absence of any cardiac structural or rhythm abnormalities. The pathogenesis of biventricular dysfunction could be related to transient rhythm disturbance or a direct effect on the myocardium in the absence of hypocalcemia, hypomagnesemia, or hypothyroidism in the index patient. ■

A case of Hunter syndrome, 6½-year-old boy presented with persistent thrombocytopenia and bleeding diathesis. However, cytopenia is not a usual presentation in patients with mucopolysaccharidosis II. After ruling out other causes of severe thrombocytopenia, a clinical possibility of chronic Epstein-Barr virus (EBV) infection was considered. He was treated with intravenous immunoglobulin for refractory thrombocytopenia and intracranial bleed. This was followed by oral prednisolone. The EBV serology was found positive. Platelet counts gradually recovered and no recurrence of bleeds was observed. EBV infection usually causes haematological abnormalities, mainly atypical lymphocytosis, which is a feature of infectious mononucleosis, and uncomplicated cases often present with mild decreases in platelet counts. Severe thrombocytopenia is an extremely rare complication of acute or chronic EBV infection. In Asians, EBV infection should be considered in children presenting with thrombocytopenia, bleeding diathesis and anaemia along with organomegaly.

Background. CKD patients are often asymptomatic in the early stages and referred late to nephrologists. Late referred patients carry a poor prognosis. There is a lack of data on outcomes associated with referral patterns in CKD patients from northern India. Methods. In this observational cohort study, all CKD patients who visited the nephrology OPD of the institute between Nov 1, 2018, and Dec 31, 2020, were classified as early referral (ER) if their first encounter with a nephrologist occurred more than one year before initiation of dialysis and education about dialysis (from a nurse or nephrologist). The remaining others were considered late referrals (LRs). The outcomes impact of early and late referrals was analyzed. Results. A total of 992 (male 656) CKD patients (ER, n = 475 and LR, n = 517) were enrolled. Patients referred early were older and diabetic and had higher BMI, better education, occupation, and socioeconomic status as compared to those referred late. The mean eGFR at first contact with the nephrologist was (25.4 ± 11.5 ml/min) in ER and 9.6 ± 5.7 ml/min in the LR group and had a higher comorbidity score. The CKD-MBD parameters, hemoglobin, and nutritional parameters were worse in LR. Only a few patients had AVF, and the majority required emergency dialysis in the LR group. A total of 91 (9.2%) patients died, 17 (1.7% ER and 74 (7.5%) patients in the LR group patients. There was significantly lower survival at 6 months (ER 97.1% vs. LR 89.7%), 12 months (ER 96.4% vs. LR 85.7%), 18 months (ER 96.4% vs. LR 85.7%), and 24 months (ER 96.4% vs. LR 85.7%) in late referral group as compared to early referral group P = 0.005 . Conclusions. LR to nephrologists has the risk of the emergency start of dialysis with temporary vascular access and had a higher risk of mortality. The timely referral to the nephrologist in the predialysis stage is associated with better survival and reduced mortality.

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