Transient hyperphosphatasemia in a toddler with COVID-19 infection: A case report and literature review.

BACKGROUND: Transient hyperphosphatasemia (TH) is a condition characterized by elevated serum alkaline phosphatase (ALP) in the clinical setting with no evidence of bone or liver disease among children under the age of 5. Typically, it will resolve spontaneously in a few months in the majority of cases. TH has been found to be associated with viral infections. Two cases of TH associated with coronavirus disease 2019 (COVID-19) infection in toddlers have been previously reported. CASE SUMMARY: A previously healthy 2-year-old boy presented with fever and positive real-time polymerase chain reaction for COVID-19. Prior to his illness, the patient had been in close contact with his grandfather, who later developed COVID-19. The physical examination on admission was unremarkable. He remained asymptomatic throughout 7 d of hospitalization. On the 5th day of his illness, blood tests showed markedly elevated serum ALP (4178 U/L). Results from the simultaneous testing of the remaining liver profiles and metabolic bone panels were normal. Two months after discharge from the hospital, the patient continued to thrive well. The skeletal surveys revealed no significant abnormalities. The serum ALP declined into the normal range adjusted for his age. This evidence is consistent with the diagnosis of TH. CONCLUSION: TH can occur in COVID-19-infected toddlers. Serial measurements of ALP levels have been shown to gradually decline into the normal range within a few months. Therefore, being aware of this transient abnormality will help clinicians to avoid additional unnecessary investigations.

Standard and high dose ergocalciferol regimens for treatment of hypovitaminosis D in epileptic children and adolescents.

OBJECTIVES: Children with epilepsy are at increased risk of vitamin D deficiency. We aimed to compare the effect of two ergocalciferol regimens given for 90 days. METHODS: Epileptic patients aged 5-18 years who received at least one antiepileptic drug (AED) for more than 6 months and had serum 25-OHD <30 ng/mL were randomized to receive 20,000 IU/10 d (standard dose, n=41) or 60,000 IU/10 d (high dose, n=41) of oral ergocalciferol. Serum Ca, P, Mg, ALP, iPTH and urine Ca/Cr ratio were measured at baseline and after 90 days of treatment. Change in serum 25-OHD and vitamin D status after treatment was evaluated. RESULTS: The initial serum 25-OHD in the standard dose and high dose group was 19.5 ± 4.9 and 18.4 ± 4.6 ng/mL, respectively. Serum 25-OHD after treatment was significantly higher in the high dose group (39.0 ± 11.5 vs. 27.5 ± 8.6 ng/mL, p<0.05). The average increase in serum 25-OHD in the high dose and standard dose group was 20.6 ± 11.4 and 7.2 ± 7.5 ng/mL, respectively (p<0.05). Normalized serum 25-OHD was achieved in 80.5% of the high dose group compared to 36.6% of the standard dose group (p<0.05). No adverse events were found. Patients with a BMI Z-score>0 had a 2.5 times greater risk of continued hypovitaminosis D after treatment compared to those with a BMI Z-score<0 (95% CI: 1.0-5.9, p<0.05). CONCLUSIONS: Oral ergocalciferol 60,000 IU/10 d for 90 days was more effective at normalizing serum 25-OHD than 20,000 IU/10 d in epileptic children and adolescents who were receiving AEDs.

Hypovitaminosis D and risk factors in pediatric epilepsy children.

BACKGROUND: Anti-seizure medication (ASM) treatment is one of the significant risk factors associated with abnormal vitamin D status in epilepsy patients. Multiple studies have shown that adult epilepsy patients can exhibit vitamin D deficiency. However, there are few reports investigating pediatric epilepsy patients. In this study, we aimed to identify risk factors related to hypovitaminosis D in pediatric epilepsy patients in Thailand. METHODS: A cross-sectional retrospective cohort study was conducted in 138 pediatric epilepsy patients who received anticonvulsants from April 2018 to January 2019. Demographic data, seizure types, puberty status, physical activity, duration, and types of anti-seizure medications were analyzed. Patients with abnormal liver function, abnormal renal function, and who received vitamin D supplements or ketogenic diet containing vitamin D were excluded. Levels of serum vitamin D (25(OH)D) were measured. RESULTS: All 138 subjects were enrolled, the age ranged from 1.04 - 19.96 years; (mean = 9.65 ± 5.09), the mean serum 25(OH) D level was 26.56 ± 9.67 ng/ml. The prevalence of vitamin D deficiency was 23.2% and insufficiency was 47.8% respectively. Two risk factors-puberty status (OR 5.43, 95% CI 1.879-15.67) and non-enzyme-inhibiting ASMs therapy (OR 3.58, 95% CI 1.117-11.46)-were significantly associated with hypovitaminosis D, as shown by multivariate analyses. CONCLUSIONS: Our study reports the high prevalence of hypovitaminosis D in pediatric epilepsy patients in Thailand despite being located in the tropical zone. These findings can guide clinicians to measure vitamin D status in pediatric epilepsy patients particularly when they reach puberty and/or are using non-enzyme-inhibiting ASMs therapy. Early detection of vitamin D status and prompt vitamin D supplementation can prevent fractures and osteoporosis later in life. TRIAL REGISTRATION: TCTR20210215005 ( http://www.clinicaltrials.in.th/ ).

Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9.

Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.9 (Nav1.9) established a distinctive CIP in three unrelated patients who suffered multiple painless fractures, self-inflicted mutilation, chronic diarrhea, and hyperhidrosis. Here, we studied a mother and two children with CIP by physical examination, biochemical testing, radiological imaging including DXA, iliac crest histology, and mutation analysis. She suffered fractures primarily of her lower extremities beginning at age two years, and had Charcot deformity of both ankles and joint hypermobility. Nerve conduction velocity together with electromyography were normal. Her children had recurrent major fractures beginning in early childhood, joint hypermobility, and chronic diarrhea. She had an excoriated external nare, and both children had hypertrophic scars from scratching. Skin collagen studies were normal. Radiographs revealed fractures and deformities. However, lumbar spine and total hip BMD Z-scores, biochemical parameters of mineral and skeletal homeostasis, and iliac crest histology of the mother (after in vivo tetracycline labeling) were normal. Genomic DNA from the children revealed a unique heterozygous missense mutation in exon 23 (c.3904C>T, p.Leu1302Phe) of SCN11A that is absent in SNP databases and alters an evolutionarily conserved amino acid. This autosomal dominant CIP reflects the second gain-of-function mutation of SCN11A. Perhaps joint hypermobility is an unreported feature. How mutation of Nav1.9 causes fracturing remains unexplained. Lack of injury awareness is typically offered as the reason, and was supported by our unremarkable biochemical, radiological, and histological findings indicating no skeletal pathobiology. However, low-trauma fracturing in these patients suggests an uncharacterized defect in bone quality.